A Study to Find Out How Nintedanib is Taken up in the Body and How Well it is Tolerated in Children and Adolescents With Interstitial Lung Disease (ILD) (InPedILD®)

• ClinicalTrials.gov Identifier: NCT04093024
• Recruitment Status: Completed
• First Posted: September 17, 2019
• Results First Posted: January 31, 2023
• Last Update Posted: April 25, 2023
• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Lung Diseases, Interstitial
• Interventions: Drug: Nintedanib; Drug: Placebo
• Enrollment: 39

Participant Flow

Recruitment Details

This was a multicenter, multinational, prospective clinical trial to evaluate the dose-exposure and safety of Nintedanib on top of standard of care (SOC) in children and adolescents (6 to 17 years old) with clinically significant fibrosing Interstitial Lung Disease (ILD) in two parts. A randomised, placebo-controlled, double-blind treatment period of 24 weeks (double-blind period (DBP)) was followed by an open-label Nintedanib period (OLNP)) of variable duration.

Pre-assignment Details

Only subjects that met all the study inclusion and none of the exclusion criteria were to be entered in the study. All participants were free to withdraw from the clinical trial at any time for any reason given. Close monitoring of all participants was adhered to throughout the trial conduct. Treatment interruption and dose reduction were allowed as medically indicated.

Arm/Group Title	DBP+OLNP: Randomised to Placebo	DBP+OLNP: Randomised to Nintedanib
Arm/Group Description	This arm shows placebo randomised participants treated orally with a Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Participants who continued with the open-label Nintedanib period (OLNP) after the DBP switched to active Nintedanib treatment in the OLNP and were treated orally with Nintedanib twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo first (DBP) and then Nintedanib (OLNP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP and OLNP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib in both periods (DBP + OLNP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.
Period Title: Double-blind Period
Started	13	26
Completed	11	21
Not Completed	2	5
Reason Not Completed
Completed prematurely due to administrative end of trial and did not continue with OLNP	2	2
Discontinued treatment due to adverse event	0	2
Discontinued treatment due to other reason	0	1
Period Title: Open-label Nintedanib Period (OLNP)
Started	11	21
Completed	11	20
Not Completed	0	1
Reason Not Completed
Discontinuation of trial medication due to other reason	0	1

Baseline Characteristics

Arm/Group Title		DBP+OLNP: Randomised to Placebo	DBP+OLNP: Randomised to Nintedanib	Total
Arm/Group Description		This arm shows placebo randomised participants treated orally with a Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Participants who continued with the open-label Nintedanib period (OLNP) after the DBP switched to active Nintedanib treatment in the OLNP and were treated orally with Nintedanib twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo first (DBP) and then Nintedanib (OLNP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP and OLNP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib in both periods (DBP + OLNP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.	Total of all reporting groups
Overall Number of Baseline Participants		13	26	39
Baseline Analysis Population Description		Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	13 participants	26 participants	39 participants
		12.9 (2.8)	12.5 (3.6)	12.6 (3.3)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	13 participants	26 participants	39 participants
	Female	5 38.5%	10 38.5%	15 38.5%
	Male	8 61.5%	16 61.5%	24 61.5%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	13 participants	26 participants	39 participants
	Hispanic or Latino	5 38.5%	7 26.9%	12 30.8%
	Not Hispanic or Latino	8 61.5%	18 69.2%	26 66.7%
	Unknown or Not Reported	0 0.0%	1 3.8%	1 2.6%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	13 participants	26 participants	39 participants
	American Indian or Alaska Native	1 7.7%	1 3.8%	2 5.1%
	Asian	0 0.0%	2 7.7%	2 5.1%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	3 11.5%	3 7.7%
	White	12 92.3%	19 73.1%	31 79.5%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	1 3.8%	1 2.6%

Outcome Measures

1. Primary Outcome

Title	Area Under the Plasma Concentration-time Curve at Steady State (AUCτ,ss) Based on Sampling at Steady State (at Week 2 and Week 26)
Description	Area under the plasma concentration-time curve at steady state (AUCt,ss) based on sampling at steady state (at Week 2 and Week 26) after multiple oral administration of Nintedanib by age group over all treatments. Values of samples taken at Week 2 (for randomised Nintedanib participants) and at Week 26 (for randomised placebo participants) were used. Missing values at Week 2 of randomised Nintedanib participants were replaced with values taken at Week 26.
Time Frame	At Week 2 and at Week 26: at 5 minutes before and at 0, 1, 2, 3, 4, 6, and 8 hours post administration of the morning dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic parameter analysis set (PKS):

This set includes all patients in the treated set (TS) who provide at least one pharmacokinetic (PK) endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability

Arm/Group Title	DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib	DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib
Arm/Group Description:	This arm shows participants aged 6 to < 12 years old who were exposed to Nintedanib only, either randomised placebo (treated with Nintedanib in the OLNP only) and randomised Nintedanib (treated with Nintedanib in both, DBP and OLNP). The 6 to < 12 years old participant were treated orally with Nintedanib twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib only (OLNP or DBP+OLNP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.	This arm shows participants aged 12 to <18 years old who were exposed to Nintedanib only either randomised placebo (treated with Nintedanib in the OLNP only) and randomised Nintedanib (treated with Nintedanib in both, DBP and OLNP). The 12 to 18 years old participant were treated orally with Nintedanib twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib only (OLNP or DBP+OLNP). Participants in this arm do not entail participants from the '6 to < 12 years - exposed to Nintedanib' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.
Overall Number of Participants Analyzed	10	23
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Hours times nanogram per mililiter
	175; (85.1%)	167; (83.6%)

2. Primary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events During the Double-blind Period
Description	Treatment-emergent was defined as: Adverse events with onset or worsening on or after date of treatment start until end of double-blind period (defined as the day before first intake of open-label nintedanib or last double-blind drug intake + residual effect period, whichever is earlier) were considered as treatment-emergent and were included in the analysis. Adverse events were counted under the treatment as randomized for the double-blind period.
Time Frame	From first drug administration until the earlier of (i) first intake of open-label nintedanib (exclusive) and (ii) last drug intake, up to 28 weeks

Outcome Measure Data

Analysis Population Description

Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication.

Arm/Group Title	DBP: Randomised to Placebo	DBP: Randomised to Nintedanib
Arm/Group Description:	This arm shows placebo randomised participants treated orally with a Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo only (DBP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib only (DBP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake.
Overall Number of Participants Analyzed	13	26
Measure Type: Count of Participants; Unit of Measure: Participants
	11 84.6%	22 84.6%

3. Secondary Outcome

Title	Number of Participants With at Least One Treatment-emergent Pathological Finding of Epiphyseal Growth Plate on Imaging up to Week 24, and Week 52
Description	Number of participants with at least one treatment-emergent pathological finding of the epiphyseal growth plate imaging (Magnetic Resonance Imaging (MRI)s/x-rays) were analyzed cumulatively and based on central review.
Time Frame	Up to Week 24 (included values at Week 12 and Week 24); Up to Week 52 (included values at Week 12, 24, 36 and 52)

Outcome Measure Data

Analysis Population Description

Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication.

Arm/Group Title	DBP+OLNP: Randomised to Placebo	DBP+OLNP: Randomised to Nintedanib
Arm/Group Description:	This arm shows placebo randomised participants treated orally with a Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Participants who continued with the open-label Nintedanib period (OLNP) after the DBP switched to active Nintedanib treatment in the OLNP and were treated orally with Nintedanib twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo first (DBP) and then Nintedanib (OLNP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP and OLNP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib in both periods (DBP + OLNP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.
Overall Number of Participants Analyzed	13	26
Measure Type: Count of Participants; Unit of Measure: Participants
At Week 24	1 7.7%	2 7.7%
At Week 52	2 15.4%	3 11.5%

4. Secondary Outcome

Title	Number of Participants With Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 24
Description	Number of participants with treatment-emergent pathological findings on dental examination (clinical examination) based on dentist assessment or imaging (panoramic x-ray) based on central review were analyzed. Number of participants with treatment-emergent pathological findings on dental imaging were analyzed cumulatively.
Time Frame	Dental examination: at Week 12 and Week 24; Dental imaging: at Week 24

Outcome Measure Data

Analysis Population Description

Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication.

Arm/Group Title	DBP: Randomised to Placebo	DBP: Randomised to Nintedanib
Arm/Group Description:	This arm shows placebo randomised participants treated orally with a Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo only (DBP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib only (DBP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake.
Overall Number of Participants Analyzed	13	26
Measure Type: Count of Participants; Unit of Measure: Participants
Dental examination: Pathological findings up to week 24	1 7.7%	5 19.2%
Dental imaging: Stunted growth of dental root	0 0.0%	6 23.1%
Dental imaging: Accelerated growth of dental root	0 0.0%	0 0.0%
Dental imaging: extra / supernumerary teeth	0 0.0%	0 0.0%
Dental imaging: Impacted permanent teeth	2 15.4%	4 15.4%
Dental imaging: Additional findings	1 7.7%	5 19.2%
Dental imaging: Other findings	2 15.4%	1 3.8%

5. Secondary Outcome

Title	Number of Participants With at Least One Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 52
Description	Number of participants with treatment-emergent pathological findings on dental examination (clinical examination) based on dentist assessment or imaging (panoramic x-ray) based on central review were analyzed. Number of participants with treatment-emergent pathological findings on dental imaging were analyzed cumulatively.
Time Frame	Dental examination: at Week 12, 24, 34, and Week 52; Dental imaging: at Week 24 and at Week 52.

