A Study to Evaluate Safety, Efficacy, and Tolerability of TEZ/IVA in Orkambi® (Lumacaftor/Ivacaftor) -Experienced Subjects With Cystic Fibrosis (CF)

NCT ID: NCT03150719

Last Updated: 2019-09-12

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

98 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-05-24

Study Completion Date

2018-08-09

Brief Summary

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Study VX16-661-114 (Study 114) is a Phase 3b, randomized, double-blind, placebo-controlled, parallel-group, multicenter study in subjects aged 12 years and older with CF who are homozygous for the F508del mutation on the cystic fibrosis transmembrane conductance regulator gene (CFTR) gene and who discontinued treatment with Orkambi due to respiratory symptoms considered related to treatment. This study is designed to evaluate the safety and efficacy of Tezacaftor/Ivacaftor (TEZ/IVA).

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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Placebo

Participants received placebo matched to TEZ/IVA fixed-dose combination tablet orally once daily in the morning followed by placebo matched to IVA tablet orally once daily in the evening for 56 days.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo matched to TEZ/IVA fixed-dose combination tablet.

Placebo

Intervention Type DRUG

Placebo matched to IVA tablet.

TEZ/IVA

Participants received TEZ 100 milligram (mg)/IVA 150 mg fixed-dose combination tablet orally once daily in the morning and IVA 150 mg tablet orally once daily in the evening for 56 days.

Group Type EXPERIMENTAL

Tezacaftor/Ivacaftor

Intervention Type DRUG

TEZ 100 mg/IVA 150 mg fixed-dose combination tablet.

Ivacaftor

Intervention Type DRUG

IVA 150 mg tablet.

Interventions

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Tezacaftor/Ivacaftor

TEZ 100 mg/IVA 150 mg fixed-dose combination tablet.

Intervention Type DRUG

Ivacaftor

IVA 150 mg tablet.

Intervention Type DRUG

Placebo

Placebo matched to TEZ/IVA fixed-dose combination tablet.

Intervention Type DRUG

Placebo

Placebo matched to IVA tablet.

Intervention Type DRUG

Other Intervention Names

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TEZ/IVA; VX-661/VX-770 VX-770; IVA

Eligibility Criteria

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Inclusion Criteria

* Willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.
* Prior discontinuation of Orkambi, with at least 1 respiratory sign or symptom considered related to therapy.
* Resolution or stabilization of qualifying event(s) \>28 days prior to Screening.
* Discontinuation of Orkambi therapy must have occurred within approximately 12 weeks from the first dose of Orkambi.
* Homozygous for F508del mutation in the CFTR gene as documented in the subject's medical record. If genotype documentation is not available in the medical record, genotyping will be performed during screening.
* FEV1 ≥25% and ≤90% of predicted normal for age, sex, and height.
* 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 subject.
* Recent rapid or progressive deterioration in respiratory status.
* Receiving continuous oxygen at \>2L/min or on face-mask ventilation.
* Any protocol-defined exclusionary laboratory values at Screening.
* Child-Pugh Class B or C hepatic impairment.
* An acute upper or lower respiratory infection, pulmonary exacerbation, or change in therapy for pulmonary disease within 28 days before Day 1.
* Documentation of colonization with organisms associated with a more rapid decline in pulmonary status.
* History of lung transplantation since most recent initiation of Orkambi.
* History of alcohol or drug abuse in the past year as deemed by the investigator.
* Participation in an investigational drug study or use of a CFTR modulator within 28 days or 5 terminal half-lives of the investigational drug or modulator (whichever is longer).
* Use of restricted medications or foods within the specified window before the first dose of study drug, or an anticipated need or use of restricted medication or foods after the first dose of study drug.
* Pregnant or nursing females: Females of child-bearing 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

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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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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Phoenix Children's Hospital

Phoenix, Arizona, United States

Site Status

UCSF - Fresno, Community Regional Medical Center

Fresno, California, 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

Rady Children's Hospital

San Diego, California, United States

Site Status

National Jewish Health

Denver, Colorado, United States

Site Status

Yale New Haven Hospital

New Haven, Connecticut, United States

Site Status

Central Florida Pulmonary Group

Orlando, Florida, United States

Site Status

Arnold Palmer Hospital

Orlando, Florida, United States

Site Status

Tampa General Hospital Cardiac and Lung Transplant Clinic

Tampa, Florida, United States

Site Status

Children's Speciality Services at North Druid Hills

Atlanta, Georgia, United States

Site Status

St. Luke's CF Center of Idaho

Boise, Idaho, United States

Site Status

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

Niles, Illinois, United States

Site Status

Southern Illinois University

Springfield, Illinois, United States

Site Status

Riley Hospital for Children at Indiana University Health

Indianapolis, Indiana, United States

Site Status

The University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

Kentucky Clinic

Lexington, Kentucky, United States

Site Status

Tulane Medical Center

New Orleans, Louisiana, United States

Site Status

Massachusetts General Hospital Cystic Fibrosis Center

Boston, Massachusetts, United States

Site Status

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Children's Mercy Hospital

Kansas City, Missouri, United States

Site Status

Billings Clinic

Billings, Montana, United States

Site Status

Mount Sinai Beth Israel

New York, New York, United States

Site Status

New York Medical College

Valhalla, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, United States

Site Status

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Santiago Reyes, M.D.

Oklahoma City, Oklahoma, United States

Site Status

Drexel University College of Medicine/ Drexel Adult Cystic Fibrosis Center

Philadelphia, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

The University of Tennessee Medical Center

Nashville, Tennessee, United States

Site Status

Dell Children's Medical Center of Central Texas

Austin, Texas, United States

Site Status

The University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

University of Utah / Primary Children's Medical Center

Salt Lake City, Utah, United States

Site Status

Children's Hospital of the King's Daughters

Norfolk, Virginia, United States

Site Status

Children's Hospital of Richmond at VCU, Children's Pavilion

Richmond, Virginia, United States

Site Status

Centre Hospitalier Intercommunal de Créteil

Créteil, , France

Site Status

Centre Hospitalier Universitaire De Grenoble - Hopital Michallon

Grenoble, , France

Site Status

CHU de Montpellier - Hopital Arnaud de Villeneuve

Montpellier, , France

Site Status

Centre Hospitalier Universitaire De Nantes

Nantes, , France

Site Status

Centre hospitalier universitaire de Nice, Pulmonology

Nice, , France

Site Status

Hopital Cochin

Paris, , France

Site Status

Centre Hospitalier Universitaire - Hopitaux de Rouen

Rouen, , France

Site Status

Charite Paediatric Pulmonology Department

Berlin, , Germany

Site Status

Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen

Essen, , Germany

Site Status

Klinikum Innenstadt, University of Munich

München, , Germany

Site Status

Pneumologische Praxis Pasing

München, , Germany

Site Status

Universitaetsklinikum Tuebingen Klinik fuer Kinder- und Jugendmedizin

Tübingen, , Germany

Site Status

Countries

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United States France Germany

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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2017-000540-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

VX16-661-114

Identifier Type: -

Identifier Source: org_study_id

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