A Phase 3 Study to Evaluate the Efficacy and Safety of Ivacaftor and VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Mutation

Vertex Pharmaceuticals Incorporated248 enrolled

Overview

The purpose of this study is to evaluate the efficacy and safety of VX-661 in combination with ivacaftor (IVA, VX-770) and IVA monotherapy in participants with Cystic Fibrosis (CF) who are heterozygous for F508del-CFTR allele and a second allele with a CFTR mutation predicted to have residual function.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

248

Conditions

Cystic Fibrosis

Interventions

VX-661/IvacaftorDRUG

Fixed dose combination tablet, oral use

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Heterozygous for F508del-CFTR and a second allele with a CFTR mutation predicted to have residual function * Forced Expiratory Volume in 1 Second (FEV1) greater than or equal to (≥) 40 percent (%) and less than or equal to (≤) 90% of predicted normal for age, sex, and height during screening * Sweat chloride value ≥60 millimole per liter (mmol/L) during screening OR as documented in the participant's medical record * Stable CF disease as judged by the investigator Exclusion Criteria: * History of any comorbidity that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the participant * An acute upper or lower respiratory infection, pulmonary exacerbation * History of solid organ or hematological transplantation * Ongoing or prior participation in an investigational drug study (including studies investigating VX-661, lumacaftor \[VX-809\], and/or ivacaftor) within 30 days of screening * Pregnant and nursing females * Sexually active participants of reproductive potential who are not willing to follow the contraception requirements

Locations (93)

Unnamed facility

Birmingham, Alabama, United States

Unnamed facility

Phoenix, Arizona, United States

Unnamed facility

Tucson, Arizona, United States

Unnamed facility

Long Beach, California, United States

Unnamed facility

Oakland, California, United States

Unnamed facility

Outcomes

Primary Outcomes

Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Average of Week 4 and Week 8

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

Time frame: Baseline, Week 4 and Week 8 of each treatment period

Secondary Outcomes

Absolute Change From Study Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Average of Week 4 and Week 8

The CFQ-R assessed respiratory symptoms on a scale with scores ranging from 0 to 100; where higher scores indicated fewer symptoms and better health-related quality of life.

Time frame: Baseline, Week 4 and Week 8 of each treatment period

Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time frame: Day 1 up to Week 28

Relative Change From Study Baseline in ppFEV1 at Average of Week 4 and Week 8

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

Time frame: Baseline, Week 4 and Week 8 of each treatment period

Absolute Change From Study Baseline in Sweat Chloride at Average of Week 4 and Week 8

Time frame: Baseline, Week 4 and Week 8 of each treatment period

Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1 VX-661), IVA and IVA Metabolite (M1 IVA) After Administration of VX-661/IVA Combination Therapy

Time frame: Pre-morning dose on Week 8 of each treatment period

Ctrough of IVA and IVA Metabolite (M1 IVA) After Administration of IVA Monotherapy

Time frame: Pre-morning dose on Week 8 of each treatment period