Study of VX-661 Alone and in Combination With Ivacaftor in Subjects Homozygous or Heterozygous to the F508del-Cystic Fibrosis Transmembrane Conductance Regulator(CFTR) Mutation

Vertex Pharmaceuticals Incorporated194 enrolled

Overview

The purpose of this study is to evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) effects of VX-661 alone and when coadministered with ivacaftor in participants with cystic fibrosis (CF) who are homozygous or heterozygous for the F508del-CFTR mutation.

This is a Phase 2, randomized, multicenter, double-blinded, placebo-controlled, study of VX-661 monotherapy, and VX-661/ivacaftor co-therapy in participants with CF who are homozygous or heterozygous for the F508del CFTR mutation. This study is separated into seven groups: Group 1-7, respectively. Approximately 180 participants were randomized in a ratio of 4:1; active drug to matching placebo in each group.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

194

Conditions

Cystic Fibrosis

Interventions

VX-661DRUG

IvacaftorDRUG

Placebo matched to VX-661DRUG

Placebo matched to ivacaftorDRUG

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Male or female with confirmed diagnosis of CF * Must have the F508del-CFTR gene mutation in both alleles (Groups 1, 2, 3, 4, 5, 6). Group 7 participants must have the F508del-CFTR mutation on 1 allele, and gating mutation G551D on the second allele and have been on their physician prescribed 150 mg KalydecoTM q12h (commercially available ivacaftor) for at least 28 days at the Screening Visit. * Forced expiratory volume in 1 second(FEV1) 40% to 90% (inclusive) of predicted normal for age, gender, and height (Knudson standards) at screening * Weight \>40 kg and BMI \>18.5 * Participants of child-bearing potential and who are sexually active must meet the contraception requirements. Exclusion Criteria: * History of any illness 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, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before Study Day 1. * History of solid organ or hematological transplantation * Participation in a clinical study involving administration of either an investigational or a marketed drug within 30 days or 5 terminal half-lives (whichever is longer) before screening * History of alcohol, medication, or illicit drug abuse within 1 year prior to screening * Pregnant, breast-feeding, or not willing to follow contraception requirements

Locations (36)

Outcomes

Primary Outcomes

Safety as Determined by Adverse Events (AEs)

An AE is defined as any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the Informed Consent Form is signed. AE includes serious as well as non-serious AEs. Serious Adverse Event (SAE) is any AE that results in any of the following: death; life-threatening condition; inpatient hospitalization or prolongation of hospitalization; persistent or significant disability or incapacity; congenital anomaly or birth defect; or other important medical event. Treatment-emergent adverse events are defined as adverse events that were reported or worsened on or after start of study drug through the Follow-up Visit (28 days after last dose of study drug) or premature discontinuation.

Time frame: Start of study drug through the Follow-up Visit (Up to Day 56)

Change in Sweat Chloride From Baseline Through Study Day 28 for Group 1-5b

Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug.

Time frame: Baseline through Day 28

Change in Sweat Chloride From Baseline Through Study Day 28 for Group 6

Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug. As per planned analysis, participants who received placebo in Group 4 and 6 were combined and compared with Group 6.

Time frame: Baseline through Day 28

Change in Sweat Chloride From Baseline Through Study Day 28 for Group 7

Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug.

Time frame: Baseline through Day 28

Secondary Outcomes

Data from ClinicalTrials.gov

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Vertex Investigational Site

Birmingham, Alabama, United States

Vertex Investigational Site

Oakland, California, United States

Vertex Investigational Site

Boise, Idaho, United States

Vertex Investigational Site

Chicago, Illinois, United States

Vertex Investigational Site

Boston, Massachusetts, United States

Vertex Investigational Site

Grand Rapids, Michigan, United States

Vertex Investigational Site

Kansas City, Missouri, United States

Vertex Investigational Site

Long Branch, New Jersey, United States

Vertex Investigational Site

New Hyde Park, New York, United States

Vertex Investigational Site

Chapel Hill, North Carolina, United States

...and 26 more locations

Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b

Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug.