A Study Evaluating the Safety and Efficacy of VX-440 Combination Therapy in Subjects With Cystic Fibrosis

NCT ID: NCT02951182

Last Updated: 2020-08-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-31
• Study Completion Date: 2017-08-31

Brief Summary

This is a Phase 2, randomized, double-blind, placebo- and active-controlled, parallel group, multicenter study to evaluate the safety, tolerability, and efficacy of VX-440 in dual and triple combination with tezacaftor (TEZ; VX-661) and ivacaftor (IVA; VX-770) in subjects with cystic fibrosis (CF) who are homozygous for the F508del mutation of the CF transmembrane conductance regulator (CFTR) gene (F508del/F508del), or who are heterozygous for the F508del mutation and a minimal function (MF) CFTR mutation not likely to respond to TEZ and/or IVA therapy (F508del/MF).

Conditions

Cystic Fibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Part 1: Placebo - Cohort 1A and 1B Combined

Participants received placebo matched to VX-440/TEZ/IVA as triple combination for 4 weeks.

Group Type: PLACEBO_COMPARATOR

Matched Placebo

Intervention Type: DRUG

Part 1 Cohort 1A: Triple Combination (TC)

Participants received VX-440 200 milligram (mg) every 12 hours (q12h)/TEZ 100 mg once daily (qd)/IVA 150 mg q12h as triple combination for 4 weeks.

Group Type: EXPERIMENTAL

TEZ

Intervention Type: DRUG

IVA

Intervention Type: DRUG

VX-440

Intervention Type: DRUG

Part 1 Cohort 1B: TC Low Dose

Participants received VX-440 200 mg q12h/TEZ 50 mg q12h/IVA 150 mg q12h as triple combination for 4 weeks.

Group Type: EXPERIMENTAL

TEZ

Intervention Type: DRUG

IVA

Intervention Type: DRUG

VX-440

Intervention Type: DRUG

Part 1 Cohort 1B: TC High Dose

Participants received VX-440 600 mg q12h/TEZ 50 mg q12h/IVA 300 mg q12h as triple combination for 4 weeks.

Group Type: EXPERIMENTAL

TEZ

Intervention Type: DRUG

IVA

Intervention Type: DRUG

VX-440

Intervention Type: DRUG

Part 2: TEZ/IVA

Following a 4-week run-in period on TEZ 100 mg qd/IVA150 mg q12h, participants received placebo matched to VX-440 and TEZ 50 mg q12h/IVA 300 mg q12h for 4 weeks in treatment period and TEZ 100 mg qd/IVA150 mg q12h for 4 weeks in washout period.

Group Type: ACTIVE_COMPARATOR

TEZ

Intervention Type: DRUG

IVA

Intervention Type: DRUG

Matched Placebo

Intervention Type: DRUG

Part 2: TC-2

Following a 4-week run-in period on TEZ 100 mg qd/IVA150 mg q12h, participants received VX-440 600 mg q12h/ TEZ 50 mg q12h/IVA 300 mg q12h for 4 weeks for 4 weeks in treatment period and TEZ 100 mg qd/IVA150 mg q12h for 4 weeks in washout period.

Group Type: EXPERIMENTAL

TEZ

Intervention Type: DRUG

IVA

Intervention Type: DRUG

VX-440

Intervention Type: DRUG

Interventions

TEZ

Intervention Type: DRUG

IVA

Intervention Type: DRUG

VX-440

Intervention Type: DRUG

Matched Placebo

Intervention Type: DRUG

Other Intervention Names

tezacaftor; VX-661; ivacaftor; VX-770

Eligibility Criteria

Inclusion Criteria

• Willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.
• To prevent pregnancy, female participants of childbearing potential and their male partners will be required to use pre-specified, highly effective methods of non-hormonal contraception. Male participants with female partners of childbearing potential will be required to use a condom.
• Body weight ≥35 kg.
• Sweat chloride value ≥60 mmol/L from test results obtained during screening.
• Subjects must have an eligible CFTR genotype:

• Heterozygous for F508del and a minimal function (MF) mutation known or predicted not to be responsive to TEZ and/or IVA.
• Homozygous for F508del
• Subjects must have an FEV1 ≥40% and ≤90% of predicted normal for age, sex, and height at the Screening Visit
• Stable CF disease as judged by the investigator.
• Willing to remain on a stable CF medication regimen through the planned end of treatment or, if applicable, the Safety Follow up Visit.

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 subject.
• History of cirrhosis with portal hypertension.
• Risk factors for Torsade de Pointes
• History of hemolysis.
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency assessed at Screening.
• Clinically significant abnormal laboratory values at screening
• An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 28 days before the first dose of study drug.
• Lung infection with organisms associated with a more rapid decline in pulmonary status
• An acute illness not related to CF within 14 days before the first dose of study drug
• A standard digital ECG demonstrating QTc >450 msec at screening.
• History of solid organ or hematological transplantation.
• History or evidence of cataract or lens opacity determined to be clinically significant by the ophthalmologist or optometrist based on the ophthalmologic examination during the Screening Period.
• History of alcohol or drug abuse in the past year, including but not limited to, cannabis, cocaine, and opiates, as deemed by the investigator.
• Ongoing or prior participation in an investigational drug study, with certain exceptions. (e.g., ongoing participation in NCT02565914)
• Use of commercially available CFTR modulator (e.g., Kalydeco, Orkambi) within 14 days before screening (applies only to the Heterozygous F508del/MF cohorts; does not apply to the Homozygous F508del/F508del Cohort).
• Pregnant or nursing females: Females of childbearing potential must have a negative pregnancy test at screening and Day 1.

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vertex Pharmaceuticals Incorporated

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

The Arizona Board of Regents on behalf of the University of Arizona

Tucson, Arizona, United States

Stanford University

Palo Alto, California, United States

University of California

San Francisco, California, United States

National Jewish Health

Denver, Colorado, United States

Joe Di Maggio Cystic Fibrosis & Pulmonary Center

Hollywood, Florida, United States

Central Florida Pulmonary Group

Orlando, Florida, United States

St. Luke's CF Center of Idaho

Boise, Idaho, United States

Cystic Fibrosis Center of Chicago

Glenview, Illinois, United States

The Johns Hopkins Hospital

Baltimore, Maryland, United States

Boston Children's Hospital

Boston, Massachusetts, United States

Massachusetts General Hospital Cystic Fibrosis Center

Boston, Massachusetts, United States

University of Minnesota

Minneapolis, Minnesota, United States

New York Medical College

Hawthorne, New York, United States

Long Island Jewish Medical Center

New Hyde Park, New York, United States

Columbia University Medical Center

New York, New York, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

Respiratory Diseases of Children and Adolescents

Oklahoma City, Oklahoma, United States

UPMC OSPARS Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Sanford Children's Specialty Clinic Sanford Research USD

Sioux Falls, South Dakota, United States

The University of Texas Southwestern Center

Dallas, Texas, United States

Children's Hospital of the Kings Daughters

Norfolk, Virginia, United States

Seattle Children's Hospital

Seattle, Washington, United States

Royal Adelaide Hospital

Adelaide, , Australia

Prince Charles Hospital

Chermside, , Australia

John Hunter Hospital & Hunter Medical Research Institute

New Lambton Heights, , Australia

Medizinische Universitat Innsbruck

Innsbruck, , Austria

Universitair Ziekenhuis Brussel

Brussels, , Belgium

Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg

Leuven, , Belgium

St. Paul's Hopsital

Vancouver, British Columbia, Canada

St. Michael's Hospital

Toronto, Ontario, Canada

Juliane Marie Center, Righospitalet

Copenhagen, , Denmark

University Hospital Cologne

Cologne, , Germany

Mukeviszidose-Zentrum am Universtitatsklinikum Jena

Jena, , Germany

Pneumologische Praxis Pasing

München, , Germany

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, , Italy

Hospital Universitari Vall d´Hebron Servicio de Broncoscopia

Barcelona, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

Heart of England NHS Foundation Trust

Birmingham, , United Kingdom

Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital

London, , United Kingdom

Southampton University Hospitals NHS Foundation Trust

Southampton, , United Kingdom

Countries

United States; Australia; Austria; Belgium; Canada; Denmark; Germany; Italy; Spain; United Kingdom

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

2016-000454-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

VX15-440-101

Identifier Type: -

Identifier Source: org_study_id