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Evaluation of ELX/TEZ/IVA in Cystic Fibrosis (CF) Subjects 2 Through 5 Years

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04537793
Recruitment Status : Completed
First Posted : September 3, 2020
Results First Posted : June 28, 2023
Last Update Posted : June 28, 2023
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Sequential Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Cystic Fibrosis
Interventions Drug: ELX/TEZ/IVA
Drug: IVA
Enrollment 83
Recruitment Details The study was conducted in 2 parts, Part A and Part B. The Participant flow was planned to be presented for the overall treatment arms (i.e. Part A and Part B), irrespective of weight-based dose regimen.
Pre-assignment Details This study was conducted in participants with cystic fibrosis (CF) aged 2 through 5 years of age (inclusive).
Arm/Group Title Part A: ELX/TEZ/IVA Part B: ELX/TEZ/IVA
Hide Arm/Group Description Participants weighing greater than or equals to (>=)14 kg at screening received elexacaftor (ELX) 100 milligrams (mg) once daily (qd)/tezacaftor (TEZ) 50 mg qd/ivacaftor (IVA) 75 mg every 12 hours (q12h) in the treatment period for 15 days. Participants weighing >=14 kg at screening received ELX 100mg qd/TEZ 50mg qd/IVA 75 mg q12h and participants weighing >=10 kg to less than (<)14 kg received ELX 80mg qd/TEZ 40mg qd/IVA 60 mg once every morning (qAM) and IVA 59.5 mg once every evening (qPM) in the treatment period for 24 weeks.
Period Title: Part A (15 Days)
Started 18 0
Completed 18 0
Not Completed 0 0
Period Title: Part B (24 Weeks)
Started 0 75 [1]
Completed 0 74
Not Completed 0 1
Reason Not Completed
Adverse Event             0             1
[1]
Out of the 18 participants from Part A, 10 participants also participated in Part B of the study.
Arm/Group Title ELX/TEZ/IVA
Hide Arm/Group Description

Part A: Participants weighing greater than or equal to (>=)14 kilograms (kg) at screening received ELX 100 milligrams (mg) once daily (qd)/TEZ 50 mg qd/IVA 75 mg every 12 hours (q12h) in the treatment period for 15 days.

Part B: Participants weighing >=14 kg at screening received ELX 100mg qd/TEZ 50mg qd/IVA 75 mg q12h and participants weighing >=10 kg to less than (<)14 kg received ELX 80mg qd/TEZ 40mg qd/IVA 60 mg once every morning (qAM) and IVA 59.5 mg once every evening (qPM) in the treatment period for 24 weeks.
Overall Number of Baseline Participants 83
Hide Baseline Analysis Population Description
All participants who received at least one dose of the study drug during the treatment period were included in the baseline analysis.
Age, Categorical   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Part A Number Analyzed 18 participants
<=18 years
18
 100.0%
Between 18 and 65 years
0
   0.0%
>=65 years
0
   0.0%
Part B Number Analyzed 75 participants
<=18 years
75
 100.0%
Between 18 and 65 years
0
   0.0%
>=65 years
0
   0.0%
[1]
Measure Analysis Population Description: The Baseline data were planned to be presented for the overall treatment arms (i.e. Part A and Part B), irrespective of weight-based dose regimen. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Part A Number Analyzed 18 participants
Female
11
  61.1%
Male
7
  38.9%
Part B Number Analyzed 75 participants
Female
41
  54.7%
Male
34
  45.3%
[1]
Measure Analysis Population Description: The Baseline data were planned to be presented for the overall treatment arms (i.e. Part A and Part B), irrespective of weight-based dose regimen. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race/Ethnicity, Customized   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Part A Number Analyzed 18 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
18
 100.0%
Not collected per local regulations
0
   0.0%
Part B Number Analyzed 75 participants
Hispanic or Latino
6
   8.0%
Not Hispanic or Latino
63
  84.0%
Not collected per local regulations
6
   8.0%
[1]
Measure Analysis Population Description: The Baseline data were planned to be presented for the overall treatment arms (i.e. Part A and Part B), irrespective of weight-based dose regimen. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race/Ethnicity, Customized   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Part A Number Analyzed 18 participants
White
18
 100.0%
Black or African American
0
   0.0%
Not collected per local regulations
0
   0.0%
Part B Number Analyzed 75 participants
White
68
  90.7%
Black or African American
1
   1.3%
Not collected per local regulations
6
   8.0%
[1]
Measure Analysis Population Description: The Baseline data were planned to be presented for the overall treatment arms (i.e. Part A and Part B), irrespective of weight-based dose regimen. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
1.Primary Outcome
Title Part A: Observed Pre-dose Concentration (Ctrough) of ELX,TEZ,IVA, and Relevant Metabolites
Hide Description [Not Specified]
Time Frame From Day 1 through Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set included participants who received at least 1 dose of study drug. Here the "Number Analyzed" signifies those participants who were evaluable at specified time point.
