A Study of VX-445 Combination Therapy in CF Subjects Homozygous for F508del (F/F)

Phase 3

Completed

• Conditions: Cystic Fibrosis
• Interventions: Drug: TEZ/IVA; Drug: VX-445/TEZ/IVA; Drug: IVA; Drug: Placebo

• Registration Number: NCT03525548
• Lead Sponsor: Vertex Pharmaceuticals Incorporated

Brief Summary

This study will evaluate the efficacy of VX-445 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are homozygous for the F508del mutation (F/F)

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-05-02
• Study First Submitted QC: 2018-05-02
• Study First Posted: 2018-05-15
• Study Start: 2018-08-03
• Primary Completion: 2018-12-28
• Study Completion: 2018-12-28
• Results First Submitted: 2019-12-20
• Status Verified: 2020-01
• Results First Submitted QC: 2020-01-24
• Last Update Submitted: 2020-01-24
• Results First Posted: 2020-01-27
• Last Update Posted: 2020-01-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 113

Inclusion Criteria

• Homozygous for the F508del mutation (F/F)
• 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
TEZ/IVA	TEZ/IVA	Following a run-in period of 4 weeks with Tezacaftor (TEZ)/Ivacaftor (IVA), participants received TEZ 100 milligram (mg)/IVA 150 mg as fixed-dose combination (FDC) tablet in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the triple combination (TC) treatment period.
TEZ/IVA	Placebo	Following a run-in period of 4 weeks with Tezacaftor (TEZ)/Ivacaftor (IVA), participants received TEZ 100 milligram (mg)/IVA 150 mg as fixed-dose combination (FDC) tablet in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the triple combination (TC) treatment period.
VX-445/TEZ/IVA TC	Placebo	Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-445 200 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period.
TEZ/IVA	IVA	Following a run-in period of 4 weeks with Tezacaftor (TEZ)/Ivacaftor (IVA), participants received TEZ 100 milligram (mg)/IVA 150 mg as fixed-dose combination (FDC) tablet in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the triple combination (TC) treatment period.
VX-445/TEZ/IVA TC	VX-445/TEZ/IVA	Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-445 200 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period.
VX-445/TEZ/IVA TC	IVA	Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-445 200 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period.

Primary Outcome Measures

Name	Time	Method
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)	From Baseline at Week 4	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

Secondary Outcome Measures

Name	Time	Method
Observed Pre-Dose Concentration (Ctrough) of VX-445, TEZ, TEZ Metabolite (M1-TEZ), and IVA	Day 1 and Week 4
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)
Absolute Change in Sweat Chloride (SwCl)	From Baseline at Week 4	Sweat samples were collected using an approved collection device.
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score	From Baseline at Week 4	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 indicate fewer symptoms and better health-related quality of life.

Trial Locations

Locations (44)

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

University of Arkansas for Medical Sciences; 🇺🇸 Little Rock, Arkansas, United States

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

Children's Hospital Los Angeles; 🇺🇸 Los Angeles, California, United States

Valley Children's Hospital; 🇺🇸 Madera, California, United States

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

Joe DiMaggio Cystic Fibrosis & Pulmonary Center/ Joe DiMaggio Children's Hospital/ Memorial Regional Hospital; 🇺🇸 Hollywood, Florida, United States

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

Nemours Children's Hospital; 🇺🇸 Orlando, Florida, United States

Tampa General Hospital Cardiac and Lung Transplant Clinic; 🇺🇸 Tampa, Florida, United States

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