Evaluation of Efficacy and Safety of Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) in Cystic Fibrosis Subjects Without an F508del Mutation

Phase 3

Completed

• Conditions: Cystic Fibrosis
• Interventions: Other: Placebo (matched to ELX/TEZ/IVA); Drug: ELX/TEZ/IVA; Other: Placebo (matched to IVA); Drug: IVA

• Registration Number: NCT05274269
• Lead Sponsor: Vertex Pharmaceuticals Incorporated

Brief Summary

This study evaluated the efficacy, pharmacodynamics (PD) and safety of ELX/TEZ/IVA in participants 6 years of age and older with a non-F508del ELX/TEZ/IVA-responsive cystic fibrosis transmembrane conductance regulator gene (CFTR) mutation.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-03-01
• Study First Submitted QC: 2022-03-01
• Study First Posted: 2022-03-10
• Study Start: 2022-05-09
• Primary Completion: 2023-07-05
• Study Completion: 2023-07-05
• Status Verified: 2024-07
• Results First Submitted: 2024-07-03
• Results First Submitted QC: 2024-07-31
• Last Update Submitted: 2024-07-31
• Results First Posted: 2024-08-01
• Last Update Posted: 2024-08-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 307

Inclusion Criteria

• Participant has a qualifying ELX/TEZ/IVA-responsive CFTR mutation and does not have an exclusionary CFTR mutation
• Forced expiratory volume in 1 second (FEV1) value >=40% and <=100% of predicted mean for age, sex, and height

Key

Exclusion Criteria

• History of solid organ or hematological transplantation
• Clinically significant cirrhosis with or without portal hypertension
• Lung infection with organisms associated with a more rapid decline in pulmonary status

Other protocol defined Inclusion/Exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo (matched to ELX/TEZ/IVA)	Participants received placebo matched to ELX/TEZ/IVA FDC in the morning and placebo matched to IVA in the evening for 24 weeks.
Placebo	Placebo (matched to IVA)	Participants received placebo matched to ELX/TEZ/IVA FDC in the morning and placebo matched to IVA in the evening for 24 weeks.
ELX/TEZ/IVA	ELX/TEZ/IVA	Participants 6 to less than (\<) 12 years of age and weighing \<30 kilogram (kg) at Day 1 received ELX 100 milligram (mg)/TEZ 50 mg /IVA 75 mg as fixed dose combination (FDC) tablets in the morning and IVA as mono tablet in the evening and those weighing more than or equal to (≥) 30 kg at Day 1 received ELX 200 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA as mono tablet in the evening for 24 weeks. Participants ≥12 years age at Day 1 received ELX 200 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA as mono tablet in the evening for 24 weeks.
ELX/TEZ/IVA	IVA	Participants 6 to less than (\<) 12 years of age and weighing \<30 kilogram (kg) at Day 1 received ELX 100 milligram (mg)/TEZ 50 mg /IVA 75 mg as fixed dose combination (FDC) tablets in the morning and IVA as mono tablet in the evening and those weighing more than or equal to (≥) 30 kg at Day 1 received ELX 200 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA as mono tablet in the evening for 24 weeks. Participants ≥12 years age at Day 1 received ELX 200 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA as mono tablet in the evening for 24 weeks.

Primary Outcome Measures

Name	Time	Method
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)	From Baseline Through Week 24	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

Secondary Outcome Measures

Name	Time	Method
Absolute Change in Sweat Chloride (SwCl)	From Baseline Through Week 24	Sweat samples were collected using an approved collection device.
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain (RD) Score	From Baseline Through Week 24	The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Number of Pulmonary Exacerbations (PEx)	From Baseline Through Week 24	Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Day 1 up to Week 28
Absolute Change in Body Mass Index (BMI)	From Baseline at Week 24	BMI was defined as weight in kilogram (kg) divided by height in square meter (m\^2).
Absolute Change in Weight	From Baseline at Week 24

Trial Locations

Locations (90)

Medizinische Universität Innsbruck; 🇦🇹 Innsbruck, Austria

Cliniques Universitaires de Bruxelles Hopital Erasme; 🇧🇪 Brussels, Belgium

Universitair Ziekenhuis Brussel - Campus Jette; 🇧🇪 Brussels, Belgium

Universitair Ziekenhuis Antwerpen (UZA) - Antwerp University Hospital; 🇧🇪 Edegem, Belgium

Universitair Ziekenhuis Gent; 🇧🇪 Gent, Belgium

Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg; 🇧🇪 Leuven, Belgium

Cliniques Universitaires Saint-Luc; 🇧🇪 Woluwe-Saint-Lambert, Belgium

Stollery Children's Hospital; 🇨🇦 Edmonton, Canada

Centre Hospitalier de l'Universite de Montreal (CHUM) Hotel-Dieu; 🇨🇦 Montreal, Canada

McGill University Health Centre, Glen Site, Montreal Children's Hospital; 🇨🇦 Montreal, Canada

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