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Cystic FibrosisPhase 3NCT02347657

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

A Phase 3 study testing VX-661 Plus Ivacaftor Combination and Ivacaftor in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 74 sites in 12 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
Cystic Fibrosis
What is being tested?
VX-661 Plus Ivacaftor Combination and Ivacaftor
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
510 participants
Where
74 sitesin 12 countries
Study dates
Jan 2015to 20 Jan 2017
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

74 sites in 12 countries.

74 sites in 12 countries

United States27 sites
  • Study site

    Akron, Ohio

  • Study site

    Albany, New York

  • Study site

    Albuquerque, New Mexico

  • Study site

    Boston, Massachusetts

  • Study site

    Buffalo, New York

  • Study site

    Charleston, South Carolina

  • Study site

    Chicago, Illinois

  • Study site

    Columbus, Ohio

  • Study site

    Denver, Colorado

  • Study site

    Fort Worth, Texas

  • Study site

    Little Rock, Arkansas

  • Study site

    Long Beach, California

  • Study site

    Long Branch, New Jersey

  • Study site

    Manchester, New Hampshire

  • Study site

    Milwaukee, Wisconsin

  • Study site

    Minneapolis, Minnesota

  • Study site

    New Hyde Park, New York

  • Study site

    Oklahoma City, Oklahoma

  • Study site

    Orlando, Florida

  • Study site

    Peoria, Illinois

  • Study site

    Rochester, New York

  • Study site

    Seattle, Washington

  • Study site

    Sioux Falls, South Dakota

  • Study site

    St Louis, Missouri

  • Study site

    Syracuse, New York

  • Study site

    Tampa, Florida

  • Study site

    Tyler, Texas

Other trials in United States

Germany7 sites
  • Study site

    Belfast, State of Berlin

  • Study site

    Berlin

  • Study site

    Frankfurt am Main, Hesse

  • Study site

    Giessen, Hesse

  • Study site

    Heidelberg, Baden-Wurttemberg

  • Study site

    Munich, Bavaria

  • Study site

    Würzburg, Bavaria

Other trials in Germany

United Kingdom7 sites
  • Study site

    Belfast

  • Study site

    Birmingham, West Midlands

  • Study site

    Exeter, Devon

  • Study site

    Liverpool, Lancashire

  • Study site

    London

  • Study site

    Newcastle upon Tyne, Tyne & Wear

  • Study site

    Sheffield, South Yorkshire

Other trials in United Kingdom

France6 sites
  • Study site

    Bordeaux, Girande

  • Study site

    Lille, Nord

  • Study site

    Marseille, Bouches-du-Rhone

  • Study site

    Paris, Paris

  • Study site

    Pierre-Bénite, Rhone

  • Study site

    Roscoff, Finistere

Other trials in France

Canada5 sites
  • Study site

    Calgary, Alberta

  • Study site

    Halifax, Nova Scotia

  • Study site

    Montreal, Quebec

  • Study site

    Toronto, Ontario

  • Study site

    Vancouver, British Columbia

Other trials in Canada

Italy5 sites
  • Study site

    Genova

  • Study site

    Palermo

  • Study site

    Roma

  • Study site

    Torino

  • Study site

    Verona

Other trials in Italy

Netherlands5 sites
  • Study site

    Groningen

  • Study site

    Nijmegen

  • Study site

    Rotterdam

  • Study site

    The Hague

  • Study site

    Utrecht

Other trials in Netherlands

Spain4 sites
  • Study site

    Barcelona

  • Study site

    Madrid

  • Study site

    Seville

  • Study site

    Valencia

Other trials in Spain

Sweden3 sites
  • Study site

    Gothenburg

  • Study site

    Stockholm

  • Study site

    Uppsala

Other trials in Sweden

Ireland2 sites
  • Study site

    Cork

  • Study site

    Dublin

Other trials in Ireland

Switzerland2 sites
  • Study site

    Bern

  • Study site

    Zurich

Other trials in Switzerland

Denmark1 site
  • Study site

    Copenhagen O

Other trials in Denmark

About this study

Official title: 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.

