Cystic FibrosisPhase 3NCT02412111
A Phase 3 Study of Tezacaftor (VX-661) in Combination With Ivacaftor (VX-770) in Subjects Aged 12 Years and Older With Cystic Fibrosis (CF), Who Have One F508del-CFTR Mutation and a Second Mutation That Has Been Demonstrated to be Clinically Responsive to Ivacaftor
A Phase 3 study testing Ivacaftor and Tezacaftor/Ivacaftor in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 68 sites in 10 countries.
Trial summary
This is a Phase 3, randomized, double-blind, ivacaftor-controlled, parallel-group, multicenter study of tezacaftor in combination with ivacaftor in subjects aged 12 years and older with CF who are heterozygous for the F508del-CFTR mutation and a second CFTR allele with a gating defect that is clinically demonstrated… 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?
- Ivacaftor and Tezacaftor/Ivacaftor
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 156 participants
- Where
- 68 sitesin 10 countries
- Study dates
- Jun 2015to Sep 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 mutation and a second CFTR allele with a gating defect that is clinically demonstrated to be ivacaftor responsive
- FEV1 ≥40% and ≤90% of predicted normal for age, sex, and height during screening
- 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 subject.
- Pregnant and nursing females (females of childbearing potential must have a negative pregnancy test at Screening and Week -4 Visits).
- Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements
Trial locations and contacts
68 sites in 10 countries.
68 sites in 10 countries
United States33 sites
Study site
Albany, New York
Study site
Ann Arbor, Michigan
Study site
Augusta, Georgia
Study site
Aurora, Colorado
Study site
Birmingham, Alabama
Study site
Boston, Massachusetts
Study site
Charleston, South Carolina
Study site
Cincinnati, Ohio
Study site
Detroit, Michigan
Study site
Grand Rapids, Michigan
Study site
Houston, Texas
Study site
Indianapolis, Indiana
Study site
Knoxville, Tennessee
Study site
Lebanon, New Hampshire
Study site
Lexington, Kentucky
Study site
Manchester, New Hampshire
Study site
Morgantown, West Virginia
Study site
Morristown, New Jersey
Study site
Nashville, Tennessee
Study site
New Brunswick, New Jersey
Study site
New York, New York
Study site
Oakland, California
Study site
Oklahoma City, Oklahoma
Study site
Omaha, Nebraska
Study site
Orlando, Florida
Study site
Philadelphia, Pennsylvania
Study site
Pittsburgh, Pennsylvania
Study site
Portland, Oregon
Study site
Salt Lake City, Utah
Study site
San Diego, California
Study site
St Louis, Missouri
Study site
Toledo, Ohio
Study site
Washington D.C., District of Columbia
United Kingdom9 sites
Study site
Belfast
Study site
Birmingham
Study site
Cardiff
Study site
Glasgow
Study site
Leeds
Study site
London
Study site
Manchester
Study site
Newcastle
Study site
Southampton
Germany8 sites
Study site
Dresden
Study site
Erlangen
Study site
Essen
Study site
Frankfurt
Study site
Giessen
Study site
Heidelberg
Study site
Jena
Study site
München
Australia5 sites
Study site
Chermside
Study site
Clayton
Study site
Melbourne
Study site
South Brisbane
Study site
Westmead
About this study
Official title: A Phase 3, Randomized, Double-Blind, Ivacaftor-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, Heterozygous for the F508del-CFTR Mutation and a Second CFTR Allele With a Gating Defect That Is Clinically Demonstrated to be Ivacaftor Responsive
This is a Phase 3, randomized, double-blind, ivacaftor-controlled, parallel-group, multicenter study of tezacaftor in combination with ivacaftor in subjects aged 12 years and older with CF who are heterozygous for the F508del-CFTR mutation and a second CFTR allele with a gating defect that is clinically demonstrated to be ivacaftor responsive.
- Conditions
- Cystic Fibrosis
- Being tested
- Ivacaftor, Tezacaftor/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.
IvacaftorDrug
Also called VX-770
Tezacaftor/IvacaftorDrug
Also called VX-661/VX-770
| Study group | Role | What they receive |
|---|---|---|
| Ivacaftor (Run-in Period) | Experimental | Ivacaftor 150 milligram (mg) tablet orally every 12 hours for 4 weeks. Receives: Drug: Ivacaftor |
| VX-661 + Ivacaftor (Active comparator period) | Experimental | VX-661 100 mg and ivacaftor 150 mg fixed-dose combination tablet orally once daily in the morning and ivacaftor 150 mg tablet orally once daily in the evening for 8 weeks. Receives: Drug: Ivacaftor; Drug: Tezacaftor/Ivacaftor |
| Ivacaftor monotherapy (Active comparator period) | Active comparator | Ivacaftor 150 mg tablet orally every 12 hours as monotherapy for 8 weeks. Receives: Drug: Ivacaftor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Measured: Baseline, Through Week 8
Secondary outcomes (5)
Relative Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Measured: Baseline, Through Week 8
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline Through Week 8
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: Baseline, Through Week 8
Absolute Change From Baseline in Sweat Chloride Through Week 8
Sweat samples were collected using an approved collection device.