Outcome Measure Data

Analysis Population Description

Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication.

Arm/Group Title	DBP+OLNP: Randomised to Placebo	DBP+OLNP: Randomised to Nintedanib
Arm/Group Description:	This arm shows placebo randomised participants treated orally with a Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Participants who continued with the open-label Nintedanib period (OLNP) after the DBP switched to active Nintedanib treatment in the OLNP and were treated orally with Nintedanib twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo first (DBP) and then Nintedanib (OLNP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP and OLNP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib in both periods (DBP + OLNP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.
Overall Number of Participants Analyzed	13	26
Measure Type: Count of Participants; Unit of Measure: Participants
Dental examination: Pathological findings up to week 52	3 23.1%	7 26.9%
Dental imaging: Stunted growth of dental root	0 0.0%	6 23.1%
Dental imaging: Accelerated growth of dental root	0 0.0%	0 0.0%
Dental imaging: extra / supernumerary teeth	0 0.0%	0 0.0%
Dental imaging: Impacted permanent teeth	2 15.4%	5 19.2%
Dental imaging: Additional findings	1 7.7%	6 23.1%
Dental imaging: Other findings	3 23.1%	2 7.7%

6. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events Over the Whole Trial
Description	Treatment-emergent was defined as: Adverse events with onset or worsening on or after date of treatment start until last drug intake + residual effect period was considered as treatment-emergent and was included in the analysis. Adverse events were counted under the treatment as randomized for the double-blind period.
Time Frame	From first drug administration until the last drug intake, up to 92 weeks

Outcome Measure Data

Analysis Population Description

Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication.

Arm/Group Title	DBP: Randomised to Placebo	OLNP: Randomised to Placebo and Switched to Nintedanib	DBP+OLNP: Randomised to Nintedanib
Arm/Group Description:	This arm shows placebo randomised participants treated orally with a Nintedanib matching soft capsules twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP) up to week 24. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo only (DBP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake.	This arm shows participants who continued with the open-label Nintedanib period (OLNP) after the DBP, switched to active Nintedanib treatment in the OLNP and were treated orally with Nintedanib twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib only (OLNP). OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP and OLNP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib in both periods (DBP + OLNP). Participants in this arm do not entail participants from the 'randomised to placebo' arms. DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.
Overall Number of Participants Analyzed	13	11	26
Measure Type: Count of Participants; Unit of Measure: Participants
	11 84.6%	11 100.0%	26 100.0%

7. Secondary Outcome

Title	Absolute Change From Baseline in Height at Week 24
Description	Absolute change from baseline in height at Week 24 was measured with a stadiometer 3 times at each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in height at Week 24 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time Frame	MMRM included measurements pre-administration at -4 weeks and at 0, 12, 24, 36, 52, 64, 76, and 88 weeks after first drug administration. MMRM values at Week 24 are reported in the table below

Outcome Measure Data

Analysis Population Description

Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.

Arm/Group Title	DBP: Randomised to Placebo	DBP: Randomised to Nintedanib
Arm/Group Description:	This arm shows placebo randomised participants treated orally with a Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo only (DBP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib only (DBP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake.
Overall Number of Participants Analyzed	13	25
Least Squares Mean (95% Confidence Interval); Unit of Measure: Centimeter
	1.3; (0.6 to 1.9)	1.3; (0.8 to 1.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBP: Randomised to Placebo, DBP: Randomised to Nintedanib
	Comments	No formal hypotheses were tested
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9858
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measures (MMRM)
	Comments	Fixed categorical effects: (Randomised) treatment, age-group; Fixed continuous effects: Baseline at each visit, random effect for participant.
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.8 to 0.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.4
	Estimation Comments	Adjusted mean difference was calculated as 'Randomised Nintedanib - randomised placebo'.

8. Secondary Outcome

Title	Absolute Change From Baseline in Height at Week 52
Description	Absolute change from baseline in height at Week 52 was measured with a stadiometer 3 times at each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in height at Week 52 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time Frame	MMRM included measurements pre-administration at -4 weeks and at 0, 12, 24, 36, 52, 64, 76, and 88 weeks after first drug administration. MMRM values at Week 52 are reported in the table below

Outcome Measure Data

Analysis Population Description

Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.

Arm/Group Title	DBP+OLNP: Randomised to Placebo	DBP+OLNP: Randomised to Nintedanib
Arm/Group Description:	This arm shows placebo randomised participants treated orally with a Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Participants who continued with the open-label Nintedanib period (OLNP) after the DBP switched to active Nintedanib treatment in the OLNP and were treated orally with Nintedanib twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo first (DBP) and then Nintedanib (OLNP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP and OLNP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib only (DBP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.
Overall Number of Participants Analyzed	13	25
Least Squares Mean (95% Confidence Interval); Unit of Measure: Centimeter
	2.8; (1.5 to 4.2)	2.8; (1.8 to 3.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBP+OLNP: Randomised to Placebo, DBP+OLNP: Randomised to Nintedanib
	Comments	No formal hypotheses were tested
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9769
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measures (MMRM)
	Comments	Fixed categorical effects: (Randomised) treatment, age-group; Fixed continuous effects: Baseline at each visit, random effect for participant.
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.0
	Confidence Interval	(2-Sided) 95%; -1.7 to 1.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.8
	Estimation Comments	Adjusted mean difference was calculated as 'Randomised Nintedanib - randomised placebo'.

9. Secondary Outcome

Title	Absolute Change From Baseline in Height at Week 76
Description	Absolute change from baseline in height at Week 76 was measured with a stadiometer 3 times at each time point. The average of these 3 measurements was taken per time point. MMRM has been calculated but did not provide estimates for this time point due to low sample size. Thus, change in height from baseline to Week 76 was analyzed descriptively only.
Time Frame	Measurements were assessed at Week 0 and at Week 76

Outcome Measure Data

Analysis Population Description

Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.

Arm/Group Title	DBP+OLNP: Randomised to Placebo	DBP+OLNP: Randomised to Nintedanib
Arm/Group Description:	This arm shows placebo randomised participants treated orally with a Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Participants who continued with the open-label Nintedanib period (OLNP) after the DBP switched to active Nintedanib treatment in the OLNP and were treated orally with Nintedanib twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo first (DBP) and then Nintedanib (OLNP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP and OLNP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib in both periods (DBP + OLNP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.
Overall Number of Participants Analyzed	3	4
Mean (Standard Deviation); Unit of Measure: Centimeter
At Baseline	143.7 (11.2)	162.5 (15.8)
At Week 76	150.0 (15.7)	165.5 (13.0)

10. Secondary Outcome

Title	Absolute Change From Baseline in Sitting Height at Week 24
Description	Absolute change from baseline in sitting height at Week 24 was measured with a stadiometer 3 times at each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in sitting height at Week 24 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time Frame	MMRM included measurements pre-administration at -4 weeks and at 0, 12, 24, 36, 52, 64, 76, and 88 weeks after first drug administration. MMRM values at Week 24 are reported in the table below.

Outcome Measure Data

Analysis Population Description

Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.

Arm/Group Title	DBP: Randomised to Placebo	DBP: Randomised to Nintedanib
Arm/Group Description:	This arm shows placebo randomised participants treated orally with a Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo only (DBP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib only (DBP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake.
Overall Number of Participants Analyzed	6	15
Least Squares Mean (95% Confidence Interval); Unit of Measure: Centimeters
	1.0; (-1.3 to 3.4)	2.1; (0.6 to 3.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBP: Randomised to Placebo, DBP: Randomised to Nintedanib
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	No formal hypotheses were tested
Statistical Test of Hypothesis	P-Value	0.4442
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measures (MMRM)
	Comments	Fixed categorical effects: (Randomised) treatment, age-group; Fixed continuous effects: Baseline at each visit, random effect for participant.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	1.1
	Confidence Interval	(2-Sided) 95%; -1.8 to 4.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.4
	Estimation Comments	Adjusted mean difference was calculated as 'Randomised Nintedanib - randomised placebo'.

11. Secondary Outcome

Title	Absolute Change From Baseline in Sitting Height at Week 52
Description	Absolute change from baseline in sitting height at Week 52 was measured with a stadiometer 3 times at each time point. The average of these 3 measurements was taken per time point. MMRM has been calculated but did not provide estimates for this time point due to low sample size. Thus, change in sitting height from baseline to Week 52 was analyzed descriptively only.
Time Frame	Measurements were assessed at Week 0 and at Week 52

Outcome Measure Data

Analysis Population Description

Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with non-missing results were included in the analysis.

