A Phase 3 Study of VX-659 Combination Therapy in Subjects With Cystic Fibrosis Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)

March 12, 2020 updated by: Vertex Pharmaceuticals Incorporated

A Phase 3, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-659 Combination Therapy in Subjects With Cystic Fibrosis Who Are Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)

This study will evaluate the efficacy of VX-659 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are heterozygous for F508del and a minimal function mutation (F/MF subjects).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
385

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Adelaide, Australia
        • Royal Adelaide Hospital
      • Chermside, Australia
        • Prince Charles Hospital
      • Herston, Australia
        • Royal Brisbane & Women's Hospital
      • Nedlands, Australia
        • Institute for Respiratory Health Inc./ Sir Charles Gairdner Hospital
      • New Lambton Heights, Australia
        • John Hunter Hospital & Hunter Medical Research Institute
      • Randwick, Australia
        • Sydney Children's Hospital, Randwick
      • Subiaco, Australia
        • Princess Margaret Hospital for Children
    • Victoria
      • Melbourne, Victoria, Australia
        • The Alfred Hospital
  • Canada
      • Toronto, Canada
        • St. Michael's Hospital
    • Alberta
      • Edmonton, Alberta, Canada
        • Stollery Children's Hospital
    • Nova Scotia
      • Halifax, Nova Scotia, Canada
        • Queen Elizabeth II Health Sciences Center
  • Denmark
      • Copenhagen, Denmark
        • Juliane Marie Center, Rigshospitalet
  • Germany
      • Berlin, Germany
        • Charite Paediatric Pulmonology Department
      • Essen, Germany
        • Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen
      • Frankfurt, Germany
        • Clinic of J.W Goethe University
      • Hannover, Germany
        • Medizinische Hochschule Hannover
      • Jena, Germany
        • Mukeviszidose-Zentrum am Universitatsklinikum Jena, Klinik fuer Kinder - und Jugendmedizin
      • Koeln, Germany
        • University Hospital Cologne
      • Lubeck, Germany
        • Universitatsklinikum Schleswig-Holstein, Klinik für Kinder- und Jugendmedizin
      • Muenchen, Germany
        • Pneumologische Praxis Pasing
      • München, Germany
        • Klinikum Innenstadt, University of Munich
  • Ireland
      • Dublin, Ireland
        • Beaumont Hospital
      • Dublin, Ireland
        • St. Vincent's University Hospital
      • Dublin, Ireland
        • Our Lady's Children's Hospital
      • Dublin, Ireland
        • Children's University Hospital Temple Street
      • Dublin, Ireland
        • Cork University Hospital
      • Galway, Ireland
        • National University of Ireland
      • Limerick, Ireland
        • University Hospital Limerick
  • Israel
      • Haifa, Israel
        • Lady Davis Carmel Medical Center
      • Haifa, Israel
        • Pediatric Pulmonary Unit Rambam Medical Center
      • Jerusalem, Israel
        • Hadassah Medical Organization
      • Petah tikva, Israel
        • Schneider Children's Medical Center
      • Tel HaShomer, Israel
        • Sheba Medical Center
  • Poland
      • Warsaw, Poland
        • Instytut Matki i Dziecka
  • Spain
      • Barcelona, Spain
        • Hospital Universitari Vall d Hebron
      • Barcelona, Spain
        • Hospital Universitari Vall d'Hebron Servicio de Broncoscopia
      • Madrid, Spain
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain
        • Hospital Universitario Infantil LA PAZ
      • Sabadell, Spain
        • Coporacio Sanitaria Parc Tauli
      • Sevilla, Spain
        • Hospital Universitario Virgen del Rocio
      • Valencia, Spain
        • Hospital Universitario y Politécnico La Fe
  • Switzerland
      • Bern, Switzerland
        • Lindenhofspital - Quartier Bleu
      • Zürich, Switzerland
        • Universitaetsspital Zuerich
      • Zürich, Switzerland
        • Kinderspital Zuerich
  • United Kingdom
      • Cambridge, United Kingdom
        • Papworth Hospital NHS Foundation Trust, Papworth Everard
      • Glasgow, United Kingdom
        • Queen Elizabeth University Hospital
      • Leeds, United Kingdom
        • The Leeds Teaching Hospitals NHS Trust, St. James University Hospital
      • Liverpool, United Kingdom
        • Liverpool Heart and Chest Hospital
      • London, United Kingdom
        • Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital
      • Manchester, United Kingdom
        • Wythenshawe Hospital
      • Newcastle Upon Tyne, United Kingdom
        • The Newcastle upon Tyne Hospitals NHS Foundation Trust, The Royal Victoria Infirmary
      • Nottingham, United Kingdom
        • Nottingham University Hospitals NHS Trust, Queens Medical Center
      • Penarth, United Kingdom
        • University Hospital Llandough
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham
    • California
      • Palo Alto, California, United States, 94304
        • Stanford University
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Children's Hospital Colorado
    • Connecticut
      • Hartford, Connecticut, United States, 06106
        • Hartford Health
      • New Haven, Connecticut, United States, 06511
        • Yale New Haven Medical Center
    • Florida
      • Miami, Florida, United States, 33155
        • Nicklaus Children's Hospital
      • Miami, Florida, United States, 33136
        • University of Miami/ Miller School of Medicine
      • Orlando, Florida, United States, 32806
        • Arnold Palmer Hospital
      • Saint Petersburg, Florida, United States, 33701
        • Johns Hopkins All Children's Hospital Outpatient Care Center
    • Idaho
      • Boise, Idaho, United States, 83712
        • St. Luke's CF Center of Idaho
    • Illinois
      • Glenview, Illinois, United States, 60025
        • Cystic Fibrosis Center of Chicago
      • Niles, Illinois, United States, 60714
        • Advocate Children's Hospital - Park Ridge/ North Suburban Pulmonary and Critical Care Consultants
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana Clinical Research Center, IU Health University Hospital
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • The University of Iowa Hospitals and Clinics
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • Kentucky Clinic
      • Louisville, Kentucky, United States, 40202
        • Kosair Charities Pediatric Clinical Research Unit
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • The Johns Hopkins Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Boston Children's Hospital
      • Worcester, Massachusetts, United States, 01655
        • University of Massachusetts Memorial Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Health System
      • Grand Rapids, Michigan, United States, 49503
        • Helen DeVos Children's Hospital CF Center
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • University of Mississippi Medical Center
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Children's Mercy Hospital
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine/ St. Louis Children's Hospital
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth Hitchcock Medical Center, Lebanon
    • New Jersey
      • New Brunswick, New Jersey, United States, 80901
        • Rutgers-Robert Wood Johnson Medical School
    • New York
      • Albany, New York, United States, 12208
        • Albany Medical College
      • Buffalo, New York, United States, 14222
        • Lung and Cystic Fibrosis Center at Women and Children's Hospital of Buffalo
      • New Hyde Park, New York, United States, 11040
        • Northwell Health, Long Island Jewish Medical Center
      • New York, New York, United States, 10032
        • Columbia University Medical Center
      • Syracuse, New York, United States, 13210
        • SUNY Upstate Medical University
    • North Carolina
      • Charlotte, North Carolina, United States, 28277
        • Clinical Research of Charlotte
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73112
        • Respiratory Diseases of Children and Adolescents
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health & Science University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19017
        • Drexel University College of Medicine/ Drexel Adult Cystic Fibrosis Center
      • Pittsburgh, Pennsylvania, United States, 15224
        • Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57105
        • Sanford Research/ USD
    • Tennessee
      • Knoxville, Tennessee, United States, 37920
        • University of Tennessee Medical Center - Adult Cystic Fibrosis Clinic
      • Memphis, Tennessee, United States, 38103
        • Children's Foundation Research Center/ Le Bonheur Children's Hospital
      • Nashville, Tennessee, United States, 37920
        • Vanderbilt University Medical Center
    • Texas
      • Fort Worth, Texas, United States, 76104
        • Cook Children's Medical Center
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah / Primary Children's Medical Center
    • Washington
      • Seattle, Washington, United States, 98105
        • Seattle Children's Hospital
      • Spokane, Washington, United States, 99204
        • Providence Pediatric Pulmonary & Allergy/Immunology Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Key Inclusion Criteria:

  • Heterozygous for F508del and an MF mutation (as defined in the protocol)
  • Forced expiratory volume in 1 second (FEV1) value ≥40% and ≤90% of predicted mean for age, sex, and height

Key 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

Other protocol defined Inclusion/Exclusion criteria may apply

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
Participants who received placebo matched to VX-659/TEZ/IVA for 24 weeks in the TC treatment period.
Drug: Placebo
Participants received placebo matched VX-659/TEZ/IVA orally once daily in the morning and placebo matched to IVA orally once daily in the evening.
Experimental: VX-659/TEZ/IVA TC
Participants who received VX-659 240 mg/TEZ 100 mg/IVA 150 mg as fixed-dose combination (FDC) tablets in the morning and IVA 150 mg as mono tablet in the evening for 24 weeks in the TC treatment period.
Drug: VX-659/TEZ/IVA
Participants received VX-659/TEZ/IVA orally once daily in the morning.
Other Names:
  • VX-659/VX-661/VX-770
  • VX-659/tezacaftor/ivacaftor
Drug: IVA
Participants received IVA orally once daily in the evening.
Other Names:
  • VX-770
  • ivacaftor

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Time Frame: From Baseline at Week 4
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
From Baseline at Week 4

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Time Frame: From Baseline through Week 24
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
From Baseline through Week 24
Number of Pulmonary Exacerbations (PEx)
Time Frame: From Baseline through Week 24
Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
From Baseline through Week 24
Absolute Change in Sweat Chloride (SwCl)
Time Frame: From Baseline through Week 24
Sweat samples were collected using an approved collection device.
From Baseline through Week 24
Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score
Time Frame: From Baseline through Week 24
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
From Baseline through Week 24
Absolute Change in Body Mass Index (BMI)
Time Frame: From Baseline at Week 24
BMI was defined as weight in kilogram (kg) divided by height in square meter (m^2).
From Baseline at Week 24
Absolute Change in Sweat Chloride
Time Frame: From Baseline at Week 4
Sweat samples were collected using an approved collection device.
From Baseline at Week 4
Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score
Time Frame: From Baseline at Week 4
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
From Baseline at Week 4
Time-to-first Pulmonary Exacerbation (PEx)
Time Frame: From Baseline through Week 24
Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
From Baseline through Week 24
Absolute Change in BMI Z-score for Participants <=20 Years of Age at Baseline
Time Frame: From Baseline at Week 24
BMI was defined as weight in kg divided by height in m^2. z-score is a statistical measure to describe whether a mean was above or below the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of higher BMI.
From Baseline at Week 24
Absolute Change in Body Weight
Time Frame: From Baseline at Week 24
From Baseline at Week 24
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 28 weeks)
From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 28 weeks)
Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, and IVA
Time Frame: Pre-dose on Week 4, 8, 12, and 16
Pre-dose on Week 4, 8, 12, and 16

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Vertex Pharmaceuticals Incorporated

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 7, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 5, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 5, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 21, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 21, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 27, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 13, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 12, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • VX17-659-102
  • 2017-004132-11 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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