Arm/Group Title Part A: ELX/TEZ/IVA
Hide Arm/Group Description:
Participants weighing >=14 kg at screening received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h in the treatment period for 15 days.
Overall Number of Participants Analyzed 18
Mean (Standard Deviation)
Unit of Measure: micrograms per milliliter (mcg/ml)
Day 1: ELX Number Analyzed 18 participants
0.00  (0.00)
Day 8: ELX Number Analyzed 18 participants
3.44  (2.09)
Day 15: ELX Number Analyzed 17 participants
3.69  (2.11)
Day 1: ELX-M23 Number Analyzed 18 participants
0.00  (0.00)
Day 8: ELX-M23 Number Analyzed 18 participants
2.39  (1.65)
Day 15: ELX-M23 Number Analyzed 17 participants
2.47  (1.65)
Day 1: TEZ Number Analyzed 18 participants
0.00  (0.00)
Day 8: TEZ Number Analyzed 18 participants
1.86  (1.07)
Day 15: TEZ Number Analyzed 17 participants
1.85  (1.10)
Day 1: TEZ-M1 Number Analyzed 18 participants
0.00  (0.00)
Day 8: TEZ-M1 Number Analyzed 18 participants
6.42  (1.42)
Day 15: TEZ-M1 Number Analyzed 17 participants
7.68  (1.52)
Day 1: IVA Number Analyzed 18 participants
0.00  (0.00)
Day 8: IVA Number Analyzed 18 participants
0.702  (0.503)
Day 15: IVA Number Analyzed 17 participants
0.746  (0.526)
Day 1: IVA-M1 Number Analyzed 18 participants
0.00  (0.00)
Day 8: IVA-M1 Number Analyzed 18 participants
1.78  (0.990)
Day 15: IVA-M1 Number Analyzed 17 participants
1.91  (0.990)
2.Primary Outcome
Title Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment- Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Hide Description [Not Specified]
Time Frame From Day 1 up to Day 43
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set for Part A included all participants who received at least 1 dose of study drug in Part A. This outcome measure was planned only for Part A arm.
Arm/Group Title Part A: ELX/TEZ/IVA
Hide Arm/Group Description:
Participants weighing >=14 kg at screening received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h in the treatment period for 15 days.
Overall Number of Participants Analyzed 18
Measure Type: Number
Unit of Measure: participants
Participants with TEAEs 15
Participants with SAEs 0
3.Primary Outcome
Title Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Hide Description [Not Specified]
Time Frame From Day 1 up to Week 28
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set for Part B included all participants who received at least 1 dose of study drug in Part B. The safety and tolerability analysis for Part B was assessed for the overall treatment arm, irrespective of weight-based dose regimen. Therefore, the analysis is reported for the single triple combination (Part B: ELX/TEZ/IVA) arm.
Arm/Group Title Part B: ELX/TEZ/IVA
Hide Arm/Group Description:
Participants weighing >=14 kg at screening received ELX 100mg qd/TEZ 50mg qd/IVA 75 mg q12h and participants weighing >=10 kg to <14 kg received ELX 80mg qd/TEZ 40mg qd/IVA 60 mg qAM and IVA 59.5 mg qPM in the treatment period for 24 weeks.