Arm/Group Title	DBP + OLNP: Randomised to Placebo	DBP + OLNP: Randomised to Nintedanib
Arm/Group Description:	This arm shows placebo randomised participants treated orally with a Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Participants who continued with the open-label Nintedanib period (OLNP) after the DBP switched to active Nintedanib treatment in the OLNP and were treated orally with Nintedanib twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo first (DBP) and then Nintedanib (OLNP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP and OLNP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib in both periods (DBP + OLNP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.
Overall Number of Participants Analyzed	3	7
Mean (Standard Deviation); Unit of Measure: Centimeters
At Baseline	78.7 (11.8)	77.6 (9.4)
At Week 52	79.0 (12.2)	79.3 (8.6)

12. Secondary Outcome

Title	Absolute Change From Baseline in Sitting Height at Week 76
Description	Absolute change from baseline in sitting height at Week 76 was measured with a stadiometer 3 times at each time point. The average of these 3 measurements was take per time point. MMRM has been calculated but did not provide estimates for this time point due to low sample size. Thus, change in sitting height from baseline to Week 76 was analyzed descriptively only.
Time Frame	Measurements were assessed at Week 0 and at Week 76

Outcome Measure Data

Analysis Population Description

Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with non-missing results were included in the analysis.

Arm/Group Title	DBP + OLNP: Randomised to Placebo	DBP+OLNP: Randomised to Nintedanib
Arm/Group Description:	This arm shows placebo randomised participants treated orally with a Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Participants who continued with the open-label Nintedanib period (OLNP) after the DBP switched to active Nintedanib treatment in the OLNP and were treated orally with Nintedanib twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo first (DBP) and then Nintedanib (OLNP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP and OLNP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib in both periods (DBP + OLNP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.
Overall Number of Participants Analyzed	1	2
Mean (Standard Deviation); Unit of Measure: Centimeters
At Baseline	65.0 [1] (NA)	83.0 (4.2)
At Week 76	65.0 [1] (NA)	84.5 (3.5)

[1]

One participant is not sufficient to calculate a standard deviation.

13. Secondary Outcome

Title	Absolute Change From Baseline in Leg Length at Week 24 - Left
Description	Absolute change from baseline in left leg length at Week 24 was assessed by measuring the distance between the anterior iliac spine and the medial malleolus 3 times at each leg and each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in left leg length at Week 24 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time Frame	MMRM included measurements at 0, 12, 24, 36, 52, 64, and 76 weeks after first drug administration. MMRM values at Week 24 are reported in the table below

Outcome Measure Data

Analysis Population Description

Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.

Arm/Group Title	DBP: Randomised to Placebo	DBP: Randomised to Nintedanib
Arm/Group Description:	This arm shows placebo randomised participants treated orally with a Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo only (DBP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib only (DBP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake.
Overall Number of Participants Analyzed	13	23
Least Squares Mean (95% Confidence Interval); Unit of Measure: Centimeters
	1.6; (0.3 to 2.9)	1.7; (0.8 to 2.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBP: Randomised to Placebo, DBP: Randomised to Nintedanib
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	No formal hypotheses were tested
Statistical Test of Hypothesis	P-Value	0.8820
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measures (MMRM)
	Comments	Fixed categorical effects: (Randomised) treatment, age-group; Fixed continuous effects: Baseline at each visit, random effect for participant.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -1.5 to 1.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.8
	Estimation Comments	Adjusted mean difference was calculated as 'Randomised Nintedanib - randomised placebo'.

14. Secondary Outcome

Title	Absolute Change From Baseline in Leg Length at Week 52 - Left
Description	Absolute change from baseline in left leg length at Week 52 was assessed by measuring the distance between the anterior iliac spine and the medial malleolus 3 times at each leg and each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in left leg length at Week 52 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time Frame	MMRM included measurements at 0, 12, 24, 36, 52, 64, and 76 weeks after first drug administration. MMRM values at Week 52 are reported in the table below

Outcome Measure Data

Analysis Population Description

Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.

Arm/Group Title	DBP+OLNP: Randomised to Placebo	DBP+OLNP: Randomised to Nintedanib
Arm/Group Description:	This arm shows placebo randomised participants treated orally with a Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Participants who continued with the open-label Nintedanib period (OLNP) after the DBP switched to active Nintedanib treatment in the OLNP and were treated orally with Nintedanib twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo first (DBP) and then Nintedanib (OLNP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP and OLNP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib in both periods (DBP + OLNP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.
Overall Number of Participants Analyzed	13	23
Least Squares Mean (95% Confidence Interval); Unit of Measure: Centimeter
	2.8; (0.3 to 5.4)	2.9; (0.9 to 4.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBP+OLNP: Randomised to Placebo, DBP+OLNP: Randomised to Nintedanib
	Comments	No formal hypotheses were tested
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9652
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measures (MMRM)
	Comments	Fixed categorical effects: (Randomised) treatment, age-group; Fixed continuous effects: Baseline at each visit, random effect for participant.
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -3.2 to 3.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.6
	Estimation Comments	Adjusted mean difference was calculated as 'Randomised Nintedanib - randomised placebo'.

15. Secondary Outcome

Title	Absolute Change From Baseline in Leg Length at Week 76 - Left
Description	Absolute change from baseline in left leg length at Week 76 was assessed by measuring the distance between the anterior iliac spine and the medial malleolus 3 times at each leg and each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in left leg length at Week 76 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time Frame	MMRM included measurements at 0, 12, 24, 36, 52, 64, and 76 weeks after first drug administration. MMRM values at Week 76 are reported in the table below

Outcome Measure Data

Analysis Population Description

Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.

Arm/Group Title	DBP+OLNP: Randomised to Placebo	DBP+OLNP: Randomised to Nintedanib
Arm/Group Description:	This arm shows placebo randomised participants treated orally with a Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Participants who continued with the open-label Nintedanib period (OLNP) after the DBP switched to active Nintedanib treatment in the OLNP and were treated orally with Nintedanib twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo first (DBP) and then Nintedanib (OLNP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP and OLNP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib in both periods (DBP + OLNP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.
Overall Number of Participants Analyzed	13	23
Least Squares Mean (95% Confidence Interval); Unit of Measure: Centimeter
	5.2; (-0.0 to 10.5)	2.6; (-1.5 to 6.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBP+OLNP: Randomised to Placebo, DBP+OLNP: Randomised to Nintedanib
	Comments	No formal hypotheses were tested
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4084
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measures (MMRM)
	Comments	Fixed categorical effects: (Randomised) treatment, age-group; Fixed continuous effects: Baseline at each visit, random effect for participant.
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-2.6
	Confidence Interval	(2-Sided) 95%; -9.3 to 4.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.1
	Estimation Comments	Adjusted mean difference was calculated as 'Randomised Nintedanib - randomised placebo'.

16. Secondary Outcome

Title	Absolute Change From Baseline in Leg Length at Week 24 - Right
Description	Absolute change from baseline in right leg length at Week 24 was assessed by measuring the distance between the anterior iliac spine and the medial malleolus 3 times at each leg and each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in right leg length at Week 24 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time Frame	MMRM included measurements at 0, 12, 24, 36, 52, 64, and 76 weeks after first drug administration. MMRM values at Week 24 are reported in the table below

Outcome Measure Data

Analysis Population Description

Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.

Arm/Group Title	DBP: Randomised to Placebo	DBP: Randomised to Nintedanib
Arm/Group Description:	This arm shows placebo randomised participants treated orally with a Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo only (DBP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib only (DBP). Participants in this arm do not entail participants from the 'randomised to placebo' arms. DBP: Planned was from first randomised trial drug intake to last blinded drug intake.
Overall Number of Participants Analyzed	13	23
Least Squares Mean (95% Confidence Interval); Unit of Measure: Centimeters
	1.6; (0.3 to 2.9)	1.6; (0.6 to 2.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBP: Randomised to Placebo, DBP: Randomised to Nintedanib
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	No formal hypotheses were tested
Statistical Test of Hypothesis	P-Value	0.9928
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measures (MMRM)
	Comments	Fixed categorical effects: (Randomised) treatment, age-group; Fixed continuous effects: Baseline at each visit, random effect for participant.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -1.6 to 1.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.8
	Estimation Comments	Adjusted mean difference was calculated as 'Randomised Nintedanib - randomised placebo'.

17. Secondary Outcome

Title	Absolute Change From Baseline in Leg Length at Week 52 - Right
Description	Absolute change from baseline in right leg length at Week 52 was assessed by measuring the distance between the anterior iliac spine and the medial malleolus 3 times at each leg and each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in right leg length at Week 52 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time Frame	MMRM included measurements at 0, 12, 24, 36, 52, 64, and 76 weeks after first drug administration. MMRM values at Week 52 are reported in the table below

Outcome Measure Data

Analysis Population Description

Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.

Arm/Group Title	DBP+OLNP: Randomised to Placebo	DBP+OLNP: Randomised to Nintedanib
Arm/Group Description:	This arm shows placebo randomised participants treated orally with a Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Participants who continued with the open-label Nintedanib period (OLNP) after the DBP switched to active Nintedanib treatment in the OLNP and were treated orally with Nintedanib twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo first (DBP) and then Nintedanib (OLNP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP and OLNP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib in both periods (DBP + OLNP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.
Overall Number of Participants Analyzed	13	23
Least Squares Mean (95% Confidence Interval); Unit of Measure: Centimeter
	2.8; (0.4 to 5.1)	3.4; (1.6 to 5.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBP+OLNP: Randomised to Placebo, DBP+OLNP: Randomised to Nintedanib
	Comments	No formal hypotheses were tested
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6366
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measures (MMRM)
	Comments	Fixed categorical effects: (Randomised) treatment, age-group; Fixed continuous effects: Baseline at each visit, random effect for participant.
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	0.7
	Confidence Interval	(2-Sided) 95%; -2.3 to 3.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.4
	Estimation Comments	Adjusted mean difference was calculated as 'Randomised Nintedanib - randomised placebo'.

