A Phase 3 Study of VX-445 Combination Therapy in Cystic Fibrosis (CF) Subjects Heterozygous for F508del and a Gating or Residual Function Mutation (F/G and F/RF Genotypes)

Phase 3

Completed

• Conditions: Cystic Fibrosis
• Interventions: Drug: IVA; Drug: ELX/TEZ/IVA; Drug: TEZ/IVA

• Registration Number: NCT04058353
• Lead Sponsor: Vertex Pharmaceuticals Incorporated

Brief Summary

This study will evaluate the efficacy, safety and pharmacodynamics of elexacaftor (ELX, VX-445) in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are heterozygous for F508del and a gating or residual function mutation (F/G and F/RF genotypes).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-08-14
• Study First Submitted QC: 2019-08-14
• Study First Posted: 2019-08-15
• Study Start: 2019-08-28
• Primary Completion: 2020-06-12
• Study Completion: 2020-06-12
• Status Verified: 2021-06
• Results First Submitted: 2021-06-11
• Results First Submitted QC: 2021-06-11
• Last Update Submitted: 2021-06-11
• Results First Posted: 2021-07-02
• Last Update Posted: 2021-07-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 271

Inclusion Criteria

• Subject has a confirmed diagnosis of CF and is heterozygous for F508del and either a gating or residual function mutation (F/G and F/RF genotypes)
• Forced expiratory volume in 1 second (FEV1) value ≥40% and ≤90% of predicted mean for age, sex, and height

Key

Exclusion Criteria

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

Other protocol defined Inclusion/Exclusion criteria may apply

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control: IVA or TEZ/IVA	IVA	Following an IVA or TEZ/IVA run-in period of 4 weeks, participants either received IVA 150 milligrams (mg) every 12 hours (q12h) or TEZ 100 mg once daily (qd)/IVA 150 mg q12h in the treatment period for 8 weeks.
Control: IVA or TEZ/IVA	TEZ/IVA	Following an IVA or TEZ/IVA run-in period of 4 weeks, participants either received IVA 150 milligrams (mg) every 12 hours (q12h) or TEZ 100 mg once daily (qd)/IVA 150 mg q12h in the treatment period for 8 weeks.
TC: ELX/TEZ/IVA	ELX/TEZ/IVA	Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks.
TC: ELX/TEZ/IVA	IVA	Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks.

Primary Outcome Measures

Name	Time	Method
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for ELX/TEZ/IVA Group	From Baseline Through Week 8	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 ppFEV1 for the ELX/TEZ/IVA Group Compared to the Control Group	From Baseline Through Week 8	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Absolute Change in Sweat Chloride (SwCl) for ELX/TEZ/IVA Group	From Baseline Through Week 8	Sweat samples were collected using an approved collection device.
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for ELX/TEZ/IVA Group	From Baseline Through Week 8	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.
Absolute Change in CFQ-R Respiratory Domain Score for ELX/TEZ/IVA Group Compared to the Control Group	From Baseline Through Week 8	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.
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	Day 1 up to Week 12
Absolute Change in SwCl for ELX/TEZ/IVA Group Compared to the Control Group	From Baseline Through Week 8	Sweat samples were collected using an approved collection device.

Trial Locations

Locations (93)

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Banner University of Arizona Medical Center; 🇺🇸 Tucson, Arizona, United States

Miller Children's Hospital / Long Beach Memorial; 🇺🇸 Long Beach, California, United States

Stanford University; 🇺🇸 Palo Alto, California, United States

University of California Davis Medical Center; 🇺🇸 Sacramento, California, United States

University of California San Francisco, Lung Transplant Program; 🇺🇸 San Francisco, California, United States

National Jewish Health; 🇺🇸 Denver, Colorado, United States

University of Miami Miller School of Medicine; 🇺🇸 Miami, Florida, United States

Central Florida Pulmonary Group, PA; 🇺🇸 Orlando, Florida, United States

Indiana University; 🇺🇸 Indianapolis, Indiana, United States

Scroll for more (83 remaining)