A Study to Find Out Whether BI 1015550 Improves Lung Function in People With Progressive Fibrosing Interstitial Lung Diseases (PF-ILDs)

• ClinicalTrials.gov Identifier: NCT05321082
• Recruitment Status: Active, not recruiting
• First Posted: April 11, 2022
• Last Update Posted: April 30, 2024
• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

Tracking Information

• First Submitted Date: April 4, 2022
• First Posted Date: April 11, 2022
• Last Update Posted Date: April 30, 2024
• Actual Study Start Date: October 5, 2022
• Estimated Primary Completion Date: December 17, 2024 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: April 4, 2022): Absolute change from baseline in Forced Vital Capacity (FVC) (mL) at Week 52 [ Time Frame: at baseline, at week 52 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 19, 2022)

• Time to the first occurrence of any of the components of the composite endpoint: time to first acute ILD exacerbation, first hospitalization for respiratory cause, or death (whichever occurs first) over the duration of the trial [ Time Frame: up to 31 months ]
  Key secondary endpoint
• Time to first acute Interstitial Lung Disease (ILD) exacerbation or death over the duration of trial [ Time Frame: up to 31 months ]
• Time to hospitalization for respiratory cause or death over the duration of trial [ Time Frame: up to 31 months ]
• Time to absolute decline in Forced vital capacity (FVC) % predicted of >10% from baseline or death over the duration of the trial [ Time Frame: up to 31 months ]
• Time to absolute decline in Diffusing Capacity (of Lung) for Carbon Monoxide (DLCO) % predicted of >15% from baseline or death over the duration of the trial [ Time Frame: up to 31 months ]
• Time to death over the duration of trial [ Time Frame: up to 31 months ]
• Absolute change from baseline in Living with Pulmonary Fibrosis (L-PF) Symptoms Dyspnea domain score at Week 52 [ Time Frame: at baseline, at week 52 ]
  The L-PF is a 49-item questionnaire with two modules: Symptoms (28 items) and Impact (21 items). The Symptom score has three domain scores: dyspnea, cough, and fatigue, as well as a total symptom score. Items have response options on a five-option numeric rating score with an anchor of 0 "Not at all" to 4 "Extremely", with higher numbers indicating a greater impairment.
• Absolute change from baseline in Living with Pulmonary Fibrosis (L-PF) Symptoms Cough domain score at Week 52 [ Time Frame: at baseline, at week 52 ]
  The L-PF is a 44-item questionnaire divided into two modules: Symptoms (23 items) and Impacts (21 items). The Symptoms module assesses shortness of breath, cough and fatigue in the past 24 hours. Items have response options on a five-option numeric rating score with an anchor of 0 "Not at all" to 4 "Extremely", with higher numbers indicating a greater impairment.
• Absolute change from baseline in Living with Pulmonary Fibrosis (L-PF) Symptoms Fatigue domain score at Week 52 [ Time Frame: at baseline, at week 52 ]
  The L-PF is a 44-item questionnaire divided into two modules: Symptoms (23 items) and Impacts (21 items). The Symptoms module assesses shortness of breath, cough and fatigue in the past 24 hours. Items have response options on a five-option numeric rating score with an anchor of 0 "Not at all" to 4 "Extremely", with higher numbers indicating a greater impairment.
• Absolute change from baseline in FVC % predicted at Week 52 [ Time Frame: at baseline, at week 52 ]
• Absolute change from baseline in DLCO % predicted at Week 52 [ Time Frame: at baseline, at week 52 ]

Original Secondary Outcome Measures (submitted: April 4, 2022)

• Key secondary endpoint: Absolute change from baseline in Living with Pulmonary Fibrosis (L-PF) Symptoms dyspnea domain score at Week 52 [ Time Frame: at baseline, at week 52 ]
  The L-PF is a 49-item questionnaire with two modules: Symptoms (28 items) and Impact (21 items). The Symptom score has three domain scores: dyspnea, cough, and fatigue, as well as a total symptom score. Items have response options on a five-option numeric rating score with an anchor of 0 "Not at all" to 4 "Extremely", with higher numbers indicating a greater impairment.
• Key secondary endpoint: Absolute change from baseline in Living with Pulmonary Fibrosis (L-PF) Symptoms cough domain score at Week 52 [ Time Frame: at baseline, at week 52 ]
  The L-PF is a 44-item questionnaire divided into two modules: Symptoms (23 items) and Impacts (21 items). The Symptoms module assesses shortness of breath, cough and fatigue in the past 24 hours. Items have response options on a five-option numeric rating score with an anchor of 0 "Not at all" to 4 "Extremely", with higher numbers indicating a greater impairment.
• Time to first acute Interstitial Lung Disease (ILD) exacerbation or death over the whole trial [ Time Frame: up to 32 months ]
• Time to hospitalization for respiratory cause or death over the whole trial [ Time Frame: up to 32 months ]
• Time to 10% absolute FVC drop from baseline or death over the whole trial [ Time Frame: up to 32 months ]
• Time to death over the whole trial [ Time Frame: up to 32 months ]
• Time to first acute ILD exacerbation over the whole trial [ Time Frame: up to 32 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Find Out Whether BI 1015550 Improves Lung Function in People With Progressive Fibrosing Interstitial Lung Diseases (PF-ILDs)
• Official Title: A Double Blind, Randomized, Placebo-controlled Trial Evaluating the Efficacy and Safety of BI 1015550 Over at Least 52 Weeks in Patients With Progressive Fibrosing Interstitial Lung Diseases (PF-ILDs)

Brief Summary

This study is open to adults with Progressive Fibrosing Interstitial Lung Diseases (PF-ILDs). People who have a form of PF-ILD other than Idiopathic Pulmonary Fibrosis (IPF) can join the study. If they already take nintedanib, they can continue treatment throughout the study.