18. Secondary Outcome

Title	Absolute Change From Baseline in Leg Length at Week 76 - Right
Description	Absolute change from baseline in right leg length at Week 76 was assessed by measuring the distance between the anterior iliac spine and the medial malleolus 3 times at each leg and each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in right leg length at Week 76 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time Frame	MMRM included measurements at 0, 12, 24, 36, 52, 64, and 76 weeks after first drug administration. MMRM values at Week 76 are reported in the table below

Outcome Measure Data

Analysis Population Description

Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.

Arm/Group Title	DBP+OLNP: Randomised to Placebo	DBP+OLNP: Randomised to Nintedanib
Arm/Group Description:	This arm shows placebo randomised participants treated orally with a Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Participants who continued with the open-label Nintedanib period (OLNP) after the DBP switched to active Nintedanib treatment in the OLNP and were treated orally with Nintedanib twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo first (DBP) and then Nintedanib (OLNP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP and OLNP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib in both periods (DBP + OLNP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.
Overall Number of Participants Analyzed	13	23
Least Squares Mean (95% Confidence Interval); Unit of Measure: Centimeter
	3.9; (-0.5 to 8.3)	4.3; (0.8 to 7.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBP+OLNP: Randomised to Placebo, DBP+OLNP: Randomised to Nintedanib
	Comments	No formal hypotheses were tested
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.8823
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measures (MMRM)
	Comments	Fixed categorical effects: (Randomised) treatment, age-group; Fixed continuous effects: Baseline at each visit, random effect for participant.
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -5.2 to 5.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.3
	Estimation Comments	Adjusted mean difference was calculated as 'Randomised Nintedanib - randomised placebo'.

19. Secondary Outcome

Title	Absolute Change From Baseline in Forced Vital Capacity (FVC) % Predicted at Week 24
Description	Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. The predicted values were calculated according to the Global Lungs Initiative (GLI) 2012 equations. Absolute change from baseline in Forced Vital Capacity (FVC) % predicted at Week 24 in the treated set(TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time Frame	MMRM included measurements pre-administration at -4 weeks and at 0, 2, 6, 12, 24, 26, 36, and 52 weeks after first drug administration. MMRM values at Week 24 are reported in the table below

Outcome Measure Data

Analysis Population Description

Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.

Arm/Group Title	DBP: Randomised to Placebo	DBP: Randomised to Nintedanib
Arm/Group Description:	This arm shows placebo randomised participants treated orally with a Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo only (DBP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP and OLNP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib only (DBP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake.
Overall Number of Participants Analyzed	13	26
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percentage of predicted FVC
	-0.8939; (-4.6090 to 2.8211)	0.3112; (-2.3595 to 2.9820)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBP: Randomised to Placebo, DBP: Randomised to Nintedanib
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	No formal hypotheses were tested
Statistical Test of Hypothesis	P-Value	0.5962
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measures (MMRM)
	Comments	Fixed categorical effects: (Randomised) treatment, age-group; Fixed continuous effects: Baseline at each visit, random effect for participant.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	1.2052
	Confidence Interval	(2-Sided) 95%; -3.3966 to 5.8070
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.2491
	Estimation Comments	Adjusted mean difference was calculated as 'Randomised Nintedanib - randomised placebo'.

20. Secondary Outcome

Title	Absolute Change From Baseline in Forced Vital Capacity (FVC) % Predicted at Week 52
Description	Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. The predicted values were calculated according to the Global Lungs Initiative (GLI) 2012 equations. Absolute change from baseline in Forced Vital Capacity (FVC) % predicted at Week 52 in the treated set(TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time Frame	MMRM included measurements pre-administration at -4 weeks and at 0, 2, 6, 12, 24, 26, 36, and 52 weeks after first drug administration. MMRM values at Week 52 are reported in the table below

Outcome Measure Data

Analysis Population Description

Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.

Arm/Group Title	DBP+OLNP: Randomised to Placebo	DBP + OLNP: Randomised to Nintedanib
Arm/Group Description:	This arm shows placebo randomised participants treated orally with a Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Participants who continued with the open-label Nintedanib period (OLNP) after the DBP switched to active Nintedanib treatment in the OLNP and were treated orally with Nintedanib twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo first (DBP) and then Nintedanib (OLNP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP and OLNP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib in both periods (DBP + OLNP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.
Overall Number of Participants Analyzed	13	26
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percentage of predicted FVC
	-0.9827; (-6.2611 to 4.2958)	0.7906; (-2.9464 to 4.5277)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBP+OLNP: Randomised to Placebo, DBP + OLNP: Randomised to Nintedanib
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	No formal hypotheses were tested
Statistical Test of Hypothesis	P-Value	0.5776
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measures (MMRM)
	Comments	Fixed categorical effects: (Randomised) treatment, age-group; Fixed continuous effects: Baseline at each visit, random effect for participant.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	1.7733
	Confidence Interval	(2-Sided) 95%; -4.7015 to 8.2481
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.1424
	Estimation Comments	Adjusted mean difference was calculated as 'Randomised Nintedanib - randomised placebo'.

21. Secondary Outcome

Title	Absolute Change From Baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at Week 24 - Parent Report
Description	The PedsQL™ questionnaires consists of 23 items (i) and 4 dimensions: physical (8i), emotional (5i), social (5i) and school (5i) functioning. A 5-point Likert response scale (0 = never (worst outcome) to 4=almost always (best outcome)) was used except for the Young Child Report, where a 3-point scale (0=not at all (worst outcome) to 4=a lot (best outcome)) was used. Items were reverse-scored and linearly transformed to a 0-100 scale (0 = 100 to 4 = 0). Higher scores indicated better health-related quality of life. To create total scores, the mean was computed. Absolute change from baseline in PedsQL™ reported by parents was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time Frame	MMRM included measurements at 0, 24, and 52 weeks after first drug administration. MMRM values at Week 24 are reported in the table below

Outcome Measure Data

Analysis Population Description

Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.

Arm/Group Title	DBP: Randomised to Placebo	DBP: Randomised to Nintedanib
Arm/Group Description:	This arm shows placebo randomised participants treated orally with a Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo only (DBP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib only (DBP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake.
Overall Number of Participants Analyzed	11	21
Least Squares Mean (95% Confidence Interval); Unit of Measure: Unit on scale
	5.615; (-1.506 to 12.736)	5.481; (0.384 to 10.578)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBP: Randomised to Placebo, DBP: Randomised to Nintedanib
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	No formal hypotheses were tested
Statistical Test of Hypothesis	P-Value	0.9755
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measures (MMRM)
	Comments	Fixed categorical effects: (Randomised) treatment, age-group; Fixed continuous effects: Baseline at each visit, random effect for participant.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-0.134
	Confidence Interval	(2-Sided) 95%; -8.975 to 8.707
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.316
	Estimation Comments	Adjusted mean difference was calculated as 'Randomised Nintedanib - randomised placebo'.

22. Secondary Outcome

Title	Absolute Change From Baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at Week 52 - Parent Report
Description	The PedsQL™ questionnaires consists of 23 items (i) and 4 dimensions: physical (8i), emotional (5i), social (5i) and school (5i) functioning. A 5-point Likert response scale (0 = never (worst outcome) to 4=almost always (best outcome)) was used except for the Young Child Report, where a 3-point scale (0=not at all (worst outcome) to 4=a lot (best outcome)) was used. Items were reverse-scored and linearly transformed to a 0-100 scale (0 = 100 to 4 = 0). Higher scores indicated better health-related quality of life. To create total scores, the mean was computed. Absolute change from baseline in PedsQL™ reported by parents was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time Frame	MMRM included measurements at 0, 24, and 52 weeks after first drug administration. MMRM values at Week 52 are reported in the table below

Outcome Measure Data

Analysis Population Description

Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.

Arm/Group Title	DBP+OLNP: Randomised to Placebo	DBP+OLNP: Randomised to Nintedanib
Arm/Group Description:	This arm shows placebo randomised participants treated orally with a Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Participants who continued with the open-label Nintedanib period (OLNP) after the DBP switched to active Nintedanib treatment in the OLNP and were treated orally with Nintedanib twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo first (DBP) and then Nintedanib (OLNP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP and OLNP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib in both periods (DBP + OLNP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.
Overall Number of Participants Analyzed	11	21
Least Squares Mean (95% Confidence Interval); Unit of Measure: Unit on scale
	4.377; (-4.403 to 13.157)	7.830; (1.799 to 13.862)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBP+OLNP: Randomised to Placebo, DBP+OLNP: Randomised to Nintedanib
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	No formal hypotheses were tested
Statistical Test of Hypothesis	P-Value	0.5140
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measures (MMRM)
	Comments	Fixed categorical effects: (Randomised) treatment, age-group; Fixed continuous effects: Baseline at each visit, random effect for participant.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	3.453
	Confidence Interval	(2-Sided) 95%; -7.250 to 14.157
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.225
	Estimation Comments	Adjusted mean difference was calculated as 'Randomised Nintedanib - randomised placebo'.

