A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of VX-661 in Combination With Ivacaftor

May 8, 2018 updated by: Vertex Pharmaceuticals Incorporated

A Phase 3, Randomized, Double Blind, Placebo Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Homozygous for the F508del CFTR Mutation

This is a Phase 3, randomized, double blind, placebo controlled, parallel group, multicenter study in people with cystic fibrosis (CF) who are homozygous for the F508del CF transmembrane conductance regulator (CFTR) gene mutation.

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.

Detailed Description

This is a Phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter study in people with CF who are homozygous for the F508del-CFTR mutation. This study is designed to evaluate the efficacy and safety of VX-661 in combination with Ivacaftor (IVA, VX-770). The active treatment regimen comprised of a morning dose of a fixed-dose combination (FDC) tablet of 100 milligram (mg) VX-661/150 mg IVA once daily (qd) and an evening dose of IVA 150 mg to be taken approximately 12 hours after the morning dose. The placebo regimen was visually matched tablets to be taken with the same schedule as the active treatment.

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.
510

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

  • Canada
    • Alberta
      • Calgary, Alberta, Canada
    • British Columbia
      • Vancouver, British Columbia, Canada
    • Nova Scotia
      • Halifax, Nova Scotia, Canada
    • Ontario
      • Toronto, Ontario, Canada
    • Quebec
      • Montreal, Quebec, Canada
  • Denmark
      • Copenhagen O, Denmark
  • France
    • Bouches-du-Rhone
      • Marseille cedex 20, Bouches-du-Rhone, France
    • Finistere
      • Roscoff, Finistere, France
    • Girande
      • Bordeaux, Girande, France
    • Nord
      • Lille Cedex, Nord, France
    • Paris
      • Paris Cedex 19, Paris, France
      • Paris cedex 14, Paris, France
    • Rhone
      • Pierre Benite cedex, Rhone, France
  • Germany
      • Berlin, Germany
    • Baden Wuerttemberg
      • Heidelberg, Baden Wuerttemberg, Germany
    • Bayern
      • Muenchen, Bayern, Germany
      • Wuerzburg, Bayern, Germany
    • Berlin
      • Belfast, Berlin, Germany
    • Hessen
      • Frankfurt, Hessen, Germany
      • Giessen, Hessen, Germany
  • Ireland
      • Cork, Ireland
      • Dublin, Ireland
  • Italy
      • Genova, Italy
      • Palermo, Italy
      • Roma, Italy
      • Torino, Italy
      • Verona, Italy
  • Netherlands
      • Den Haag, Netherlands
      • Groningen, Netherlands
      • Nijmegen, Netherlands
      • Rotterdam, Netherlands
      • Utrecht, Netherlands
  • Spain
      • Barcelona, Spain
      • Madrid, Spain
      • Sevilla, Spain
      • Valencia, Spain
  • Sweden
      • Goteborg, Sweden
      • Stockholm, Sweden
      • Uppsala, Sweden
  • Switzerland
      • Bern, Switzerland
      • Zuerich, Switzerland
  • United Kingdom
      • Belfast, United Kingdom
      • London, United Kingdom
    • Devon
      • Exeter, Devon, United Kingdom
    • Lancashire
      • Liverpool, Lancashire, United Kingdom
    • South Yorkshire
      • Sheffield, South Yorkshire, United Kingdom
    • Tyne & Wear
      • Newcastle Upon Tyne, Tyne & Wear, United Kingdom
    • West Midlands
      • Birmingham, West Midlands, United Kingdom
  • United States
    • Arkansas
      • Little Rock, Arkansas, United States
    • California
      • Long Beach, California, United States
    • Colorado
      • Denver, Colorado, United States
    • Florida
      • Orlando, Florida, United States
      • Tampa, Florida, United States
    • Illinois
      • Chicago, Illinois, United States
      • Peoria, Illinois, United States
    • Massachusetts
      • Boston, Massachusetts, United States
    • Minnesota
      • Minneapolis, Minnesota, United States
    • Missouri
      • Saint Louis, Missouri, United States
    • New Hampshire
      • Manchester, New Hampshire, United States
    • New Jersey
      • Long Branch, New Jersey, United States
    • New Mexico
      • Albuquerque, New Mexico, United States
    • New York
      • Albany, New York, United States
      • Buffalo, New York, United States
      • New Hyde Park, New York, United States
      • Rochester, New York, United States
      • Syracuse, New York, United States
    • Ohio
      • Akron, Ohio, United States
      • Columbus, Ohio, United States
    • Oklahoma
      • Oklahoma City, Oklahoma, United States
    • South Carolina
      • Charleston, South Carolina, United States
    • South Dakota
      • Sioux Falls, South Dakota, United States
    • Texas
      • Fort Worth, Texas, United States
      • Tyler, Texas, United States
    • Washington
      • Seattle, Washington, United States
    • Wisconsin
      • Milwaukee, Wisconsin, United States

