Cystic FibrosisPhase 2NCT02951182
A Study Evaluating the Safety and Efficacy of VX-440 Combination Therapy in Subjects With Cystic Fibrosis
A Phase 2 study testing TEZ, IVA and VX-440 in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 40 sites in 10 countries.
Trial summary
This is a Phase 2, randomized, double-blind, placebo- and active-controlled, parallel group, multicenter study to evaluate the safety, tolerability, and efficacy of VX-440 in dual and triple combination with tezacaftor (TEZ; VX-661) and ivacaftor (IVA; VX-770) in subjects with cystic fibrosis (CF) who are homozygous… 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?
- TEZ, IVA and VX-440
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 74 participants
- Where
- 40 sitesin 10 countries
- Study dates
- Oct 2016to Aug 2017
- Phase
- Phase 2
- 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
- Willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.
- To prevent pregnancy, female participants of childbearing potential and their male partners will be required to use pre-specified, highly effective methods of non-hormonal contraception. Male participants with female partners of childbearing potential will be required to use a condom.
- Body weight ≥35 kg.
- Sweat chloride value ≥60 mmol/L from test results obtained during screening.
- Subjects must have an eligible CFTR genotype:
- Heterozygous for F508del and a minimal function (MF) mutation known or predicted not to be responsive to TEZ and/or IVA.
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- Homozygous for F508del
- Subjects must have an FEV1 ≥40% and ≤90% of predicted normal for age, sex, and height at the Screening Visit
- Stable CF disease as judged by the investigator.
- Willing to remain on a stable CF medication regimen through the planned end of treatment 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 subject.
- History of cirrhosis with portal hypertension.
- Risk factors for Torsade de Pointes
- History of hemolysis.
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency assessed at Screening.
- Clinically significant abnormal laboratory values at screening
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- An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 28 days before the first dose of study drug.
- Lung infection with organisms associated with a more rapid decline in pulmonary status
- An acute illness not related to CF within 14 days before the first dose of study drug
- A standard digital ECG demonstrating QTc >450 msec at screening.
- History of solid organ or hematological transplantation.
- History or evidence of cataract or lens opacity determined to be clinically significant by the ophthalmologist or optometrist based on the ophthalmologic examination during the Screening Period.
- History of alcohol or drug abuse in the past year, including but not limited to, cannabis, cocaine, and opiates, as deemed by the investigator.
- Ongoing or prior participation in an investigational drug study, with certain exceptions. (e.g., ongoing participation in NCT02565914)
- Use of commercially available CFTR modulator (e.g., Kalydeco, Orkambi) within 14 days before screening (applies only to the Heterozygous F508del/MF cohorts; does not apply to the Homozygous F508del/F508del Cohort).
- Pregnant or nursing females: Females of childbearing potential must have a negative pregnancy test at screening and Day 1.
Trial locations and contacts
40 sites in 10 countries.
40 sites in 10 countries
United States22 sites
The Johns Hopkins Hospital
Baltimore, Maryland
St. Luke's CF Center of Idaho
Boise, Idaho
Boston Children's Hospital
Boston, Massachusetts
Massachusetts General Hospital Cystic Fibrosis Center
Boston, Massachusetts
Nationwide Children's Hospital
Columbus, Ohio
The University of Texas Southwestern Center
Dallas, Texas
National Jewish Health
Denver, Colorado
Cystic Fibrosis Center of Chicago
Glenview, Illinois
New York Medical College
Hawthorne, New York
Joe Di Maggio Cystic Fibrosis & Pulmonary Center
Hollywood, Florida
University of Minnesota
Minneapolis, Minnesota
Long Island Jewish Medical Center
New Hyde Park, New York
Columbia University Medical Center
New York, New York
Children's Hospital of the Kings Daughters
Norfolk, Virginia
Respiratory Diseases of Children and Adolescents
Oklahoma City, Oklahoma
Central Florida Pulmonary Group
Orlando, Florida
Stanford University
Palo Alto, California
UPMC OSPARS Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania
University of California
San Francisco, California
Seattle Children's Hospital
Seattle, Washington
Sanford Children's Specialty Clinic Sanford Research USD
Sioux Falls, South Dakota
The Arizona Board of Regents on behalf of the University of Arizona
Tucson, Arizona
Australia3 sites
Royal Adelaide Hospital
Adelaide
Prince Charles Hospital
Chermside
John Hunter Hospital & Hunter Medical Research Institute
New Lambton Heights
Germany3 sites
University Hospital Cologne
Cologne
Mukeviszidose-Zentrum am Universtitatsklinikum Jena
Jena
Pneumologische Praxis Pasing
München
United Kingdom3 sites
Heart of England NHS Foundation Trust
Birmingham
Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital
London
Southampton University Hospitals NHS Foundation Trust
Southampton
Belgium2 sites
Universitair Ziekenhuis Brussel
Brussels
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
Leuven
Canada2 sites
St. Michael's Hospital
Toronto, Ontario
St. Paul's Hopsital
Vancouver, British Columbia
Spain2 sites
Hospital Universitari Vall d´Hebron Servicio de Broncoscopia
Barcelona
Hospital Universitario Virgen del Rocio
Seville
About this study
Official title: A Phase 2, Randomized, Double-blind, Controlled Study to Evaluate the Safety and Efficacy of VX-440 Combination Therapy in Subjects Aged 12 Years and Older With Cystic Fibrosis
This is a Phase 2, randomized, double-blind, placebo- and active-controlled, parallel group, multicenter study to evaluate the safety, tolerability, and efficacy of VX-440 in dual and triple combination with tezacaftor (TEZ; VX-661) and ivacaftor (IVA; VX-770) in subjects with cystic fibrosis (CF) who are homozygous for the F508del mutation of the CF transmembrane conductance regulator (CFTR) gene (F508del/F508del), or who are heterozygous for the F508del mutation and a minimal function (MF) CFTR mutation not likely to respond to TEZ and/or IVA therapy (F508del/MF).