Overall Number of Participants Analyzed 75
Measure Type: Number
Unit of Measure: participants
Participants with TEAEs 74
Participants with SAEs 2
4.Secondary Outcome
Title Part B: Observed Pre-dose Plasma Concentration (Ctrough) of ELX,TEZ,IVA and Relevant Metabolites
Hide Description [Not Specified]
Time Frame From Day 1 through Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
PK set included participants who received at least 1 dose of study drug. Here the "Number Analyzed" signifies those participants who were evaluable at specified time point.
Arm/Group Title Part B: ELX/TEZ/IVA (≥10 kg to <14 kg) Part B: ELX/TEZ/IVA (≥14 kg)
Hide Arm/Group Description:
Participants weighing >=10 kg to l <14 kg received ELX80mg qd/TEZ 40mg qd/IVA 60 mg qAM and IVA 59.5 qPM in the treatment period for 24 weeks.
Participants weighing >=14 kg at screening received ELX100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h in the treatment period for 24 weeks.
Overall Number of Participants Analyzed 16 59
Mean (Standard Deviation)
Unit of Measure: micrograms per milliliter (mcg/ml)
Day 15: ELX Number Analyzed 14 participants 54 participants
2.91  (1.38) 3.87  (2.75)
Week 4: ELX Number Analyzed 16 participants 59 participants
3.13  (1.90) 3.56  (2.19)
Week 12: ELX Number Analyzed 16 participants 56 participants
2.48  (1.65) 3.49  (2.22)
Week 16: ELX Number Analyzed 15 participants 58 participants
3.01  (1.11) 3.18  (2.19)
Day 15: ELX-M23 Number Analyzed 14 participants 54 participants
1.85  (1.12) 2.33  (1.87)
Week 4: ELX-M23 Number Analyzed 16 participants 59 participants
2.32  (2.01) 2.22  (1.66)
Week 12: ELX-M23 Number Analyzed 16 participants 56 participants
1.48  (1.27) 2.17  (1.69)
Week 16: ELX-M23 Number Analyzed 15 participants 58 participants
1.73  (0.828) 1.94  (1.58)
Day 15: TEZ Number Analyzed 14 participants 52 participants
1.73  (0.666) 2.14  (1.72)
Week 4: TEZ Number Analyzed 16 participants 59 participants
1.62  (0.716) 1.79  (0.947)
Week 12: TEZ Number Analyzed 16 participants 56 participants
1.60  (0.951) 1.76  (1.10)
Week 16: TEZ Number Analyzed 15 participants 58 participants
1.52  (0.701) 1.80  (1.42)
Day 15: TEZ-M1 Number Analyzed 14 participants 52 participants
7.07  (1.08) 7.07  (2.11)
Week 4: TEZ-M1 Number Analyzed 16 participants 59 participants
6.80  (1.64) 7.09  (2.18)
Week 12: TEZ-M1 Number Analyzed 16 participants 56 participants
7.06  (2.37) 7.18  (2.38)
Week 16: TEZ-M1 Number Analyzed 15 participants 58 participants
6.88  (1.94) 6.95  (2.77)
Day 15: IVA Number Analyzed 14 participants 52 participants
0.549  (0.373) 0.661  (0.552)
Week 4: IVA Number Analyzed 16 participants 59 participants
0.535  (0.402) 0.594  (0.405)
Week 12: IVA Number Analyzed 16 participants 56 participants
0.383  (0.203) 0.530  (0.474)
Week 16: IVA Number Analyzed 15 participants 58 participants
0.483  (0.347) 0.580  (0.511)
Day 15: IVA-M1 Number Analyzed 14 participants 52 participants
1.47  (0.969) 1.67  (0.961)
Week 4: IVA-M1 Number Analyzed 16 participants 59 participants
1.64  (1.29) 1.52  (0.737)
Week 12: IVA-M1 Number Analyzed 16 participants 56 participants
1.19  (0.602) 1.45  (0.907)
Week 16: IVA-M1 Number Analyzed 15 participants 58 participants
1.24  (0.673) 1.51  (0.911)
5.Secondary Outcome
Title Part B: Absolute Change in Sweat Chloride (SwCl)
Hide Description Sweat samples were collected using an approved collection device.
