Cystic FibrosisPhase 3NCT02392234
A Phase 3 Study to Evaluate the Efficacy and Safety of Ivacaftor and VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Mutation
A Phase 3 study testing VX-661/Ivacaftor and Ivacaftor in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 93 sites in 11 countries.
Trial summary
The purpose of this study is to evaluate the efficacy and safety of VX-661 in combination with ivacaftor (IVA, VX-770) and IVA monotherapy in participants with Cystic Fibrosis (CF) who are heterozygous for F508del-CFTR allele and a second allele with a CFTR mutation predicted to have residual function. 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/Ivacaftor and Ivacaftor
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 248 participants
- Where
- 93 sitesin 11 countries
- Study dates
- Mar 2015to Feb 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
- Heterozygous for F508del-CFTR and a second allele with a CFTR mutation predicted to have residual function
- Forced Expiratory Volume in 1 Second (FEV1) greater than or equal to (≥) 40 percent (%) and less than or equal to (≤) 90% of predicted normal for age, sex, and height during screening
- Sweat chloride value ≥60 millimole per liter (mmol/L) during screening OR as documented in the participant's medical record
- Stable CF disease as judged by the investigator
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
- History of solid organ or hematological transplantation
- Ongoing or prior participation in an investigational drug study (including studies investigating VX-661, lumacaftor [VX-809], and/or ivacaftor) within 30 days of screening
- Pregnant and nursing females
- Sexually active participants of reproductive potential who are not willing to follow the contraception requirements
Trial locations and contacts
93 sites in 11 countries.
93 sites in 11 countries
United States47 sites
Study site
Akron, Ohio
Study site
Ann Arbor, Michigan
Study site
Atlanta, Georgia
Study site
Aurora, Colorado
Study site
Austin, Texas
Study site
Baltimore, Maryland
Study site
Birmingham, Alabama
Study site
Boston, Massachusetts
Study site
Chapel Hill, North Carolina
Study site
Charleston, South Carolina
Study site
Chicago, Illinois
Study site
Cincinnati, Ohio
Study site
Cleveland, Ohio
Study site
Dallas, Texas
Study site
Denver, Colorado
Study site
Gainesville, Florida
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Grand Rapids, Michigan
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Iowa City, Iowa
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Lebanon, New Hampshire
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Long Beach, California
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Memphis, Tennessee
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Miami, Florida
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Milwaukee, Wisconsin
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Minneapolis, Minnesota
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New York, New York
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Norfolk, Virginia
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Oakland, California
Study site
Orlando, Florida
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Palo Alto, California
Study site
Park Ridge, Illinois
Study site
Pensacola, Florida
Study site
Philadelphia, Pennsylvania
Study site
Phoenix, Arizona
Study site
Pittsburgh, Pennsylvania
Study site
Portland, Oregon
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Sacramento, California
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Salt Lake City, Utah
Study site
Seattle, Washington
Study site
Sioux Falls, South Dakota
Study site
Spokane, Washington
Study site
St Louis, Missouri
Study site
Syracuse, New York
Study site
Tampa, Florida
Study site
Toledo, Ohio
Study site
Tucson, Arizona
Study site
Tyler, Texas
Study site
Valhalla, New York
France7 sites
Study site
Bordeaux
Study site
Bron, Rhone
Study site
Lille, Nord
Study site
Marseille, Bouches-du-Rhone
Study site
Montpellier, Herault
Study site
Paris, Paris
Study site
Rennes, Ille Et Vilaine
United Kingdom7 sites
Study site
Exeter, Devon
Study site
Glasgow, Strathclyde
Study site
Leeds, West Yorkshire
Study site
Liverpool, Lancashire
Study site
London, Greater London
Study site
Manchester, Greater Manchester
Study site
Southampton, Hampshire
Germany6 sites
Study site
Berlin
Study site
Essen, North Rhine-Westphalia
Study site
Hanover, Lower Saxony
Study site
Jena, Thuringia
Study site
München, Bavaria
Study site
Munich, Bavaria
Italy6 sites
Study site
Ancona
Study site
Milan
Study site
Orbassano
Study site
Potenza
Study site
Roma
Study site
Verona
Australia4 sites
Study site
Adelaide
Study site
Melbourne
Study site
South Brisbane
Study site
Westmead
Canada4 sites
Study site
Montreal
Study site
Québec
Study site
Toronto
Study site
Vancouver
Israel4 sites
Study site
Haifa
Study site
Jerusalem
Study site
Petah Tikva
Study site
Ramat Gan
Netherlands4 sites
Study site
Amsterdam
Study site
Rotterdam
Study site
The Hague
Study site
Utrecht
Switzerland3 sites
Study site
Bern
Study site
Sankt Gallen
Study site
Zurich
About this study
Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Efficacy and Safety of Ivacaftor and VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-CFTR Mutation, and a Second Allele With a CFTR Mutation Predicted to Have Residual Function
The purpose of this study is to evaluate the efficacy and safety of VX-661 in combination with ivacaftor (IVA, VX-770) and IVA monotherapy in participants with Cystic Fibrosis (CF) who are heterozygous for F508del-CFTR allele and a second allele with a CFTR mutation predicted to have residual function.
