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

March 29, 2021 updated by: Vertex Pharmaceuticals Incorporated

A Phase 2, Randomized, Double-blind, Controlled Study to Evaluate the Safety and Efficacy of VX-659 Combination Therapy in Subjects Aged 18 Years and Older With Cystic Fibrosis

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).

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.
124

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 2

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

  • Ireland
      • Cork, Ireland
        • Cork University Hospital
      • Dublin, Ireland
        • St. Vincent's University Hosptial
      • Galway, Ireland
        • Galway University Hospitals
      • Limerick, Ireland
        • University Hospital Limerick
  • Israel
      • Haifa, Israel
        • Carmel Medical Center
      • Haifa, Israel
        • Ruth Children's Hospital Rambam Health Care Campus
      • Jerusalem, Israel
        • Hadassah Medical Organization
      • Ramat Gan, Israel
        • The Chaim Sheba Medical Center
      • Tikvah, Israel
        • Schneider Children's Medical Center
  • United Kingdom
      • Birmingham, United Kingdom, B95SS
        • Birmingham Heartlands Hospital
      • Cambridge, United Kingdom
        • Papworth Hospital NHS Foundation Trust, Papworth Everard
      • Cardiff, United Kingdom
        • University Hospital Llandough in Cardiff
      • Devon, United Kingdom
        • Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital
      • Fulham, United Kingdom
        • The Newcastle upon Tyne Hospitals NHS Foundation Trust, The Royal Victoria Infirmary
      • Glasgow, United Kingdom
        • Greater Glasgow and Clyde NHS Board, Glasgow Clinical Research Facility
      • Hampshire, United Kingdom
        • Southampton University Hospitals NHS Foundation Trust
      • London, United Kingdom
        • Regional Respiratory Centre Belfast City Hospital
      • London, United Kingdom
        • Royal Brompton & Harefied NHS Foundation Trust
      • Manchester, United Kingdom
        • University Hospital of South Manchester NHS Trust, North West Lung Centre
      • Merseyside, United Kingdom
        • Liverpool Heart and Chest Hospital
      • Nottingham, United Kingdom
        • Nottingham University Hospitals NHS Trust
      • Nottingham, United Kingdom
        • Ruth Children's Hospital Rambam Health Care Campus
  • United States
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Yale New Haven Hospital
    • Florida
      • Miami, Florida, United States, 33136
        • University of Miami/Miller School of Medicine
    • Illinois
      • Morton Grove, Illinois, United States, 60053
        • Advocate Children's Hospital - Park Ridge / North Suburban Pulmonary and Critical Care Consultants
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Health
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • The University of Iowa Hospitals and Clinics
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • The Johns Hopkins Hospital/ Johns Hopkins Hospital, David Rubenstein Child Health Building
    • Massachusetts
      • Boston, Massachusetts, United States, 02155
        • 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
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Children's Mercy Hospital
    • New Jersey
      • New Brunswick, New Jersey, United States, 08902
        • Rutgers-Robert Wood Johnson Medical School/ Rutgers-Robert Wood Johnson Medical School, Clinical Research Center
    • New York
      • Albany, New York, United States, 12208
        • Albany Medical College
      • 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
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73112
        • Respiratory Diseases of Children & Adolescents
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15224
        • Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57104
        • 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, 37232
        • Vanderbilt University Medical Center
    • Utah
      • Salt Lake City, Utah, United States, 84014
        • 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

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Key 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

Key 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.

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
  • Masking: QUADRUPLE

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: 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.
Drug: Placebo (matched to VX-659/TEZ/IVA)
Placebo matched to VX-659 and TEZ/IVA.
EXPERIMENTAL: 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.
Drug: IVA
Tablet for oral administration.
Other Names:
  • VX-770
  • Ivacaftor
Drug: VX-659
Tablet for oral administration.
Drug: TEZ/IVA
TEZ/IVA fixed-dose combination tablet for oral administration.
Other Names:
  • VX-661/VX-770
  • Tezacaftor/Ivacaftor
EXPERIMENTAL: 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.
Drug: IVA
Tablet for oral administration.
Other Names:
  • VX-770
  • Ivacaftor
Drug: VX-659
Tablet for oral administration.
Drug: TEZ/IVA
TEZ/IVA fixed-dose combination tablet for oral administration.
Other Names:
  • VX-661/VX-770
  • Tezacaftor/Ivacaftor
EXPERIMENTAL: 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.
Drug: IVA
Tablet for oral administration.
Other Names:
  • VX-770
  • Ivacaftor
Drug: VX-659
Tablet for oral administration.
Drug: TEZ/IVA
TEZ/IVA fixed-dose combination tablet for oral administration.
Other Names:
  • VX-661/VX-770
  • Tezacaftor/Ivacaftor
ACTIVE_COMPARATOR: 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.
Drug: IVA
Tablet for oral administration.
Other Names:
  • VX-770
  • Ivacaftor
Drug: TEZ/IVA
TEZ/IVA fixed-dose combination tablet for oral administration.
Other Names:
  • VX-661/VX-770
  • Tezacaftor/Ivacaftor
EXPERIMENTAL: 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.
Drug: IVA
Tablet for oral administration.
Other Names:
  • VX-770
  • Ivacaftor
Drug: VX-659
Tablet for oral administration.
Drug: TEZ/IVA
TEZ/IVA fixed-dose combination tablet for oral administration.
Other Names:
  • VX-661/VX-770
  • Tezacaftor/Ivacaftor
PLACEBO_COMPARATOR: Part 3: Placebo
Participants received placebo matched to VX-659/TEZ/VX-561 in TC treatment period for 4 weeks.
Drug: Placebo (matched to VX-659/TEZ/VX-561)
Placebo matched to VX-659, TEZ and VX-561.
EXPERIMENTAL: 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.
Drug: TEZ
Tablet for oral administration.
Other Names:
  • VX-661
  • Tezacaftor
Drug: VX-561
Tablet for oral administration.
Other Names:
  • CTP-656
Drug: VX-659
Tablet for oral administration.

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
Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame: Day 1 Through Safety Follow-up (up to Day 61 for Part 1, Day 85 for Part 2 and Day 57 for Part 3)
Day 1 Through Safety Follow-up (up to Day 61 for Part 1, Day 85 for Part 2 and Day 57 for Part 3)
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Time Frame: From Baseline Through Day 29
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
From Baseline Through Day 29

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 Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
Time Frame: From Baseline at Day 29
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 Day 29
Absolute Change in Sweat Chloride Concentrations
Time Frame: From Baseline Through Day 29
Sweat samples were collected using an approved collection device.
From Baseline Through Day 29
Relative Change in ppFEV1
Time Frame: From Baseline Through Day 29
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
From Baseline Through Day 29
Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561
Time Frame: Pre-dose at Day 15 and Day 29
Pre-dose at Day 15 and Day 29

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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.
August 8, 2017

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 28, 2018

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 28, 2018

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).
July 18, 2017

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.
July 18, 2017

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.
July 21, 2017

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.
April 22, 2021

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 29, 2021

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.
February 1, 2021

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.
  • VX16-659-101
  • 2016-003585-11 (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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