- Conditions
- Cystic Fibrosis
- Being tested
- TEZ, IVA, VX-440, Matched 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.
TEZDrug
Also called tezacaftor, VX-661
IVADrug
Also called ivacaftor, VX-770
VX-440Drug
Matched PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Placebo - Cohort 1A and 1B Combined | Placebo comparator | Participants received placebo matched to VX-440/TEZ/IVA as triple combination for 4 weeks. Receives: Drug: Matched Placebo |
| Part 1 Cohort 1A: Triple Combination (TC) | Experimental | Participants received VX-440 200 milligram (mg) every 12 hours (q12h)/TEZ 100 mg once daily (qd)/IVA 150 mg q12h as triple combination for 4 weeks. Receives: Drug: TEZ; Drug: IVA; Drug: VX-440 |
| Part 1 Cohort 1B: TC Low Dose | Experimental | Participants received VX-440 200 mg q12h/TEZ 50 mg q12h/IVA 150 mg q12h as triple combination for 4 weeks. Receives: Drug: TEZ; Drug: IVA; Drug: VX-440 |
| Part 1 Cohort 1B: TC High Dose | Experimental | Participants received VX-440 600 mg q12h/TEZ 50 mg q12h/IVA 300 mg q12h as triple combination for 4 weeks. Receives: Drug: TEZ; Drug: IVA; Drug: VX-440 |
| Part 2: TEZ/IVA | Active comparator | Following a 4-week run-in period on TEZ 100 mg qd/IVA150 mg q12h, participants received placebo matched to VX-440 and TEZ 50 mg q12h/IVA 300 mg q12h for 4 weeks in treatment period and TEZ 100 mg qd/IVA150 mg q12h for 4 weeks in washout period. Receives: Drug: TEZ; Drug: IVA; Drug: Matched Placebo |
| Part 2: TC-2 | Experimental | Following a 4-week run-in period on TEZ 100 mg qd/IVA150 mg q12h, participants received VX-440 600 mg q12h/ TEZ 50 mg q12h/IVA 300 mg q12h for 4 weeks for 4 weeks in treatment period and TEZ 100 mg qd/IVA150 mg q12h for 4 weeks in washout period. Receives: Drug: TEZ; Drug: IVA; Drug: VX-440 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measured: From first dose of Study Drug in the Treatment Period through Safety Follow-up Visit (Up to Day 57 for Part 1 and Day 85 for Part 2)
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 through Day 29
Secondary outcomes (4)
Absolute Change in Sweat Chloride Concentrations
Sweat samples were collected using an approved collection device.