- Conditions
- Cystic Fibrosis
- Being tested
- VX-661/Ivacaftor, Ivacaftor, Placebo matched to VX-661/ ivacaftor, Placebo matched to Ivacaftor
- 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/IvacaftorDrug
Also called VX-661+VX-770
Fixed dose combination tablet, oral use
IvacaftorDrug
Also called IVA, VX-770
Tablet, oral use
Placebo matched to VX-661/ ivacaftorDrug
Fixed dose combination tablet, oral use
Placebo matched to IvacaftorDrug
Tablet, oral use
| Study group | Role | What they receive |
|---|---|---|
| VX-661/Ivacaftor combination | Experimental | Not described Receives: Drug: VX-661/Ivacaftor; Drug: Ivacaftor; Drug: Placebo matched to Ivacaftor |
| Ivacaftor monotherapy | Experimental | Not described Receives: Drug: Ivacaftor; Drug: Placebo matched to VX-661/ ivacaftor |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo matched to VX-661/ ivacaftor; Drug: Placebo matched to Ivacaftor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Average of Week 4 and Week 8
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Measured: Baseline, Week 4 and Week 8 of each treatment period
Secondary outcomes (6)
Absolute Change From Study Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Average of Week 4 and Week 8
The CFQ-R assessed respiratory symptoms on a scale with scores ranging from 0 to 100; where higher scores indicated fewer symptoms and better health-related quality of life.
Measured: Baseline, Week 4 and Week 8 of each treatment period
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measured: Day 1 up to Week 28
Relative Change From Study Baseline in ppFEV1 at Average of Week 4 and Week 8
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Measured: Baseline, Week 4 and Week 8 of each treatment period
Absolute Change From Study Baseline in Sweat Chloride at Average of Week 4 and Week 8
Measured: Baseline, Week 4 and Week 8 of each treatment period
Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1 VX-661), IVA and IVA Metabolite (M1 IVA) After Administration of VX-661/IVA Combination Therapy
Measured: Pre-morning dose on Week 8 of each treatment period
Ctrough of IVA and IVA Metabolite (M1 IVA) After Administration of IVA Monotherapy
Measured: Pre-morning dose on Week 8 of each treatment period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2015 (estimated)
- Study startMar 2015
- Primary completionFeb 2017
- Study completionFeb 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by Vertex Pharmaceuticals IncorporatedThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 248 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vertex Pharmaceuticals Incorporated
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02392234
- Sponsor's protocol ID
- VX14-661-108
- Other IDs
- 2014-004788-18, 2014
- Status last verified
- May 2018
- First submitted
- 12 Mar 2015
- Last updated
- 12 Jun 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Heneghan M, Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2023 Nov 20;11(11):CD010966. doi: 10.1002/14651858.CD010966.pub4.
PubMed 37983082Acaster 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 36509366Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.
PubMed 33331662Rowe SM, Daines C, Ringshausen FC, Kerem E, Wilson J, Tullis E, Nair N, Simard C, Han L, Ingenito EP, McKee C, Lekstrom-Himes J, Davies JC. Tezacaftor-Ivacaftor in Residual-Function Heterozygotes with Cystic Fibrosis. N Engl J Med. 2017 Nov 23;377(21):2024-2035. doi: 10.1056/NEJMoa1709847. Epub 2017 Nov 3.