23. Secondary Outcome

Title	Absolute Change From Baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at Week 24 - Participant Report
Description	The PedsQL™ questionnaires consists of 23 items (i) and 4 dimensions: physical (8i), emotional (5i), social (5i) and school (5i) functioning. A 5-point Likert response scale (0 = never (worst outcome) to 4=almost always (best outcome)) was used except for the Young Child Report, where a 3-point scale (0=not at all (worst outcome) to 4=a lot (best outcome)) was used. Items were reverse-scored and linearly transformed to a 0-100 scale (0 = 100 to 4 = 0). Higher scores indicated better health-related quality of life. To create total scores, the mean was computed. Absolute change from baseline in PedsQL™ was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time Frame	MMRM included measurements at 0, 24, and 52 weeks after first drug administration. MMRM values at Week 24 are reported in the table below

Outcome Measure Data

Analysis Population Description

Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.

Arm/Group Title	DBP: Randomised to Placebo	DBP: Randomised to Nintedanib
Arm/Group Description:	This arm shows placebo randomised participants treated orally with a Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo only (DBP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib only (DBP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake.
Overall Number of Participants Analyzed	11	21
Least Squares Mean (95% Confidence Interval); Unit of Measure: Unit on scale
	5.484; (-0.051 to 11.018)	6.514; (2.531 to 10.497)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBP: Randomised to Placebo, DBP: Randomised to Nintedanib
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	No formal hypotheses were tested
Statistical Test of Hypothesis	P-Value	0.7613
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measures (MMRM)
	Comments	Fixed categorical effects: (Randomised) treatment, age-group; Fixed continuous effects: Baseline at each visit, random effect for participant.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	1.030
	Confidence Interval	(2-Sided) 95%; -5.848 to 7.908
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.358
	Estimation Comments	Adjusted mean difference was calculated as 'Randomised Nintedanib - randomised placebo'.

24. Secondary Outcome

Title	Absolute Change From Baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at Week 52 - Participant Report
Description	The PedsQL™ questionnaires consists of 23 items (i) and 4 dimensions: physical (8i), emotional (5i), social (5i) and school (5i) functioning. A 5-point Likert response scale (0 = never (worst outcome) to 4=almost always (best outcome)) was used except for the Young Child Report, where a 3-point scale (0=not at all (worst outcome) to 4=a lot (best outcome)) was used. Items were reverse-scored and linearly transformed to a 0-100 scale (0 = 100 to 4 = 0). Higher scores indicated better health-related quality of life. To create total scores, the mean was computed. Absolute change from baseline in PedsQL™ was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time Frame	MMRM included measurements at 0, 24, and 52 weeks after first drug administration. MMRM values at Week 52 are reported in the table below

Outcome Measure Data

Analysis Population Description

Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.

Arm/Group Title	DBP+OLNP: Randomised to Placebo	DBP+OLNP: Randomised to Nintedanib
Arm/Group Description:	This arm shows placebo randomised participants treated orally with a Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Participants who continued with the open-label Nintedanib period (OLNP) after the DBP switched to active Nintedanib treatment in the OLNP and were treated orally with Nintedanib twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo first (DBP) and then Nintedanib (OLNP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP and OLNP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib in both periods (DBP + OLNP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.
Overall Number of Participants Analyzed	11	21
Least Squares Mean (95% Confidence Interval); Unit of Measure: Unit on scale
	0.902; (-7.616 to 9.420)	1.243; (-4.598 to 7.083)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBP+OLNP: Randomised to Placebo, DBP+OLNP: Randomised to Nintedanib
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	No formal hypotheses were tested
Statistical Test of Hypothesis	P-Value	0.9468
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measures (MMRM)
	Comments	Fixed categorical effects: (Randomised) treatment, age-group; Fixed continuous effects: Baseline at each visit, random effect for participant.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	0.340
	Confidence Interval	(2-Sided) 95%; -10.026 to 10.707
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.049
	Estimation Comments	Adjusted mean difference was calculated as 'Randomised Nintedanib - randomised placebo'.

25. Secondary Outcome

Title	Absolute Change From Baseline in Oxygen Saturation (SpO₂) on Room Air at Rest at Week 24
Description	Oxygen saturation (SpO₂) was measured after minimum 5 minutes on room air by standard pulse oximetry at rest. Absolute change from baseline in SpO₂ at Week 24 in the treated set(TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time Frame	MMRM included measurements pre-administration at -4 weeks and at 0, 2, 6, 12, 24, 26, 36, and 52 weeks after first drug administration. MMRM values at Week 24 are reported in the table below

Outcome Measure Data

Analysis Population Description

Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.

Arm/Group Title	DBP: Randomised to Placebo	DBP: Randomised to Nintedanib
Arm/Group Description:	This arm shows placebo randomised participants treated orally with a Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo only (DBP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib only (DBP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake.
Overall Number of Participants Analyzed	13	26
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percentage of SpO₂
	-2.25; (-4.45 to -0.04)	0.07; (-1.49 to 1.63)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBP: Randomised to Placebo, DBP: Randomised to Nintedanib
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	No formal hypotheses were tested
Statistical Test of Hypothesis	P-Value	0.0908
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measures (MMRM)
	Comments	Fixed categorical effects: (Randomised) treatment, age-group; Fixed continuous effects: Baseline at each visit, random effect for participant.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	2.31
	Confidence Interval	(2-Sided) 95%; -0.39 to 5.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.33
	Estimation Comments	Adjusted mean difference was calculated as 'Randomised Nintedanib - randomised placebo'.

26. Secondary Outcome

Title	Absolute Change From Baseline in Oxygen Saturation (SpO₂) on Room Air at Rest at Week 52
Description	Oxygen saturation (SpO₂) was measured after minimum 5 minutes on room air by standard pulse oximetry at rest. Absolute change from baseline in SpO₂ at Week 52 in the treated set(TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time Frame	MMRM included measurements pre-administration at -4 weeks and at 0, 2, 6, 12, 24, 26, 36, and 52 weeks after first drug administration. MMRM values at Week 52 are reported in the table below

Outcome Measure Data

Analysis Population Description

Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.

Arm/Group Title	DBP+OLNP: Randomised to Placebo	DBP+OLNP: Randomised to Nintedanib
Arm/Group Description:	This arm shows placebo randomised participants treated orally with a Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Participants who continued with the open-label Nintedanib period (OLNP) after the DBP switched to active Nintedanib treatment in the OLNP and were treated orally with Nintedanib twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo first (DBP) and then Nintedanib (OLNP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP and OLNP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib in both periods (DBP + OLNP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.
Overall Number of Participants Analyzed	13	26
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percentage of SpO₂
	-2.60; (-5.02 to -0.18)	-0.32; (-2.03 to 1.40)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBP+OLNP: Randomised to Placebo, DBP+OLNP: Randomised to Nintedanib
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	No formal hypotheses were tested
Statistical Test of Hypothesis	P-Value	0.1222
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measures (MMRM)
	Comments	Fixed categorical effects: (Randomised) treatment, age-group; Fixed continuous effects: Baseline at each visit, random effect for participant.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	2.28
	Confidence Interval	(2-Sided) 95%; -0.69 to 5.25
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.39
	Estimation Comments	Adjusted mean difference was calculated as 'Randomised Nintedanib - randomised placebo'.

27. Secondary Outcome

Title	Absolute Change From Baseline in 6 Minutes (Min) Walk Distance at Week 24
Description	Absolute change from baseline in 6 minutes (min) walk distance at Week 24 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time Frame	MMRM included measurements at 0, 24, and 52 weeks after first drug administration. MMRM values at Week 24 are reported in the table below

Outcome Measure Data

Analysis Population Description

Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.

Arm/Group Title	DBP: Randomised to Placebo	DBP: Randomised to Nintedanib
Arm/Group Description:	This arm shows placebo randomised participants treated orally with a Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo only (DBP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib only (DBP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake.
Overall Number of Participants Analyzed	11	21
Least Squares Mean (95% Confidence Interval); Unit of Measure: Meter
	10.5; (-36.4 to 57.3)	17.6; (-16.2 to 51.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBP: Randomised to Placebo, DBP: Randomised to Nintedanib
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	No formal hypotheses were tested
Statistical Test of Hypothesis	P-Value	0.8012
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measures (MMRM)
	Comments	Fixed categorical effects: (Randomised) treatment, age-group; Fixed continuous effects: Baseline at each visit, random effect for participant.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	7.2
	Confidence Interval	(2-Sided) 95%; -50.7 to 65.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 28.2
	Estimation Comments	Adjusted mean difference was calculated as 'Randomised Nintedanib - randomised placebo'.

28. Secondary Outcome

Title	Absolute Change From Baseline in 6 Minutes (Min) Walk Distance at Week 52
Description	Absolute change from baseline in 6 minutes (min) walk distance at Week 52 in the treated set(TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time Frame	MMRM included measurements at 0, 24, and 52 weeks after first drug administration. MMRM values at Week 52 are reported in the table below

Outcome Measure Data

Analysis Population Description

Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.

