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

NCT ID: NCT03224351

Last Updated: 2021-04-22

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

124 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-08-08

Study Completion Date

2018-02-28

Brief Summary

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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).

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Detailed Description

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Conditions

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Cystic Fibrosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Part 1: Placebo

Participants received placebo matched to VX-659/TEZ/IVA in TC treatment period for 4 weeks and placebo matched TEZ/IVA in washout period for 4 days.

Group Type PLACEBO_COMPARATOR

Placebo (matched to VX-659/TEZ/IVA)

Intervention Type DRUG

Placebo matched to VX-659 and TEZ/IVA.

Part 1: VX-659/TEZ/IVA TC - Low Dose

Participants received VX-659 80 milligram (mg) once daily (qd)/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days.

Group Type EXPERIMENTAL

VX-659

Intervention Type DRUG

Tablet for oral administration.

TEZ/IVA

Intervention Type DRUG

TEZ/IVA fixed-dose combination tablet for oral administration.

IVA

Intervention Type DRUG

Tablet for oral administration.

Part 1: VX-659/TEZ/IVA TC - Medium Dose

Participants received VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days.

Group Type EXPERIMENTAL

VX-659

Intervention Type DRUG

Tablet for oral administration.

TEZ/IVA

Intervention Type DRUG

TEZ/IVA fixed-dose combination tablet for oral administration.

IVA

Intervention Type DRUG

Tablet for oral administration.

Part 1: VX-659/TEZ/IVA TC - High Dose

Participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days.

Group Type EXPERIMENTAL

VX-659

Intervention Type DRUG

Tablet for oral administration.

TEZ/IVA

Intervention Type DRUG

TEZ/IVA fixed-dose combination tablet for oral administration.

IVA

Intervention Type DRUG

Tablet for oral administration.

Part 2: TEZ/IVA

Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks.

Group Type ACTIVE_COMPARATOR

TEZ/IVA

Intervention Type DRUG

TEZ/IVA fixed-dose combination tablet for oral administration.

IVA

Intervention Type DRUG

Tablet for oral administration.

Part 2: VX-659/TEZ/IVA TC

Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks.

Group Type EXPERIMENTAL

VX-659

Intervention Type DRUG

Tablet for oral administration.

TEZ/IVA

Intervention Type DRUG

TEZ/IVA fixed-dose combination tablet for oral administration.

IVA

Intervention Type DRUG

Tablet for oral administration.

Part 3: Placebo

Participants received placebo matched to VX-659/TEZ/VX-561 in TC treatment period for 4 weeks.

Group Type PLACEBO_COMPARATOR

Placebo (matched to VX-659/TEZ/VX-561)

Intervention Type DRUG

Placebo matched to VX-659, TEZ and VX-561.

Part 3: VX-659/TEZ/VX-561 TC

Participants received VX-659 400 mg qd/TEZ 100 mg qd/VX-561 200 mg qd in TC treatment period for 4 weeks.

Group Type EXPERIMENTAL

VX-659

Intervention Type DRUG

Tablet for oral administration.

TEZ

Intervention Type DRUG

Tablet for oral administration.

VX-561

Intervention Type DRUG

Tablet for oral administration.

Interventions

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VX-659

Tablet for oral administration.

Intervention Type DRUG

TEZ/IVA

TEZ/IVA fixed-dose combination tablet for oral administration.

Intervention Type DRUG

IVA

Tablet for oral administration.

Intervention Type DRUG

Placebo (matched to VX-659/TEZ/IVA)

Placebo matched to VX-659 and TEZ/IVA.

Intervention Type DRUG

TEZ

Tablet for oral administration.

Intervention Type DRUG

VX-561

Tablet for oral administration.

Intervention Type DRUG

Placebo (matched to VX-659/TEZ/VX-561)

Placebo matched to VX-659, TEZ and VX-561.