PubMed 29099333
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Efficacy and Safety of Ivacaftor and VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-CFTR Mutation, and a Second Allele With a CFTR Mutation Predicted to Have Residual Function
- ClinicalTrials.gov ID
- NCT02392234
- Acronym / sponsor ID
- VX14-661-108
- Conditions
- Cystic Fibrosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 248 participants (actual)
- Lead sponsor
- Vertex Pharmaceuticals IncorporatedIndustry (pharma, biotech, devices)
- Study start
- Mar 2015
- Primary completion
- Feb 2017 (actual)
- Study completion
- Feb 2017 (actual)
- First posted
- 18 Mar 2015 (estimated)
- Results
- Posted 12 Jun 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the efficacy and safety of VX-661 in combination with ivacaftor (IVA, VX-770) and IVA monotherapy in participants with Cystic Fibrosis (CF) who are heterozygous for F508del-CFTR allele and a second allele with a CFTR mutation predicted to have residual function.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| VX-661/Ivacaftor combination | Experimental | Drug: VX-661/Ivacaftor, Drug: Ivacaftor, Drug: Placebo matched to Ivacaftor |
| Ivacaftor monotherapy | Experimental | Drug: Ivacaftor, Drug: Placebo matched to VX-661/ ivacaftor |
| Placebo | Placebo comparator | Drug: Placebo matched to VX-661/ ivacaftor, Drug: Placebo matched to Ivacaftor |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Heterozygous for F508del-CFTR and a second allele with a CFTR mutation predicted to have residual function
- Forced Expiratory Volume in 1 Second (FEV1) greater than or equal to (≥) 40 percent (%) and less than or equal to (≤) 90% of predicted normal for age, sex, and height during screening
- Sweat chloride value ≥60 millimole per liter (mmol/L) during screening OR as documented in the participant's medical record
- Stable CF disease as judged by the investigator
Key exclusion criteria (6 listed)
- 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
- History of solid organ or hematological transplantation
- Ongoing or prior participation in an investigational drug study (including studies investigating VX-661, lumacaftor [VX-809], and/or ivacaftor) within 30 days of screening
- Pregnant and nursing females
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VX-661/IvacaftorAlso: VX-661+VX-770Fixed dose combination tablet, oral use | Drug | VX-661/Ivacaftor combination |
| IvacaftorAlso: IVA, VX-770Tablet, oral use | Drug | Ivacaftor monotherapy, VX-661/Ivacaftor combination |
| Placebo matched to VX-661/ ivacaftorFixed dose combination tablet, oral use | Drug | Ivacaftor monotherapy, Placebo |
| Placebo matched to IvacaftorTablet, oral use | Drug | Placebo, VX-661/Ivacaftor combination |
Primary outcome
Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Average of Week 4 and Week 8
Time frame: Baseline, Week 4 and Week 8 of each treatment period
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
6 secondary outcomes
Absolute Change From Study Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Average of Week 4 and Week 8
Time frame: Baseline, Week 4 and Week 8 of each treatment period
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Day 1 up to Week 28
Relative Change From Study Baseline in ppFEV1 at Average of Week 4 and Week 8
Time frame: Baseline, Week 4 and Week 8 of each treatment period
Absolute Change From Study Baseline in Sweat Chloride at Average of Week 4 and Week 8
Time frame: Baseline, Week 4 and Week 8 of each treatment period
Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1 VX-661), IVA and IVA Metabolite (M1 IVA) After Administration of VX-661/IVA Combination Therapy
Time frame: Pre-morning dose on Week 8 of each treatment period
Ctrough of IVA and IVA Metabolite (M1 IVA) After Administration of IVA Monotherapy
Time frame: Pre-morning dose on Week 8 of each treatment period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37983082Heneghan M, Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2023 Nov 20;11(11):CD010966. doi: 10.1002/14651858.CD010966.pub4.
- Derived from this study: PubMed 36509366Acaster 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.
- Derived from this study: PubMed 33331662Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.
- Derived from this study: PubMed 29099333Rowe SM, Daines C, Ringshausen FC, Kerem E, Wilson J, Tullis E, Nair N, Simard C, Han L, Ingenito EP, McKee C, Lekstrom-Himes J, Davies JC. Tezacaftor-Ivacaftor in Residual-Function Heterozygotes with Cystic Fibrosis. N Engl J Med. 2017 Nov 23;377(21):2024-2035. doi: 10.1056/NEJMoa1709847. Epub 2017 Nov 3.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
93 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing VX-661/Ivacaftor and Ivacaftor in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 93 sites in 11 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 4 inclusion and 6 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 93 sites in United States, France, United Kingdom, Germany, Italy and 6 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 Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Average of Week 4 and Week 8 (time frame: Baseline, Week 4 and Week 8 of each treatment period). 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 NCT02392234, which also lists 4 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; AzTrials last refreshed its copy on 29 Oct 2026.