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

NCT ID: NCT03525548

Last Updated: 2020-01-27

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

113 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-08-03

Study Completion Date

2018-12-28

Brief Summary

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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

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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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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.

Group Type ACTIVE_COMPARATOR

TEZ/IVA

Intervention Type DRUG

Participants received TEZ/IVA orally once daily in the morning.

IVA

Intervention Type DRUG

Participants received IVA orally once daily in the evening.

Placebo

Intervention Type DRUG

Participants received placebo matched to VX-445/TEZ/IVA orally once daily in the morning.

VX-445/TEZ/IVA TC

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.

Group Type EXPERIMENTAL

VX-445/TEZ/IVA

Intervention Type DRUG

Participants received VX-445/TEZ/IVA orally once daily in the morning.

IVA

Intervention Type DRUG

Participants received IVA orally once daily in the evening.

Placebo

Intervention Type DRUG

Participants received placebo matched TEZ/IVA orally once daily in the morning.

Interventions

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VX-445/TEZ/IVA

Participants received VX-445/TEZ/IVA orally once daily in the morning.

Intervention Type DRUG

TEZ/IVA

Participants received TEZ/IVA orally once daily in the morning.

Intervention Type DRUG

IVA

Participants received IVA orally once daily in the evening.

Intervention Type DRUG

Placebo

Participants received placebo matched to VX-445/TEZ/IVA orally once daily in the morning.

Intervention Type DRUG

Placebo

Participants received placebo matched TEZ/IVA orally once daily in the morning.

Intervention Type DRUG

Other Intervention Names

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VX-445/VX-661/VX-770 VX-445/tezacaftor/ivacaftor VX-661/VX-770 tezacaftor/ivacaftor VX-770 ivacaftor

Eligibility Criteria

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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

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
Minimum Eligible Age

12 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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Banner University of Arizona Medical Center

Tucson, Arizona, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Miller Children's Hospital/ Long Beach Memorial

Long Beach, California, United States

Site Status

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

Valley Children's Hospital

Madera, California, United States

Site Status

National Jewish Health

Denver, Colorado, United States

Site Status

Joe DiMaggio Cystic Fibrosis & Pulmonary Center/ Joe DiMaggio Children's Hospital/ Memorial Regional Hospital

Hollywood, Florida, United States

Site Status

Central Florida Pulmonary Group, PA

Orlando, Florida, United States

Site Status

Nemours Children's Hospital

Orlando, Florida, United States

Site Status

Tampa General Hospital Cardiac and Lung Transplant Clinic

Tampa, Florida, United States

Site Status

Northwestern Memorial Hospital

Chicago, Illinois, United States

Site Status

Saint Francis Medical Center/ Children's Hospital of Illinoise/OSF

Peoria, Illinois, United States

Site Status

Tulane Medical Center

New Orleans, Louisiana, United States

Site Status

Massachusetts General Hospital Cystic Fibrosis Center Clinical Research Center

Boston, Massachusetts, United States

Site Status

Harper University Hospital

Detroit, Michigan, United States

Site Status

New York Medical College

Valhalla, New York, United States

Site Status

UNC Marisco Clinical Research Center

Chapel Hill, North Carolina, United States

Site Status

Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

Dayton Children's Hospital

Dayton, Ohio, United States

Site Status

ProMedica Toledo Hospital/ Toledo Children's Hospital/ Pediatric Pulmonary & Cystic Fibrosis Center

Toledo, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

The University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

Vermont Lung Center

Colchester, Vermont, United States

Site Status

University of Virginia Primary Care Center

Charlottesville, Virginia, United States

Site Status

West Virginia University

Morgantown, West Virginia, United States

Site Status

Cliniques Universitaires de Bruxelles Hopital Erasme

Brussels, , Belgium

Site Status

Universitair Ziekenhuis Brussel - Campus Jette

Brussels, , Belgium

Site Status

UZ Antwerpen

Edegem, , Belgium

Site Status

Universitair Ziekenhuis Gent

Ghent, , Belgium

Site Status

Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg

Leuven, , Belgium

Site Status

Academic Medical Center

Amsterdam, , Netherlands

Site Status

University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis

Heidelberglaan, , Netherlands

Site Status

UMC St. Radboud

Nijmegen, , Netherlands

Site Status

Erasmus Medical Center

Rotterdam, , Netherlands

Site Status

HagaZiekenhuis van den Haag

The Hague, , Netherlands

Site Status

The Royal Belfast Hospital for Sick Children

Belfast, , United Kingdom

Site Status

Heart of England NHS Foundation Trust, Birmingham Heartlands Hospital

Birmingham, , United Kingdom

Site Status

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

Exeter, , United Kingdom

Site Status

Leeds General Infirmary

Leeds, , United Kingdom

Site Status

King's College Hospital

London, , United Kingdom

Site Status

Southampton General Hospital

Southampton, , United Kingdom

Site Status

Countries

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United States Belgium Netherlands United Kingdom

References

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Heijerman HGM, McKone EF, Downey DG, Van Braeckel E, Rowe SM, Tullis E, Mall MA, Welter JJ, Ramsey BW, McKee CM, Marigowda G, Moskowitz SM, Waltz D, Sosnay PR, Simard C, Ahluwalia N, Xuan F, Zhang Y, Taylor-Cousar JL, McCoy KS; VX17-445-103 Trial Group. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1940-1948. doi: 10.1016/S0140-6736(19)32597-8. Epub 2019 Oct 31.

Reference Type DERIVED
PMID: 31679946 (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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2018-000184-89

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

VX17-445-103

Identifier Type: -

Identifier Source: org_study_id

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