Measured: From Baseline through Day 29
Relative Change in ppFEV1
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Measured: From Baseline through Day 29
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 Day 29
Pre-dose Plasma Concentration (Ctrough) of VX-440, TEZ, M1-TEZ, IVA and M1-IVA
Measured: Predose at Day 8, Day 15 and Day 29
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2016 (estimated)
- Study startOct 2016
- Primary completionAug 2017
- Study completionAug 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.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 74 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
- NCT02951182
- Sponsor's protocol ID
- VX15-440-101
- Other IDs
- 2016-000454-36, 2016
- Status last verified
- Aug 2020
- First submitted
- 26 Oct 2016
- Last updated
- 28 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Double-blind, Controlled Study to Evaluate the Safety and Efficacy of VX-440 Combination Therapy in Subjects Aged 12 Years and Older With Cystic Fibrosis
- ClinicalTrials.gov ID
- NCT02951182
- Acronym / sponsor ID
- VX15-440-101
- Conditions
- Cystic Fibrosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- Vertex Pharmaceuticals IncorporatedIndustry (pharma, biotech, devices)
- Study start
- Oct 2016 (actual)
- Primary completion
- Aug 2017 (actual)
- Study completion
- Aug 2017 (actual)
- First posted
- 1 Nov 2016 (estimated)
- Results
- Posted 28 Aug 2020
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 2, randomized, double-blind, placebo- and active-controlled, parallel group, multicenter study to evaluate the safety, tolerability, and efficacy of VX-440 in dual and triple combination with tezacaftor (TEZ; VX-661) and ivacaftor (IVA; VX-770) in subjects with cystic fibrosis (CF) who are homozygous for the F508del mutation of the CF transmembrane conductance regulator (CFTR) gene (F508del/F508del), or who are heterozygous for the F508del mutation and a minimal function (MF) CFTR mutation not likely to respond to TEZ and/or IVA therapy (F508del/MF).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Part 1: Placebo - Cohort 1A and 1B Combined | Placebo comparator | Drug: Matched PlaceboParticipants received placebo matched to VX-440/TEZ/IVA as triple combination for 4 weeks. |
| Part 1 Cohort 1A: Triple Combination (TC) | Experimental | Drug: TEZ, Drug: IVA, Drug: VX-440Participants received VX-440 200 milligram (mg) every 12 hours (q12h)/TEZ 100 mg once daily (qd)/IVA 150 mg q12h as triple combination for 4 weeks. |
| Part 1 Cohort 1B: TC Low Dose | Experimental | Drug: TEZ, Drug: IVA, Drug: VX-440Participants received VX-440 200 mg q12h/TEZ 50 mg q12h/IVA 150 mg q12h as triple combination for 4 weeks. |
| Part 1 Cohort 1B: TC High Dose | Experimental | Drug: TEZ, Drug: IVA, Drug: VX-440Participants received VX-440 600 mg q12h/TEZ 50 mg q12h/IVA 300 mg q12h as triple combination for 4 weeks. |
| Part 2: TEZ/IVA | Active comparator | Drug: TEZ, Drug: IVA, Drug: Matched PlaceboFollowing a 4-week run-in period on TEZ 100 mg qd/IVA150 mg q12h, participants received placebo matched to VX-440 and TEZ 50 mg q12h/IVA 300 mg q12h for 4 weeks in treatment period and TEZ 100 mg qd/IVA150 mg q12h for 4 weeks in washout period. |
| Part 2: TC-2 | Experimental | Drug: TEZ, Drug: IVA, Drug: VX-440Following a 4-week run-in period on TEZ 100 mg qd/IVA150 mg q12h, participants received VX-440 600 mg q12h/ TEZ 50 mg q12h/IVA 300 mg q12h for 4 weeks for 4 weeks in treatment period and TEZ 100 mg qd/IVA150 mg q12h for 4 weeks in washout period. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.
- To prevent pregnancy, female participants of childbearing potential and their male partners will be required to use pre-specified, highly effective methods of non-hormonal contraception. Male participants with female partners of childbearing potential will be required to use a condom.
- Body weight ≥35 kg.
- Sweat chloride value ≥60 mmol/L from test results obtained during screening.
- Subjects must have an eligible CFTR genotype:
Key exclusion criteria (16 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.
- History of cirrhosis with portal hypertension.
- Risk factors for Torsade de Pointes
- History of hemolysis.
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency assessed at Screening.
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 |
|---|---|---|
| TEZAlso: tezacaftor, VX-661 | Drug | Part 1 Cohort 1A: Triple Combination (TC), Part 1 Cohort 1B: TC High Dose, Part 1 Cohort 1B: TC Low Dose, Part 2: TC-2, Part 2: TEZ/IVA |
| IVAAlso: ivacaftor, VX-770 | Drug | Part 1 Cohort 1A: Triple Combination (TC), Part 1 Cohort 1B: TC High Dose, Part 1 Cohort 1B: TC Low Dose, Part 2: TC-2, Part 2: TEZ/IVA |
| VX-440 | Drug | Part 1 Cohort 1A: Triple Combination (TC), Part 1 Cohort 1B: TC High Dose, Part 1 Cohort 1B: TC Low Dose, Part 2: TC-2 |
| Matched Placebo | Drug | Part 1: Placebo - Cohort 1A and 1B Combined, Part 2: TEZ/IVA |
Primary outcome
Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From first dose of Study Drug in the Treatment Period through Safety Follow-up Visit (Up to Day 57 for Part 1 and Day 85 for Part 2)
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Time frame: From Baseline through Day 29
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 Concentrations
Time frame: From Baseline through Day 29
Relative Change in ppFEV1
Time frame: From Baseline through Day 29
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
Time frame: From Baseline at Day 29
Pre-dose Plasma Concentration (Ctrough) of VX-440, TEZ, M1-TEZ, IVA and M1-IVA
Time frame: Predose at Day 8, Day 15 and Day 29
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2020.
- 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.
40 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TEZ, IVA and VX-440 in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 40 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 10 inclusion and 16 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 28 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 40 sites in United States, Australia, Germany, United Kingdom, 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 28 Aug 2020). 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?
Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) (time frame: From first dose of Study Drug in the Treatment Period through Safety Follow-up Visit (Up to Day 57 for Part 1 and Day 85 for Part 2)). The study lists 2 primary outcomes in all. 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 28 Aug 2020.