Time Frame From Baseline through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (Part B). The efficacy analysis for Part B was assessed for the overall treatment arm, irrespective of weight-based dose regimen. Therefore, the analysis is reported for the single triple combination (Part B: ELX/TEZ/IVA) arm.
Arm/Group Title Part B: ELX/TEZ/IVA
Hide Arm/Group Description:
Participants weighing >=14 kg received ELX 100mg qd/TEZ 50mg qd/IVA 75 mg q12h and participants weighing >=10 kg to <14 kg received ELX 80mg qd/TEZ 40mg qd/IVA 60 mg qAM and IVA 59.5mg qPM in the treatment period for 24 weeks.
Overall Number of Participants Analyzed 75
Least Squares Mean (95% Confidence Interval)
Unit of Measure: millimole per liter (mmol/L)
-57.9
(-61.3 to -54.6)
6.Secondary Outcome
Title Part B: Absolute Change in Lung Clearance Index 2.5 (LCI 2.5)
Hide Description The LCI2.5 index is the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting values and is calculated by dividing the sum of exhaled tidal breaths (cumulative exhaled volume (CEV)) by simultaneously measured functional residual capacity (FRC). An LCI of 7.5 and below is normal; values greater than 7.5 are abnormal. LCI is able to detect abnormalities in lung function earlier than more traditional modalities such as spirometry.
Time Frame From Baseline through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (Part B). The efficacy analysis for Part B was assessed for the overall treatment arm, irrespective of weight-based dose regimen. Therefore, the analysis is reported for the single triple combination (Part B: ELX/TEZ/IVA) arm.
Arm/Group Title Part B: ELX/TEZ/IVA
Hide Arm/Group Description:
Participants weighing >=14 kg received ELX 100 mg qd/TEZ 50mg qd/IVA 75 mg q12h and participants weighing >=10 kg to less than <14 kg received ELX 80 mg qd/TEZ 40mg qd/IVA 60 mg qAM and IVA 59.5 mg qPM in the treatment period for 24 weeks.
Overall Number of Participants Analyzed 63
Least Squares Mean (95% Confidence Interval)
Unit of Measure: index
-0.83
(-1.01 to -0.66)
Time Frame Day 1 Through Safety Follow-up Visit (up to Day 43 for Part A, up to Week 28 for Part B)
Adverse Event Reporting Description

The safety analysis for Part B was assessed for the overall treatment arm, irrespective of weight-based dose regimen.Therefore, the analysis is reported for the single triple combination (Part B: ELX/TEZ/IVA) arm.

MedDRA version 23.1 applied for Part A, MedDRA version 25.0 applied for Part B.
 
Arm/Group Title Part A: ELX/TEZ/IVA Part B: ELX/TEZ/IVA
Hide Arm/Group Description Participants weighing >=14 kg at screening received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h in the treatment period for 15 days. Participants weighing >=14 kg at screening received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h and participants weighing >=10 kg to <14 kg received ELX 80 mg qd/TEZ 40 mg qd/IVA 60 mg qAM and IVA 59.5 mg qPM in the treatment period for 24 weeks.
