Cystic FibrosisPhase 3NCT03460990
A Study of VX-659 Combination Therapy in CF Subjects Homozygous for F508del (F/F)
A Phase 3 study testing VX-659/TEZ/IVA, TEZ/IVA and IVA in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 46 sites in 6 countries.
Trial summary
This study will evaluate the efficacy of VX-659 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are homozygous for the F508del mutation (F/F). 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-659/TEZ/IVA, TEZ/IVA and IVA
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 116 participants
- Where
- 46 sitesin 6 countries
- Study dates
- 1 May 2018to 8 Oct 2018
- 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 mutation (F/F)
- Forced expiratory volume in 1 second (FEV1) value ≥40% and ≤90% of predicted mean for age, sex, and height
Who cannot join
- Clinically significant cirrhosis with or without portal hypertension
- Lung infection with organisms associated with a more rapid decline in pulmonary status
- Solid organ or hematological transplantation
- Other protocol defined Inclusion/Exclusion criteria may apply
Trial locations and contacts
46 sites in 6 countries.
46 sites in 6 countries
United States28 sites
Albany Medical College
Albany, New York, 12208
The Johns Hopkins Hospital
Baltimore, Maryland, 21287
University of Alabama at Birmingham
Birmingham, Alabama, 35233
St. Luke's CF Center of Idaho
Boise, Idaho, 83712
Boston Children's Hospital
Boston, Massachusetts, 02115
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Helen DeVos Children's Hospital CF Center
Grand Rapids, Michigan, 49503
Baylor College of Medicine
Houston, Texas, 77030
Indiana Clinical Research Center, IU Health University Hospital
Indianapolis, Indiana, 46202
The University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
Children's Mercy Hospital
Kansas City, Missouri, 64108
University of Tennessee Medical Center-Adult Cystic Fibrosis Clinic
Knoxville, Tennessee, 37920
Children's Foundation Research Center/ Le Bonheur Children's Hospital
Memphis, Tennessee, 38103
University of Miami/Miller School of Medicine
Miami, Florida, 33136
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Rutgers-Robert Wood Johnson Medical School
New Brunswick, New Jersey, 08901
Yale New Haven Medical Center
New Haven, Connecticut, 06511
Northwell Health, Long Island Jewish Medical Center
New Hyde Park, New York, 11040
Columbia University Medical Center
New York, New York, 10032
Advocate Children's Hospital- Park Ridge/ North Suburban Pulmonary and Critical Care Consultants
Niles, Illinois, 60714
Respiratory Diseases of Children and Adolescents
Oklahoma City, Oklahoma, 73211
Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15224
Oregon Health & Science University
Portland, Oregon, 97239
University of Utah/ Primary Children's Medical Center
Salt Lake City, Utah, 84132
Seattle Children's Hospital
Seattle, Washington, 98105
Sanford Research/ USD
Sioux Falls, South Dakota, 57105
Washington University School of Medicine / St. Louis Children's Hospital
St Louis, Missouri, 63110
SUNY Upstate Medical University
Syracuse, New York, 13210
Australia5 sites
Royal Adelaide Hospital
Adelaide
Prince Charles Hospital
Chermside
The Alfred Hospital
Melbourne, Victoria
Institute for Respiratory Health Inc./ Sir Charles Gairdner Hospital
Nedlands
John Hunter Hospital & Hunter Medical Research Institute
New Lambton Heights
United Kingdom5 sites
Papworth Hospital NHS Foundation Trust, Papworth Everard
Cambridge
Liverpool Heart and Chest Hospital
Liverpool
Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital
London
Wythenshawe Hospital
Manchester
University Hospital Llandough
Penarth
Ireland3 sites
Cork University Hospital
Dublin
Our Lady's Children's Hospital
Dublin
St. Vincent's University Hospital
Dublin
Spain3 sites
Hospital Universitari Vall d Hebron
Barcelona
Hospital Universitari Vall d'Hebron Servicio de Broncoscopia
Barcelona
Hospital Universitario Virgen del Rocio
Seville
Germany2 sites
Charite Paediatric Pulmonology Department
Berlin
Pneumologische Praxis Pasing
München
About this study
Official title: A Phase 3, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-659 Combination Therapy in Subjects With Cystic Fibrosis Who Are Homozygous for the F508del Mutation (F/F)
This study will evaluate the efficacy of VX-659 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are homozygous for the F508del mutation (F/F).
- Conditions
- Cystic Fibrosis
- Being tested
- VX-659/TEZ/IVA, TEZ/IVA, IVA, Placebo
- 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-659/TEZ/IVADrug
Also called VX-659/VX-661/VX-770, VX-659/tezacaftor/ivacaftor
Participants received VX-659/TEZ/IVA orally once daily in the morning.
TEZ/IVADrug
Also called VX-661/VX-770, tezacaftor/ivacaftor
Participants received TEZ/IVA orally once daily in the morning.
IVADrug
Also called VX-770, ivacaftor
Participants received IVA orally once daily in the evening.
PlaceboDrug
Participants received placebo matched TEZ/IVA orally once daily in the morning.
PlaceboDrug
Participants received placebo matched to VX-659/TEZ/IVA orally once daily in the morning.
| Study group | Role | What they receive |
|---|---|---|
| TEZ/IVA | Active comparator | Following a run-in period of 4 weeks with Tezacaftor (TEZ)/Ivacaftor (IVA), participants received TEZ 100 milligram (mg)/IVA 150 mg as fixed-dose combination (FDC) tablet in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the triple combination (TC) treatment period. Receives: Drug: TEZ/IVA; Drug: IVA; Drug: Placebo |
| VX-659/TEZ/IVA TC | Experimental | Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-659 240 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period. Receives: Drug: VX-659/TEZ/IVA; Drug: IVA; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Measured: From Baseline at Week 4
Secondary outcomes (4)
Absolute Change in Sweat Chloride (SwCl)
Sweat samples were collected using an approved collection device.
Measured: From Baseline at Week 4
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
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: From Baseline at Week 4
Safety and Tolerability as Assessed Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measured: From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)
Observed Pre-Dose Concentration (Ctrough) of VX-659, TEZ, TEZ Metabolite (M1-TEZ), and IVA
Measured: From Day 1 and Week 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2018
- Study start1 May 2018
- Primary completion26 Sep 2018
- Study completion8 Oct 2018
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.
- 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
- 116 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
- NCT03460990
- Sponsor's protocol ID
- VX17-659-103
- Other IDs
- 2017-004133-82, 2017
- Status last verified
- Sep 2019
- First submitted
- 1 Mar 2018
- Last updated
- 17 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-659 Combination Therapy in Subjects With Cystic Fibrosis Who Are Homozygous for the F508del Mutation (F/F)
- ClinicalTrials.gov ID
- NCT03460990
- Acronym / sponsor ID
- VX17-659-103
- Conditions
- Cystic Fibrosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 116 participants (actual)
- Lead sponsor
- Vertex Pharmaceuticals IncorporatedIndustry (pharma, biotech, devices)
- Study start
- 1 May 2018 (actual)
- Primary completion
- 26 Sep 2018 (actual)
- Study completion
- 8 Oct 2018 (actual)
- First posted
- 9 Mar 2018 (actual)
- Results
- Posted 17 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the efficacy of VX-659 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are homozygous for the F508del mutation (F/F).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TEZ/IVA | Active comparator | Drug: TEZ/IVA, Drug: IVA, Drug: PlaceboFollowing a run-in period of 4 weeks with Tezacaftor (TEZ)/Ivacaftor (IVA), participants received TEZ 100 milligram (mg)/IVA 150 mg as fixed-dose combination (FDC) tablet in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the triple combination (TC) treatment period. |
| VX-659/TEZ/IVA TC | Experimental | Drug: VX-659/TEZ/IVA, Drug: IVA, Drug: PlaceboFollowing a run-in period of 4 weeks with TEZ/IVA, participants received VX-659 240 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Homozygous for the F508del mutation (F/F)
- Forced expiratory volume in 1 second (FEV1) value ≥40% and ≤90% of predicted mean for age, sex, and height
Key exclusion criteria (4 listed)
- Clinically significant cirrhosis with or without portal hypertension
- Lung infection with organisms associated with a more rapid decline in pulmonary status
- Solid organ or hematological transplantation
- Other protocol defined Inclusion/Exclusion criteria may apply
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-659/TEZ/IVAAlso: VX-659/VX-661/VX-770, VX-659/tezacaftor/ivacaftorParticipants received VX-659/TEZ/IVA orally once daily in the morning. | Drug | VX-659/TEZ/IVA TC |
| TEZ/IVAAlso: VX-661/VX-770, tezacaftor/ivacaftorParticipants received TEZ/IVA orally once daily in the morning. | Drug | TEZ/IVA |
| IVAAlso: VX-770, ivacaftorParticipants received IVA orally once daily in the evening. | Drug | TEZ/IVA, VX-659/TEZ/IVA TC |
| PlaceboParticipants received placebo matched TEZ/IVA orally once daily in the morning. | Drug | VX-659/TEZ/IVA TC |
| PlaceboParticipants received placebo matched to VX-659/TEZ/IVA orally once daily in the morning. | Drug | TEZ/IVA |
Primary outcome
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Time frame: From Baseline at Week 4
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
4 secondary outcomes
Absolute Change in Sweat Chloride (SwCl)
Time frame: From Baseline at Week 4
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
Time frame: From Baseline at Week 4
Safety and Tolerability as Assessed Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)
Observed Pre-Dose Concentration (Ctrough) of VX-659, TEZ, TEZ Metabolite (M1-TEZ), and IVA
Time frame: From Day 1 and Week 4
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
46 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing VX-659/TEZ/IVA, TEZ/IVA and IVA in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 46 sites in 6 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 2 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 17 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 46 sites in United States, Australia, United Kingdom, Ireland, Spain and 1 more country. 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 17 Oct 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 in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) (time frame: From Baseline at Week 4). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Oct 2019.