Measured: Baseline, Through Week 8
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measured: Baseline up to Week 16
Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1-VX-661), Ivacaftor (IVA) and IVA Metabolite (M1-IVA)
Measured: Predose on Week -2 for Run-in period; Pre-dose on Week 2 for Active comparator period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2015 (estimated)
- Study startJun 2015
- Primary completionSep 2017
- Study completionSep 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 (1)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
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 156 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
- NCT02412111
- Sponsor's protocol ID
- VX14-661-109
- Status last verified
- Jan 2019
- First submitted
- 3 Apr 2015
- Last updated
- 8 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
McKone EF, DiMango EA, Sutharsan S, Barto TL, Campbell D, Ahluwalia N, Higgins M, Owen CA, Tullis E. A phase 3, randomized, double-blind, parallel-group study to evaluate tezacaftor/ivacaftor in people with cystic fibrosis heterozygous for F508del-CFTR and a gating mutation. J Cyst Fibros. 2021 Mar;20(2):234-242. doi: 10.1016/j.jcf.2020.11.003. Epub 2020 Dec 16.
PubMed 33339768
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomized, Double-Blind, Ivacaftor-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, Heterozygous for the F508del-CFTR Mutation and a Second CFTR Allele With a Gating Defect That Is Clinically Demonstrated to be Ivacaftor Responsive
- ClinicalTrials.gov ID
- NCT02412111
- Acronym / sponsor ID
- VX14-661-109
- Conditions
- Cystic Fibrosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 156 participants (actual)
- Lead sponsor
- Vertex Pharmaceuticals IncorporatedIndustry (pharma, biotech, devices)
- Study start
- Jun 2015 (actual)
- Primary completion
- Sep 2017 (actual)
- Study completion
- Sep 2017 (actual)
- First posted
- 8 Apr 2015 (estimated)
- Results
- Posted 8 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 3, randomized, double-blind, ivacaftor-controlled, parallel-group, multicenter study of tezacaftor in combination with ivacaftor in subjects aged 12 years and older with CF who are heterozygous for the F508del-CFTR mutation and a second CFTR allele with a gating defect that is clinically demonstrated to be ivacaftor responsive.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Ivacaftor (Run-in Period) | Experimental | Drug: IvacaftorIvacaftor 150 milligram (mg) tablet orally every 12 hours for 4 weeks. |
| VX-661 + Ivacaftor (Active comparator period) | Experimental | Drug: Ivacaftor, Drug: Tezacaftor/IvacaftorVX-661 100 mg and ivacaftor 150 mg fixed-dose combination tablet orally once daily in the morning and ivacaftor 150 mg tablet orally once daily in the evening for 8 weeks. |
| Ivacaftor monotherapy (Active comparator period) | Active comparator | Drug: IvacaftorIvacaftor 150 mg tablet orally every 12 hours as monotherapy for 8 weeks. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Heterozygous for F508del-CFTR mutation and a second CFTR allele with a gating defect that is clinically demonstrated to be ivacaftor responsive
- FEV1 ≥40% and ≤90% of predicted normal for age, sex, and height during screening
- Stable CF disease as judged by the investigator.
Key exclusion criteria (3 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 subject.
- Pregnant and nursing females (females of childbearing potential must have a negative pregnancy test at Screening and Week -4 Visits).
- Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements
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 |
|---|---|---|
| IvacaftorAlso: VX-770 | Drug | Ivacaftor (Run-in Period), Ivacaftor monotherapy (Active comparator period), VX-661 + Ivacaftor (Active comparator period) |
| Tezacaftor/IvacaftorAlso: VX-661/VX-770 | Drug | VX-661 + Ivacaftor (Active comparator period) |
Primary outcome
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8
Time frame: Baseline, Through Week 8
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
5 secondary outcomes
Relative Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8
Time frame: Baseline, Through Week 8
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline Through Week 8
Time frame: Baseline, Through Week 8
Absolute Change From Baseline in Sweat Chloride Through Week 8
Time frame: Baseline, Through Week 8
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Baseline up to Week 16
Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1-VX-661), Ivacaftor (IVA) and IVA Metabolite (M1-IVA)
Time frame: Predose on Week -2 for Run-in period; Pre-dose on Week 2 for Active comparator period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33339768McKone EF, DiMango EA, Sutharsan S, Barto TL, Campbell D, Ahluwalia N, Higgins M, Owen CA, Tullis E. A phase 3, randomized, double-blind, parallel-group study to evaluate tezacaftor/ivacaftor in people with cystic fibrosis heterozygous for F508del-CFTR and a gating mutation. J Cyst Fibros. 2021 Mar;20(2):234-242. doi: 10.1016/j.jcf.2020.11.003. Epub 2020 Dec 16.
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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.
68 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ivacaftor and Tezacaftor/Ivacaftor in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 68 sites in 10 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 3 inclusion and 3 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 8 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 68 sites in United States, United Kingdom, Germany, Australia, Belgium and 5 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. 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 8 Jan 2019). 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 in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8 (time frame: Baseline, Through Week 8). 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 NCT02412111, which also lists 1 linked publication.
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 8 Jan 2019.