Read the 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.

Conditions
Cystic Fibrosis
Being tested
VX-661 Plus Ivacaftor Combination, Ivacaftor, VX-661 Plus Ivacaftor Combination Placebo, Ivacaftor placebo
Keywords
Homozygous for the F508del CFTR Mutation
Medical subject headings
Cystic Fibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VX-661 Plus Ivacaftor CombinationDrug

    FDC tablet, oral use

  • IvacaftorDrug

    Tablet, oral use

  • VX-661 Plus Ivacaftor Combination PlaceboDrug

    FDC tablet, oral use

  • Ivacaftor placeboDrug

    Tablet, oral use

Study groups in NCT02347657
Study groupRoleWhat they receive
PlaceboPlacebo comparatorPlacebo 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.
Receives: Drug: VX-661 Plus Ivacaftor Combination Placebo; Drug: Ivacaftor placebo
VX-661/IVAExperimentalVX-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.
Receives: Drug: VX-661 Plus Ivacaftor Combination; Drug: Ivacaftor

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Absolute Change From Baseline (Day 1) in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 24

    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

    Measured: Day 1, Through Week 24

Secondary outcomes (10)
  1. Relative Change From Baseline (Day 1) in ppFEV1 Through Week 24

    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

    Measured: Day 1, Through Week 24

  2. Number of Pulmonary Exacerbations Per Year

    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.

    Measured: Day 1 through Week 24

  3. Absolute Change From Baseline (Day 1) Body Mass Index (BMI) at Week 24

    BMI was defined as weight in kilograms (kg) divided by height in square meter (m^2).

    Measured: Day 1, Week 24

  4. Absolute Change From Baseline (Day 1) in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score 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.

    Measured: Day 1, Through Week 24

  5. Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

    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.

    Measured: Day 1 up to Week 28

  6. Number of Participants With at Least One Pulmonary Exacerbation Pulmonary Exacerbation 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.

    Measured: Day 1 through Week 24

  7. Absolute Change From Baseline (Day 1) in Sweat Chloride Through Week 24

    Sweat samples were collected using an approved collection device.

    Measured: Day 1, Through Week 24

  8. 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)

    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).

    Measured: Day 1, Week 24

  9. Absolute Change From Baseline (Day 1) in Body Weight at Week 24

    Measured: Day 1, Week 24

  10. Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1 VX-661 and M2-VX-661), Ivacaftor (IVA) and IVA Metabolite (M1-IVA)

    This outcome was not planned to be assessed in Placebo arm.

    Measured: Pre-morning dose on Week 16

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2015 (estimated)
  2. Study startJan 2015
  3. Primary completion20 Jan 2017
  4. Study completion20 Jan 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
510 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02347657
Sponsor's protocol ID
VX14-661-106
Status last verified
May 2018
First submitted
12 Jan 2015
Last updated
12 Jun 2018
Data monitoring committee
Yes
Expanded access
Available

Publications

  • Acaster S, Mukuria C, Rowen D, Brazier JE, Wainwright CE, Quon BS, Duckers J, Quittner AL, Lou Y, Sosnay PR, McGarry LJ. Development of the Cystic Fibrosis Questionnaire-Revised-8 Dimensions: Estimating Utilities From the Cystic Fibrosis Questionnaire-Revised. Value Health. 2023 Apr;26(4):567-578. doi: 10.1016/j.jval.2022.12.002. Epub 2022 Dec 9.

    PubMed 36509366
  • Taylor-Cousar JL, Munck A, McKone EF, van der Ent CK, Moeller A, Simard C, Wang LT, Ingenito EP, McKee C, Lu Y, Lekstrom-Himes J, Elborn JS. Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del. N Engl J Med. 2017 Nov 23;377(21):2013-2023. doi: 10.1056/NEJMoa1709846. Epub 2017 Nov 3.

    PubMed 29099344

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing VX-661 Plus Ivacaftor Combination and Ivacaftor in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 74 sites in 12 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 74 sites in United States, Germany, United Kingdom, France, Canada and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Jun 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02347657, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2018.

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