Arm/Group Title	DBP+OLNP: Randomised to Placebo	DBP+OLNP: Randomised Nintedanib
Arm/Group Description:	This arm shows placebo randomised participants treated orally with a Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Participants who continued with the open-label Nintedanib period (OLNP) after the DBP switched to active Nintedanib treatment in the OLNP and were treated orally with Nintedanib twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo first (DBP) and then Nintedanib (OLNP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP and OLNP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib in both periods (DBP + OLNP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake, up to 24 weeks. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.
Overall Number of Participants Analyzed	11	21
Least Squares Mean (95% Confidence Interval); Unit of Measure: Meter (m)
	28.1; (-29.4 to 85.5)	-4.9; (-44.5 to 34.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBP+OLNP: Randomised to Placebo, DBP+OLNP: Randomised Nintedanib
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	No formal hypotheses were tested
Statistical Test of Hypothesis	P-Value	0.3401
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measures (MMRM)
	Comments	Fixed categorical effects: (Randomised) treatment, age-group; Fixed continuous effects: Baseline at each visit, random effect for participant.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-32.9
	Confidence Interval	(2-Sided) 95%; -103.1 to 37.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 33.8
	Estimation Comments	Adjusted mean difference was calculated as 'Randomised Nintedanib - randomised placebo'.

29. Secondary Outcome

Title	Participants Acceptability Based on the Size of Capsules at Week 24 - Patient Question
Description	Acceptability is defined as the overall ability and willingness of the participant to use the medicinal product as intended. Acceptability based on the capsule size was assessed by a acceptability questionnaire (1 item with 3 categories as shown below) for participants. In case the participant was considered not old enough as per investigator judgment the caregiver could assist with the completion. In addition to the commercially available 100 milligram (mg) soft capsules (oblong shape, 6 millimeter (mm) diameter and 16 mm length) and 150 mg soft capsules (oblong shape, 7 mm diameter and 18 mm length), 25 mg Nintedanib soft capsules of smaller size (oval shape, 5 mm diameter and 8 mm length) were provided in this trial for participants who were assigned to a dose smaller than 100 mg or were unable to swallow the larger 100 mg or 150 mg capsules.
Time Frame	Acceptability was assessed at Week 24

Outcome Measure Data

Analysis Population Description

Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with non-missing results were included in the analysis.

Arm/Group Title	DBP: Randomised to Placebo - Capsule Size of 25 mg Capsule	DBP: Randomised to Nintedanib - Capsule Size of 25 mg Capsule	DBP: Randomised to Placebo - Capsule Size of 100 mg Capsule	DBP: Randomised to Nintedanib - Capsule Size of 100 mg Capsule	DBP: Randomised to Placebo - Capsule Size of 150 mg Capsule	DBP: Randomised to Nintedanib - Capsule Size of 150 mg Capsule
Arm/Group Description:	This arm shows placebo randomised participants treated orally with placebo soft capsules of 25 milligram (mg) with a capsule size of 5 millimeter (mm) diameter and 8 mm length, oval shaped, twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Medication dosage per administration was 50 milligram (mg) [2 capsules with strength 25 mg], 75 mg [3 capsules with strength 25 mg], 100 mg [4 capsules with strength 25 mg] or 150 mg [6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). In this arm participants received placebo only (DBP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib soft capsules of 25 milligram (mg) with a capsule size of 5 millimeter (mm) diameter and 8 mm length, oval shaped, twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Medication dosage per administration was 50 milligram (mg) [2 capsules with strength 25 mg], 75 mg [3 capsules with strength 25 mg], 100 mg [4 capsules with strength 25 mg] or 150 mg [6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). In this arm participants received Nintedanib only (DBP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake.	This arm shows placebo randomised participants treated orally with placebo soft capsules of 100 mg with a capsule size of 6 mm diameter and 16 mm length, oblong shaped, twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Medication dosage per administration was 100 mg [1 capsules with strength 100 mg] based on the participant's weight at baseline (= 0 weeks). In this arm participants received placebo only (DBP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib soft capsules of 100 mg with a capsule size of 6 mm diameter and 16 mm length, oblong shaped, twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Medication dosage per administration was 100 mg [1 capsules with strength 100 mg] based on the participant's weight at baseline (= 0 weeks). In this arm participants received Nintedanib only (DBP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake.	This arm shows placebo randomised participants treated orally with placebo soft capsules of 150 mg with a capsule size of 7 mm diameter and 18 mm length, oblong shaped, twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Medication dosage per administration was 150 mg [1 capsules with strength 150 mg] based on the participant's weight at baseline (= 0 weeks). In this arm participants received placebo only (DBP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib soft capsules of 150 mg with a capsule size of 7 mm diameter and 18 mm length, oblong shaped, twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Medication dosage per administration was 150 mg [1 capsules with strength 150 mg] based on the participant's weight at baseline (= 0 weeks). In this arm participants received Nintedanib only (DBP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake.
Overall Number of Participants Analyzed	4	6	4	14	3	2
Measure Type: Count of Participants; Unit of Measure: Participants
OK	4 100.0%	6 100.0%	4 100.0%	14 100.0%	3 100.0%	2 100.0%
Large	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Very Large	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%

30. Secondary Outcome

Title	Participants Acceptability Based on the Size of Capsules at Week 24 - Investigator Question
Description	Acceptability is defined as the overall ability and willingness of the participant to use the medicinal product as intended. Acceptability based on the capsule size was assessed by a acceptability questionnaire (1 item with 3 categories as shown below) for investigators. In addition to the commercially available 100 milligram (mg) soft capsules (oblong shape, 6 millimeter (mm) diameter and 16 mm length) and 150 mg soft capsules (oblong shape, 7 mm diameter and 18 mm length), 25 mg Nintedanib soft capsules of smaller size (oval shape, 5 mm diameter and 8 mm length) were provided in this trial for participants who were assigned to a dose smaller than 100 mg or were unable to swallow the larger 100 mg or 150 mg capsules.
Time Frame	Acceptability was assessed at Week 24

Outcome Measure Data

Analysis Population Description

Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication.

Arm/Group Title	DBP: Randomised to Placebo - Capsule Size of 25 mg Capsule	DBP: Randomised to Nintedanib - Capsule Size of 25 mg Capsule	DBP: Randomised to Placebo - Capsule Size of 100 mg Capsule	DBP: Randomised to Nintedanib - Capsule Size of 100 mg Capsule	DBP: Randomised to Placebo - Capsule Size of 150 mg Capsule	DBP: Randomised to Nintedanib - Capsule Size of 150 mg Capsule
Arm/Group Description:	This arm shows placebo randomised participants treated orally with placebo soft capsules of 25 milligram (mg) with a capsule size of 5 millimeter (mm) diameter and 8 mm length, oval shaped, twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Medication dosage per administration was 50 milligram (mg) [2 capsules with strength 25 mg], 75 mg [3 capsules with strength 25 mg], 100 mg [4 capsules with strength 25 mg] or 150 mg [6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). In this arm participants received placebo only (DBP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib soft capsules of 25 milligram (mg) with a capsule size of 5 millimeter (mm) diameter and 8 mm length, oval shaped, twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Medication dosage per administration was 50 milligram (mg) [2 capsules with strength 25 mg], 75 mg [3 capsules with strength 25 mg], 100 mg [4 capsules with strength 25 mg] or 150 mg [6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). In this arm participants received Nintedanib only (DBP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake.	This arm shows placebo randomised participants treated orally with placebo soft capsules of 100 mg with a capsule size of 6 mm diameter and 16 mm length, oblong shaped, twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Medication dosage per administration was 100 mg [1 capsules with strength 100 mg] based on the participant's weight at baseline (= 0 weeks). In this arm participants received placebo only (DBP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib soft capsules of 100 mg with a capsule size of 6 mm diameter and 16 mm length, oblong shaped, twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Medication dosage per administration was 100 mg [1 capsules with strength 100 mg] based on the participant's weight at baseline (= 0 weeks). In this arm participants received Nintedanib only (DBP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake.	This arm shows placebo randomised participants treated orally with placebo soft capsules of 150 mg with a capsule size of 7 mm diameter and 18 mm length, oblong shaped, twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Medication dosage per administration was 150 mg [1 capsules with strength 150 mg] based on the participant's weight at baseline (= 0 weeks). In this arm participants received placebo only (DBP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib soft capsules of 150 mg with a capsule size of 7 mm diameter and 18 mm length, oblong shaped, twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Medication dosage per administration was 150 mg [1 capsules with strength 150 mg] based on the participant's weight at baseline (= 0 weeks). In this arm participants received Nintedanib only (DBP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake.
Overall Number of Participants Analyzed	4	6	4	14	3	2
Measure Type: Count of Participants; Unit of Measure: Participants
No	1 25.0%	2 33.3%	1 25.0%	2 14.3%	0 0.0%	1 50.0%
Yes	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Missing	3 75.0%	4 66.7%	3 75.0%	12 85.7%	3 100.0%	1 50.0%

31. Secondary Outcome

Title	Participants Acceptability Based on the Number of Capsules at Week 24 - Patient Question
Description	Acceptability is defined as the overall ability and willingness of the participant to use the medicinal product as intended. Acceptability based on the number of capsule was assessed by a acceptability questionnaire (1 item with 3 categories as shown below) for participants. In case the participant was considered not old enough as per investigator judgment the caregiver could assist with the completion. In addition to the commercially available 100 milligram (mg) soft capsules (oblong shape, 6 millimeter (mm) diameter and 16 mm length) and 150 mg soft capsules (oblong shape, 7 mm diameter and 18 mm length), 25 mg Nintedanib soft capsules of smaller size (oval shape, 5 mm diameter and 8 mm length) were provided in this trial for participants who were assigned to a dose smaller than 100 mg or were unable to swallow the larger 100 mg or 150 mg capsules. Medication dosage was based on the participant's body weight and number of capsules per administration ranged from 2 to >6 capsules.
Time Frame	Acceptability was assessed at Week 24

Outcome Measure Data

Analysis Population Description

Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with non-missing results were included in the analysis.