The purpose of this study is to find out whether a medicine called BI 1015550 helps people with PF-ILD. Participants are put into 3 groups randomly, which means by chance. Participants in 2 groups take different doses of BI 1015550 as tablets twice a day. Participants in the placebo group take placebo tablets twice a day. Placebo tablets look like BI 1015550 tablets but do not contain any medicine.

Participants are in the study for up to two and a half years. During the first year, they visit the study site 10 times. Afterwards, they visit the study site every 3 months. The doctors regularly test participants' lung function. The results of the lung function tests are compared between the groups. The doctors also regularly check participants' health and take note of any unwanted effects.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Lung Diseases, Interstitial

Intervention

• Drug: BI 1015550
  BI 1015550
  Other Name: Nerandomilast
• Drug: Placebo
  Placebo

Study Arms

• Experimental: BI 1015550 low dose
  Intervention: Drug: BI 1015550
• Experimental: BI 1015550 high dose
  Intervention: Drug: BI 1015550
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 10, 2024): 1178
• Original Estimated Enrollment (submitted: April 4, 2022): 694
• Estimated Study Completion Date: March 19, 2025
• Estimated Primary Completion Date: December 17, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion criteria

1. Patients ≥18 years old at the time of signed informed consent.
2. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.
3. Diagnosis of progressive fibrosing ILD other than IPF (physician confirmed).

4. Patients may be either:

   • on a stable therapy* with nintedanib for at least 12 weeks prior to Visit 1 and during screening and are planning to stay on this background treatment after randomization. (*stable therapy is defined as a tolerated regimen of nintedanib (with no dose changes) for at least 12 weeks)
   • not on treatment with nintedanib for at least 8 weeks prior to Visit 1 and during the screening period (e.g. either Antifibrotic (AF)-treatment naïve or previously discontinued) and do not plan to start or re-start antifibrotic treatment.
5. Forced Vital Capacity (FVC) ≥45% of predicted normal at Visit 1.
6. DLCO ≥25% of predicted normal corrected for hemoglobin (Hb) at Visit 1.
7. Women of childbearing potential (WOCBP) must be ready and able to use highly effective methods of birth control. WOCBP taking oral contraceptives (OCs) also have to use one barrier method
8. Patients treated with permitted immunosuppressive agents (other than corticosteroids) for an underlying systemic disease (e.g. Methotrexate (MTX), Azathioprine (AZA)) need to be on a stable treatment for at least 12 weeks prior to Visit 1 and during the screening period.

Exclusion criteria

1. Prebronchodilator Forced Expiratory Volume in 1 second (FEV1)/Forced vital capacity (FVC) <0.7 at Visit 1
2. In the opinion of the Investigator, other clinically significant pulmonary abnormalities.
3. Acute Interstitial Lung Disease (ILD) exacerbation within 3 months prior to Visit 1 and/or during the screening period (investigator-determined).
4. Relevant chronic or acute infections including human immunodeficiency virus (HIV) and viral hepatitis.
5. Patients having developed ILD due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection/coronavirus disease 2019 (COVID-19) within 12 months of screening (based on investigators judgement).
6. Major surgery (major according to the investigator's assessment) performed within 6 weeks prior to Visit 2 or planned during the trial period, e.g. hip replacement. Registration on lung transplantation list would not be considered as planned major surgery.
7. Any documented active or suspected malignancy or history of malignancy within 5 years prior to Visit 1, except appropriately treated basal cell carcinoma of the skin, in situ squamous cell carcinoma of the skin or in situ carcinoma of uterine cervix.
8. Aspartate aminotransferase (AST) or Alanine Aminotransferase (ALT) >2.5 x upper limit of normal (ULN) or total Bilirubin >1.5 x ULN at Visit 1.

Further exclusion criteria apply.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Croatia, Czechia, Denmark, Estonia, Finland, France, Georgia, Germany, Greece, Hungary, India, Ireland, Israel, Italy, Japan, Korea, Republic of, Malaysia, Mexico, Netherlands, New Zealand, Norway, Poland, Portugal, Puerto Rico, Saudi Arabia, Serbia, Singapore, Slovenia, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT05321082
• Other Study ID Numbers: 1305-0023; 2022-001134-11 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

Once the criteria in section "Time Frame" are fulfilled, researchers can use the following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement".

Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.

• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: After structured results have been posted, all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.
• URL: https://www.mystudywindow.com/msw/datasharing

• Current Responsible Party: Boehringer Ingelheim
• Original Responsible Party: Same as current
• Current Study Sponsor: Boehringer Ingelheim
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Boehringer Ingelheim
• Verification Date: April 2024