A Study Evaluating the Safety and Efficacy of VX-659 Combination Therapy in Subjects With Cystic Fibrosis

Vertex Pharmaceuticals Incorporated124 enrolled

Overview

This is a Phase 2, randomized, double-blind, placebo- and tezacaftor/ivacaftor (TEZ/IVA)-controlled, parallel-group, 3-part, multicenter study designed to evaluate the safety and efficacy of VX-659 in triple combination (TC) with TEZ and IVA in subjects with cystic fibrosis (CF) who are homozygous for the F508del mutation of the CF transmembrane conductance regulator (CFTR) gene (F/F genotype), or who are heterozygous for the F508del mutation and a minimal function (MF) CFTR mutation not likely to respond to TEZ, IVA, or TEZ/IVA (F/MF genotypes).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

124

Conditions

Cystic Fibrosis

Interventions

VX-659

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Body weight ≥35 kg. * Subjects must have an eligibleCFTR genotype. * Part 1 and Part 3: Heterozygous for F508del and an MF mutation (F/MF) * Part 2: Homozygous for F508del (F/F) * FEV1 value ≥40% and ≤90% of predicted mean for age, sex, and height Key Exclusion Criteria: * History of clinically significant cirrhosis with or without portal hypertension. * Glucose-6-phosphate dehydrogenase (G6PD) deficiency * Lung infection with organisms associated with a more rapid decline in pulmonary status. * History of solid organ or hematological transplantation. Other protocol defined Inclusion/Exclusion criteria may apply.

Locations (47)

Yale New Haven Hospital

New Haven, Connecticut, United States

University of Miami/Miller School of Medicine

Miami, Florida, United States

Advocate Children's Hospital - Park Ridge / North Suburban Pulmonary and Critical Care Consultants

Morton Grove, Illinois, United States

Indiana University Health

Indianapolis, Indiana, United States

The University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Outcomes

Primary Outcomes

Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Time frame: Day 1 Through Safety Follow-up (up to Day 61 for Part 1, Day 85 for Part 2 and Day 57 for Part 3)

Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)

FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

Time frame: From Baseline Through Day 29

Secondary Outcomes

Absolute Change in Sweat Chloride Concentrations

Sweat samples were collected using an approved collection device.

Time frame: From Baseline Through Day 29

Relative Change in ppFEV1

FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

Time frame: From Baseline Through Day 29

Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score

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.

Time frame: From Baseline at Day 29

Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561

Time frame: Pre-dose at Day 15 and Day 29