All-Cause Mortality
Part A: ELX/TEZ/IVA Part B: ELX/TEZ/IVA
Affected / at Risk (%) Affected / at Risk (%)
Total   0/18 (0.00%)   0/75 (0.00%) 
Hide Serious Adverse Events
Part A: ELX/TEZ/IVA Part B: ELX/TEZ/IVA
Affected / at Risk (%) Affected / at Risk (%)
Total   0/18 (0.00%)   2/75 (2.67%) 
Gastrointestinal disorders     
Anal incontinence † 1  0/18 (0.00%)  1/75 (1.33%) 
Infections and infestations     
Infective pulmonary exacerbation of cystic fibrosis † 1  0/18 (0.00%)  1/75 (1.33%) 
Psychiatric disorders     
Abnormal behaviour † 1  0/18 (0.00%)  1/75 (1.33%) 
Renal and urinary disorders     
Urinary incontinence † 1  0/18 (0.00%)  1/75 (1.33%) 
1
Term from vocabulary, MedDRA 23.1,25.0
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Part A: ELX/TEZ/IVA Part B: ELX/TEZ/IVA
Affected / at Risk (%) Affected / at Risk (%)
Total   15/18 (83.33%)   71/75 (94.67%) 
Gastrointestinal disorders     
Abdominal discomfort † 1  0/18 (0.00%)  5/75 (6.67%) 
Abdominal pain † 1  1/18 (5.56%)  4/75 (5.33%) 
Constipation † 1  1/18 (5.56%)  6/75 (8.00%) 
Diarrhoea † 1  0/18 (0.00%)  5/75 (6.67%) 
Vomiting † 1  0/18 (0.00%)  21/75 (28.00%) 
General disorders     
Pyrexia † 1  1/18 (5.56%)  26/75 (34.67%) 
Infections and infestations     
COVID-19 † 1  0/18 (0.00%)  14/75 (18.67%) 
Infective pulmonary exacerbation of cystic fibrosis † 1  0/18 (0.00%)  8/75 (10.67%) 
Nasopharyngitis † 1  0/18 (0.00%)  6/75 (8.00%) 
Upper respiratory tract infection † 1  1/18 (5.56%)  11/75 (14.67%) 
Injury, poisoning and procedural complications     
Scratch † 1  1/18 (5.56%)  0/75 (0.00%) 
Skin abrasion † 1  1/18 (5.56%)  0/75 (0.00%) 
Investigations     
Alanine aminotransferase increased † 1  3/18 (16.67%)  8/75 (10.67%) 
Aspartate aminotransferase increased † 1  2/18 (11.11%)  4/75 (5.33%) 
Gamma-glutamyltransferase increased † 1  1/18 (5.56%)  4/75 (5.33%) 
SARS-CoV-2 test positive † 1  0/18 (0.00%)  7/75 (9.33%) 
Metabolism and nutrition disorders     
Decreased appetite † 1  0/18 (0.00%)  9/75 (12.00%) 
Hyperamylasaemia † 1  1/18 (5.56%)  0/75 (0.00%) 
Hyperlipasaemia † 1  1/18 (5.56%)  0/75 (0.00%) 
Nervous system disorders     
Headache † 1  0/18 (0.00%)  7/75 (9.33%) 
Product Issues     
Product taste abnormal † 1  1/18 (5.56%)  0/75 (0.00%) 
Psychiatric disorders     
Irritability † 1  0/18 (0.00%)  4/75 (5.33%) 
Respiratory, thoracic and mediastinal disorders     
Cough † 1  4/18 (22.22%)  46/75 (61.33%) 
Nasal congestion † 1  0/18 (0.00%)  13/75 (17.33%) 
Productive cough † 1  1/18 (5.56%)  3/75 (4.00%) 
Rhinorrhoea † 1  3/18 (16.67%)  25/75 (33.33%) 
Sputum increased † 1  1/18 (5.56%)  0/75 (0.00%) 
Skin and subcutaneous tissue disorders     
Papule † 1  1/18 (5.56%)  0/75 (0.00%) 
Pruritus † 1  1/18 (5.56%)  1/75 (1.33%) 
Rash † 1  2/18 (11.11%)  12/75 (16.00%) 
Rash erythematous † 1  1/18 (5.56%)  1/75 (1.33%) 
Urticaria † 1  1/18 (5.56%)  1/75 (1.33%) 
1
Term from vocabulary, MedDRA 23.1,25.0
†
Indicates events were collected by systematic assessment
[Not Specified]
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Monitor
Organization: Vertex Pharmaceuticals Incorporated
Phone: 617-341-6777
EMail: medicalinfo@vrtx.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT04537793    
Other Study ID Numbers: VX20-445-111
2020-002251-38 ( EudraCT Number )
First Submitted: August 28, 2020
First Posted: September 3, 2020
Results First Submitted: June 2, 2023
Results First Posted: June 28, 2023
Last Update Posted: June 28, 2023