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

Inclusion Criteria:

  • Homozygous for the F508del CFTR mutation, genotype to be confirmed at the Screening Visit
  • Confirmed diagnosis of CF defined as a sweat chloride value ≥60 mmol/L by quantitative pilocarpine iontophoresis
  • Forced expiratory volume at one second (FEV1) ≥40% and ≤90% of predicted normal for age, sex, and height during screening
  • Stable CF disease as judged by the investigator
  • Willing to remain on a stable CF medication regimen through Week 24 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 participant.
  • An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 28 days before Day 1 (first dose of study drug)
  • Pregnant or nursing females (females of childbearing potential must have a negative pregnancy test at Screening and Day 1)
  • Sexually active participants of reproductive potential who are not willing to follow the contraception requirements

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
Placebo matched to VX-661 plus IVA FDC tablet administered orally in the morning and placebo matched to IVA tablet administered orally in the evening up to Week 24.
Drug: VX-661 Plus Ivacaftor Combination Placebo
FDC tablet, oral use
Drug: Ivacaftor placebo
Tablet, oral use
Experimental: VX-661/IVA
VX-661 100 mg plus IVA 150 mg FDC tablet administered orally in the morning and IVA 150 mg tablet administered orally in the evening up to Week 24.
Drug: Ivacaftor
Tablet, oral use
Drug: VX-661 Plus Ivacaftor Combination
FDC tablet, oral use

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 From Baseline (Day 1) in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 24
Time Frame: Day 1, Through Week 24
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Day 1, Through Week 24

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
Relative Change From Baseline (Day 1) in ppFEV1 Through Week 24
Time Frame: Day 1, Through Week 24
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Day 1, Through Week 24
Number of Pulmonary Exacerbations Per Year
Time Frame: Day 1 through Week 24
Pulmonary exacerbation was defined as a new event or change in antibiotic therapy for greater than or equal to 4 sinopulmonary signs/symptoms. Pulmonary exacerbation events per year (48 weeks) were reported.
Day 1 through Week 24
Absolute Change From Baseline (Day 1) Body Mass Index (BMI) at Week 24
Time Frame: Day 1, Week 24
BMI was defined as weight in kilograms (kg) divided by height in square meter (m^2).
Day 1, Week 24
Absolute Change From Baseline (Day 1) in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 24
Time Frame: Day 1, 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.
Day 1, Through Week 24
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Day 1 up to Week 28
AE: any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Any AE that increased in severity or newly developed at or after initial dosing of study drug to Week 28 was considered treatment-emergent.
Day 1 up to Week 28
Number of Participants With at Least One Pulmonary Exacerbation Pulmonary Exacerbation Through Week 24
Time Frame: Day 1 through Week 24
Pulmonary exacerbation was defined as a new event or change in antibiotic therapy for greater than or equal to 4 sinopulmonary signs/symptoms. Time to event data was not collected and instead, Number of Subjects with first event were collected and are reported. Time-to-first pulmonary exacerbation was planned to be estimated using Kaplan-Meier (KM) estimates. However, due to less than 50% of events, time-to-first event data was not estimated. Instead, number of participants with at least one pulmonary exacerbation event were collected and are reported.
Day 1 through Week 24
Absolute Change From Baseline (Day 1) in Sweat Chloride Through Week 24
Time Frame: Day 1, Through Week 24
Sweat samples were collected using an approved collection device.
Day 1, Through Week 24
Absolute Change From Baseline (Day 1) in BMI Z-score at Week 24 in Participants Less Than (<) 20 Years Old at the Time of Screening)
Time Frame: Day 1, 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 (BMI z-score).
Day 1, Week 24
Absolute Change From Baseline (Day 1) in Body Weight at Week 24
Time Frame: Day 1, Week 24
Day 1, Week 24
Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1 VX-661 and M2-VX-661), Ivacaftor (IVA) and IVA Metabolite (M1-IVA)
Time Frame: Pre-morning dose on Week 16
This outcome was not planned to be assessed in Placebo arm.
Pre-morning dose on Week 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

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.
January 1, 2015

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.
January 20, 2017

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.
January 20, 2017

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).
January 12, 2015

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.
January 21, 2015

First Posted (Estimate)

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.
January 27, 2015

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.
June 12, 2018

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.
May 8, 2018

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.
May 1, 2018

More Information

Terms related to this study

Keywords

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.
  • VX14-661-106

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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