Intervention Type DRUG

Other Intervention Names

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VX-661/VX-770 Tezacaftor/Ivacaftor VX-770 Ivacaftor VX-661 Tezacaftor CTP-656

Eligibility Criteria

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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

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Vertex Pharmaceuticals Incorporated

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Yale New Haven Hospital

New Haven, Connecticut, United States

Site Status

University of Miami/Miller School of Medicine

Miami, Florida, United States

Site Status

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

Morton Grove, Illinois, United States

Site Status

Indiana University Health

Indianapolis, Indiana, United States

Site Status

The University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

The Johns Hopkins Hospital/ Johns Hopkins Hospital, David Rubenstein Child Health Building

Baltimore, Maryland, United States

Site Status

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, United States

Site Status

University of Michigan Health System

Ann Arbor, Michigan, United States

Site Status

Helen DeVos Children's Hospital CF Center

Grand Rapids, Michigan, United States

Site Status

Children's Mercy Hospital

Kansas City, Missouri, United States

Site Status

Rutgers-Robert Wood Johnson Medical School/ Rutgers-Robert Wood Johnson Medical School, Clinical Research Center

New Brunswick, New Jersey, United States

Site Status

Albany Medical College

Albany, New York, United States

Site Status

Northwell Health, Long Island Jewish Medical Center

New Hyde Park, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

SUNY Upstate Medical University

Syracuse, New York, United States

Site Status

Respiratory Diseases of Children & Adolescents

Oklahoma City, Oklahoma, United States

Site Status

Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

Sanford Research / USD

Sioux Falls, South Dakota, United States

Site Status

University of Tennessee Medical Center-Adult Cystic Fibrosis Clinic

Knoxville, Tennessee, United States

Site Status

Children's Foundation Research Center / Le Bonheur Children's Hospital

Memphis, Tennessee, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

University of Utah / Primary Children's Medical Center

Salt Lake City, Utah, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

Providence Pediatric Pulmonary & Allergy/Immunology Clinic

Spokane, Washington, United States

Site Status

Cork University Hospital

Cork, , Ireland

Site Status

St. Vincent's University Hosptial

Dublin, , Ireland

Site Status

Galway University Hospitals

Galway, , Ireland

Site Status

University Hospital Limerick

Limerick, , Ireland

Site Status

Carmel Medical Center

Haifa, , Israel

Site Status

Ruth Children's Hospital Rambam Health Care Campus

Haifa, , Israel

Site Status

Hadassah Medical Organization

Jerusalem, , Israel

Site Status

The Chaim Sheba medical center

Ramat Gan, , Israel

Site Status

Schneider Children's Medical Center

Tikvah, , Israel

Site Status

Birmingham Heartlands Hospital

Birmingham, , United Kingdom

Site Status

Papworth Hospital NHS Foundation Trust, Papworth Everard

Cambridge, , United Kingdom

Site Status

University Hospital Llandough in Cardiff

Cardiff, , United Kingdom

Site Status

Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital

Devon, , United Kingdom

Site Status

The Newcastle upon Tyne Hospitals NHS Foundation Trust, The Royal Victoria Infirmary

Fulham, , United Kingdom

Site Status

Greater Glasgow and Clyde NHS Board, Glasgow Clinical Research Facility

Glasgow, , United Kingdom

Site Status

Southampton University Hospitals NHS Foundation Trust

Hampshire, , United Kingdom

Site Status

Regional Respiratory Centre Belfast City Hospital

London, , United Kingdom

Site Status

Royal Brompton & Harefied NHS Foundation Trust

London, , United Kingdom

Site Status

University Hospital of South Manchester NHS Trust, North West Lung Centre

Manchester, , United Kingdom

Site Status

Liverpool Heart and Chest Hospital

Merseyside, , United Kingdom

Site Status

Nottingham University Hospitals NHS Trust

Nottingham, , United Kingdom

Site Status

Ruth Children's Hospital Rambam Health Care Campus

Nottingham, , United Kingdom

Site Status

Countries

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United States Ireland Israel United Kingdom

References

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Heneghan M, Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2023 Nov 20;11(11):CD010966. doi: 10.1002/14651858.CD010966.pub4.

Reference Type DERIVED
PMID: 37983082 (View on PubMed)

Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.

Reference Type DERIVED
PMID: 33331662 (View on PubMed)

Davies JC, Moskowitz SM, Brown C, Horsley A, Mall MA, McKone EF, Plant BJ, Prais D, Ramsey BW, Taylor-Cousar JL, Tullis E, Uluer A, McKee CM, Robertson S, Shilling RA, Simard C, Van Goor F, Waltz D, Xuan F, Young T, Rowe SM; VX16-659-101 Study Group. VX-659-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles. N Engl J Med. 2018 Oct 25;379(17):1599-1611. doi: 10.1056/NEJMoa1807119. Epub 2018 Oct 18.

Reference Type DERIVED
PMID: 30334693 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2016-003585-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

VX16-659-101

Identifier Type: -

Identifier Source: org_study_id

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