Arm/Group Title	DBP: Randomised to Placebo - 2 Capsules	DBP: Randomised to Nintedanib - 2 Capsules	DBP: Randomised to Placebo - 4 Capsules	DBP: Randomised to Nintedanib - 4 Capsules	DBP: Randomised to Placebo - 6 Capsules	DBP: Randomised to Nintedanib - 6 Capsules	DBP: Randomised to Placebo - >6 Capsules	DBP: Randomised to Nintedanib - >6 Capsules
Arm/Group Description:	This arm shows placebo randomised participants treated orally with 1 Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Medication dosage was per administration 100 mg [1 capsule with strength 100 mg] or 150 mg [1 capsule with strength 150 mg] based on the participant's weight at baseline (= 0 weeks). In this arm participants received placebo only (DBP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake.	This arm shows Nintedanib randomised participants treated orally with 1 Nintedanib soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Medication dosage was per administration 100 mg [1 capsule with strength 100 mg] or 150 mg [1 capsule with strength 150 mg] based on the participant's weight at baseline (= 0 weeks). In this arm participants received Nintedanib only (DBP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake.	This arm shows placebo randomised participants treated orally with 2 Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg], based on the participant's weight at baseline (= 0 weeks). In this arm participants received placebo only (DBP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake.	This arm shows Nintedanib randomised participants treated orally with 2 Nintedanib soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg], based on the participant's weight at baseline (= 0 weeks). In this arm participants received Nintedanib only (DBP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake.	This arm shows placebo randomised participants treated orally with 3 Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Medication dosage was per administration 75 mg [3 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo only (DBP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake.	This arm shows Nintedanib randomised participants treated orally with 3 Nintedanib soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Medication dosage was per administration 75 mg [3 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib only (DBP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake.	This arm shows placebo randomised participants treated orally with >3 Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Medication dosage was per administration 100 mg [4 capsules with strength 25 mg] or 150 mg [6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo only (DBP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake.	This arm shows Nintedanib randomised participants treated orally with >3 Nintedanib soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Medication dosage was per administration 100 mg [4 capsules with strength 25 mg] or 150 mg [6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). In this arm participants received Nintedanib only (DBP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake.
Overall Number of Participants Analyzed	7	16	2	3	1	3	1	0
Measure Type: Count of Participants; Unit of Measure: Participants
I had no problem swallowing them	7 100.0%	16 100.0%	2 100.0%	3 100.0%	1 100.0%	3 100.0%	1 100.0%	0
I swallowed them but it was difficult	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0
I could not swallow them sometimes	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0

32. Secondary Outcome

Title	Number of Participants With Occurrence of First Respiratory-related Hospitalization Over the Whole Trial
Description	Number of participants with occurrence of first respiratory-related hospitalization over the whole trial. The number of participants with first respiratory-related hospitalization is reported instead of a metric summarizing the time-to-event data with unit of time, as the numbers resulting from the Kaplan-Meier-analysis were even below the first quartile.
Time Frame	From first drug administration until the last drug intake + 28 days residual effect period (REP), up to 92.6 weeks

Outcome Measure Data

Analysis Population Description

Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication.

Arm/Group Title	DBP+OLNP: Randomised to Placebo	DBP+OLNP: Randomised to Nintedanib
Arm/Group Description:	This arm shows placebo randomised participants treated orally with a Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Participants who continued with the open-label Nintedanib period (OLNP) after the DBP switched to active Nintedanib treatment in the OLNP and were treated orally with Nintedanib twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo first (DBP) and then Nintedanib (OLNP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP and OLNP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib in both periods (DBP + OLNP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.
Overall Number of Participants Analyzed	13	26
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	3 11.5%

33. Secondary Outcome

Title	Number of Participants With Occurrence of First Acute Interstitial Lung Disease (ILD) Exacerbation or Death Over the Whole Trial
Description	Number of participants with occurrence of first acute Interstitial Lung Disease (ILD) exacerbation or death over the whole trial. The number of participants with first acute ILD exacerbation is reported instead of a metric summarizing the time-to-event data with unit of time, as the numbers resulting from the Kaplan-Meier-analysis were even below the first quartile.
Time Frame	From first drug administration until the last drug intake + 28 days REP, up to 92.6 weeks

Outcome Measure Data

Analysis Population Description

Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication.

Arm/Group Title	DBP+OLNP: Randomised to Placebo	DBP+OLNP: Randomised to Nintedanib
Arm/Group Description:	This arm shows placebo randomised participants treated orally with a Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Participants who continued with the open-label Nintedanib period (OLNP) after the DBP switched to active Nintedanib treatment in the OLNP and were treated orally with Nintedanib twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo first (DBP) and then Nintedanib (OLNP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP and OLNP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib in both periods (DBP + OLNP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.
Overall Number of Participants Analyzed	13	26
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	2 7.7%

34. Secondary Outcome

Title	Number of Participants With Occurrence of Death Over the Whole Trial
Description	Number of participants with occurrence of death over the whole trial over the whole trial was computed. The number of participants with occurrence of death is reported instead of a metric summarizing the time-to-event data with unit of time, as the numbers resulting from the Kaplan-Meier-analysis were even below the first quartile.
Time Frame	From first drug administration until the last drug intake + 28 days REP, up to 92.6 weeks

Outcome Measure Data

Analysis Population Description

Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication.

Arm/Group Title	DBP+OLNP: Randomised to Placebo	DBP+OLNP: Randomised to Nintedanib
Arm/Group Description:	This arm shows placebo randomised participants treated orally with a Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Participants who continued with the open-label Nintedanib period (OLNP) after the DBP switched to active Nintedanib treatment in the OLNP and were treated orally with Nintedanib twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo first (DBP) and then Nintedanib (OLNP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP and OLNP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib in both periods (DBP + OLNP). Participants in this arm do not entail participants from the 'randomised to placebo' arm. DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.
Overall Number of Participants Analyzed	13	26
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%

Adverse Events

Time Frame	Placebo-randomised DBP: From treatment start till end of DBP (defined as the day before first intake of open-label nintedanib (NIN) or last double-blind drug intake, up to 24.4 weeks + 28 days (REP), whichever is earlier) Placebo-randomised OLNP: From first intake of NIN till last intake of the OLNP, up to 64.6 weeks + 28 days (REP). Nintedanib-randomised DBP+OLNP: From first intake of NIN (DBP / OLNP) till last intake of NIN (DBP or OLNP), up to 85.1 weeks + 28 days (REP).
Adverse Event Reporting Description	Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication.
Arm/Group Title	DBP: Randomised to Placebo	OLNP: Randomised to Placebo and Switched to Nintedanib	DBP+OLNP: Randomised to Nintedanib (Nintedanib Exposure Period)
Arm/Group Description	This arm shows placebo randomised participants treated orally with a Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP). Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received placebo only (DBP). DBP: Planned was from first randomised trial drug intake to last blinded drug intake.	This arm shows participants who continued with the open-label Nintedanib period (OLNP) after the DBP, switched to active Nintedanib treatment in the OLNP and were treated orally with Nintedanib twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib only (OLNP). OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.	This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP and OLNP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib in both periods (DBP + OLNP). Participation in this arm do not entail participants from the 'randomised to placebo' arms. DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.
All-Cause Mortality
	DBP: Randomised to Placebo	OLNP: Randomised to Placebo and Switched to Nintedanib	DBP+OLNP: Randomised to Nintedanib (Nintedanib Exposure Period)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/13 (0.00%)	0/11 (0.00%)	0/26 (0.00%)
Serious Adverse Events
	DBP: Randomised to Placebo	OLNP: Randomised to Placebo and Switched to Nintedanib	DBP+OLNP: Randomised to Nintedanib (Nintedanib Exposure Period)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	1/13 (7.69%)	2/11 (18.18%)	5/26 (19.23%)
Gastrointestinal disorders
Tooth development disorder † 1	0/13 (0.00%)	0/11 (0.00%)	1/26 (3.85%)
Hepatobiliary disorders
Drug-induced liver injury † 1	0/13 (0.00%)	1/11 (9.09%)	0/26 (0.00%)
Liver injury † 1	0/13 (0.00%)	0/11 (0.00%)	1/26 (3.85%)
Infections and infestations
COVID-19 † 1	0/13 (0.00%)	0/11 (0.00%)	2/26 (7.69%)
Investigations
Carbon dioxide increased † 1	0/13 (0.00%)	0/11 (0.00%)	1/26 (3.85%)
Nervous system disorders
Frontal lobe epilepsy † 1	1/13 (7.69%)	0/11 (0.00%)	0/26 (0.00%)
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease † 1	0/13 (0.00%)	0/11 (0.00%)	1/26 (3.85%)
Respiratory distress † 1	0/13 (0.00%)	0/11 (0.00%)	1/26 (3.85%)
Vascular disorders
Neurogenic shock † 1	0/13 (0.00%)	1/11 (9.09%)	0/26 (0.00%)
1 Term from vocabulary, MedDRA 25.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	DBP: Randomised to Placebo	OLNP: Randomised to Placebo and Switched to Nintedanib	DBP+OLNP: Randomised to Nintedanib (Nintedanib Exposure Period)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	11/13 (84.62%)	11/11 (100.00%)	26/26 (100.00%)
Cardiac disorders
Right atrial hypertrophy † 1	0/13 (0.00%)	1/11 (9.09%)	0/26 (0.00%)
Congenital, familial and genetic disorders
Supernumerary teeth † 1	1/13 (7.69%)	0/11 (0.00%)	0/26 (0.00%)
Eye disorders
Eye pruritus † 1	1/13 (7.69%)	0/11 (0.00%)	0/26 (0.00%)
Lacrimation increased † 1	1/13 (7.69%)	0/11 (0.00%)	0/26 (0.00%)
Gastrointestinal disorders
Abdominal pain † 1	3/13 (23.08%)	4/11 (36.36%)	6/26 (23.08%)
Abdominal pain upper † 1	1/13 (7.69%)	0/11 (0.00%)	3/26 (11.54%)
Constipation † 1	1/13 (7.69%)	0/11 (0.00%)	2/26 (7.69%)
Dental caries † 1	3/13 (23.08%)	1/11 (9.09%)	7/26 (26.92%)
Dental cyst † 1	0/13 (0.00%)	0/11 (0.00%)	2/26 (7.69%)
Diarrhoea † 1	2/13 (15.38%)	6/11 (54.55%)	12/26 (46.15%)
Dyspepsia † 1	1/13 (7.69%)	1/11 (9.09%)	0/26 (0.00%)
Faeces soft † 1	2/13 (15.38%)	0/11 (0.00%)	1/26 (3.85%)
Gastrooesophageal reflux disease † 1	1/13 (7.69%)	0/11 (0.00%)	0/26 (0.00%)
Malpositioned teeth † 1	1/13 (7.69%)	0/11 (0.00%)	3/26 (11.54%)
Nausea † 1	3/13 (23.08%)	6/11 (54.55%)	6/26 (23.08%)
Paraesthesia oral † 1	0/13 (0.00%)	1/11 (9.09%)	0/26 (0.00%)
Rectal haemorrhage † 1	1/13 (7.69%)	0/11 (0.00%)	0/26 (0.00%)
Tooth deposit † 1	0/13 (0.00%)	1/11 (9.09%)	0/26 (0.00%)
Tooth development disorder † 1	1/13 (7.69%)	0/11 (0.00%)	6/26 (23.08%)
Tooth disorder † 1	1/13 (7.69%)	0/11 (0.00%)	0/26 (0.00%)
Tooth impacted † 1	2/13 (15.38%)	0/11 (0.00%)	2/26 (7.69%)
Vomiting † 1	3/13 (23.08%)	4/11 (36.36%)	7/26 (26.92%)
General disorders
Chest discomfort † 1	0/13 (0.00%)	1/11 (9.09%)	0/26 (0.00%)
Chest pain † 1	0/13 (0.00%)	2/11 (18.18%)	2/26 (7.69%)
Fatigue † 1	2/13 (15.38%)	0/11 (0.00%)	2/26 (7.69%)
Pain † 1	1/13 (7.69%)	0/11 (0.00%)	0/26 (0.00%)
Pyrexia † 1	1/13 (7.69%)	1/11 (9.09%)	4/26 (15.38%)
Immune system disorders
Multiple allergies † 1	0/13 (0.00%)	1/11 (9.09%)	0/26 (0.00%)
Seasonal allergy † 1	0/13 (0.00%)	1/11 (9.09%)	0/26 (0.00%)
Infections and infestations
COVID-19 † 1	1/13 (7.69%)	1/11 (9.09%)	7/26 (26.92%)
Gastrointestinal bacterial overgrowth † 1	0/13 (0.00%)	1/11 (9.09%)	0/26 (0.00%)
Influenza † 1	1/13 (7.69%)	0/11 (0.00%)	1/26 (3.85%)
Nasopharyngitis † 1	1/13 (7.69%)	2/11 (18.18%)	1/26 (3.85%)
Respiratory tract infection † 1	0/13 (0.00%)	0/11 (0.00%)	2/26 (7.69%)
Respiratory tract infection viral † 1	0/13 (0.00%)	1/11 (9.09%)	1/26 (3.85%)
Rhinitis † 1	0/13 (0.00%)	0/11 (0.00%)	4/26 (15.38%)
Sinusitis † 1	0/13 (0.00%)	1/11 (9.09%)	0/26 (0.00%)
Tooth abscess † 1	0/13 (0.00%)	0/11 (0.00%)	2/26 (7.69%)
Injury, poisoning and procedural complications
Burns second degree † 1	1/13 (7.69%)	0/11 (0.00%)	0/26 (0.00%)
Ligament sprain † 1	0/13 (0.00%)	1/11 (9.09%)	0/26 (0.00%)
Investigations
Blood thyroid stimulating hormone increased † 1	1/13 (7.69%)	0/11 (0.00%)	0/26 (0.00%)
Hepatic enzyme increased † 1	0/13 (0.00%)	0/11 (0.00%)	2/26 (7.69%)
SARS-CoV-2 test positive † 1	0/13 (0.00%)	2/11 (18.18%)	1/26 (3.85%)
Weight decreased † 1	0/13 (0.00%)	0/11 (0.00%)	2/26 (7.69%)
X-ray limb abnormal † 1	2/13 (15.38%)	0/11 (0.00%)	0/26 (0.00%)
Metabolism and nutrition disorders
Decreased appetite † 1	0/13 (0.00%)	1/11 (9.09%)	2/26 (7.69%)
Increased appetite † 1	1/13 (7.69%)	0/11 (0.00%)	0/26 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/13 (7.69%)	0/11 (0.00%)	2/26 (7.69%)
Pain in extremity † 1	1/13 (7.69%)	1/11 (9.09%)	1/26 (3.85%)
Nervous system disorders
Dizziness † 1	1/13 (7.69%)	0/11 (0.00%)	0/26 (0.00%)
Headache † 1	1/13 (7.69%)	2/11 (18.18%)	3/26 (11.54%)
Psychiatric disorders
Anxiety † 1	0/13 (0.00%)	1/11 (9.09%)	0/26 (0.00%)
Bruxism † 1	0/13 (0.00%)	1/11 (9.09%)	0/26 (0.00%)
Reproductive system and breast disorders
Menstruation delayed † 1	0/13 (0.00%)	0/11 (0.00%)	2/26 (7.69%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	1/13 (7.69%)	3/11 (27.27%)	0/26 (0.00%)
Dyspnoea exertional † 1	0/13 (0.00%)	1/11 (9.09%)	0/26 (0.00%)
Epistaxis † 1	2/13 (15.38%)	2/11 (18.18%)	0/26 (0.00%)
Nasal congestion † 1	0/13 (0.00%)	1/11 (9.09%)	0/26 (0.00%)
Oropharyngeal pain † 1	2/13 (15.38%)	2/11 (18.18%)	1/26 (3.85%)
Rhinorrhoea † 1	1/13 (7.69%)	0/11 (0.00%)	0/26 (0.00%)
Skin and subcutaneous tissue disorders
Hyperhidrosis † 1	1/13 (7.69%)	0/11 (0.00%)	0/26 (0.00%)
Melanosis † 1	1/13 (7.69%)	0/11 (0.00%)	0/26 (0.00%)
Vascular disorders
Flushing † 1	0/13 (0.00%)	1/11 (9.09%)	0/26 (0.00%)
1 Term from vocabulary, MedDRA 25.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

In the protocol it was planned to communicate the end of trial (EoT) once 30 participants had completed pharmacokinetic (PK) sampling at Week 26 or prematurely discontinued the trial and PK data was confirmed as adequate.

When the EoT was communicated, no participant had reached Week 100 yet, thus Week 100 time points were not assessable and the trial was completed as per protocol.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.

Results Point of Contact

• Name/Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim
• Phone: 1-800-243-0127
• EMail: clintriage.rdg@boehringer-ingelheim.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Deterding R, Griese M, Deutsch G, Warburton D, DeBoer EM, Cunningham S, Clement A, Schwerk N, Flaherty KR, Brown KK, Voss F, Schmid U, Schlenker-Herceg R, Verri D, Dumistracel M, Schiwek M, Stowasser S, Tetzlaff K, Clerisme-Beaty E, Young LR. Study design of a randomised, placebo-controlled trial of nintedanib in children and adolescents with fibrosing interstitial lung disease. ERJ Open Res. 2021 Jun 21;7(2):00805-2020. doi: 10.1183/23120541.00805-2020. eCollection 2021 Apr.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT04093024
• Other Study ID Numbers: 1199-0337; 2018-004530-14 ( EudraCT Number )
• First Submitted: September 16, 2019
• First Posted: September 17, 2019
• Results First Submitted: November 22, 2022
• Results First Posted: January 31, 2023
• Last Update Posted: April 25, 2023