Cystic FibrosisPhase 3NCT03537651
A Study to Evaluate the Safety and Efficacy of Long-term Treatment With TEZ/IVA in CF Participants With an F508del CFTR Mutation
A Phase 3 study testing TEZ/IVA and IVA in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 55 sites in 11 countries.
Trial summary
This study evaluates the long-term safety and tolerability of tezacaftor in combination with ivacaftor (TEZ/IVA) in participants with cystic fibrosis (CF) aged 6 years and older, homozygous or heterozygous for the F508del mutation. Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- TEZ/IVA and IVA
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- 55 sitesin 11 countries
- Study dates
- 25 Apr 2018to 29 Sep 2023
- 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 6 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Completed the Week 24 Visit in Study 113 Part B or the Week 8 Visit in Study 115
- Eligible CFTR Mutation
Who cannot join
- Pregnant and nursing females
- History of poor compliance with study drug and/or procedures in a previous study as deemed by the investigator
- Ongoing participation in another study with investigational drug
- Other protocol defined Inclusion/Exclusion criteria may apply.
Trial locations and contacts
55 sites in 11 countries.
55 sites in 11 countries
United States28 sites
Providence Alaska Medical Center
Anchorage, Alaska, 99508
Center for Advanced Pediatrics
Atlanta, Georgia, 30329
Children's Hospital Colorado
Aurora, Colorado, 80045
Austin Children's Chest Associates
Austin, Texas, 78723
University of Alabama at Birmingham
Birmingham, Alabama, 35233
St. Luke's CF Center of Idaho
Boise, Idaho, 83702
Boston Children's Hospital
Boston, Massachusetts, 02115
UBMD Pediatrics/ CF Center of Western New York
Buffalo, New York, 14203
Medical University of South Carolina (MUSC)
Charleston, South Carolina, 29425
Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Cook Children's Medical Center
Fort Worth, Texas, 76104
Baylor College of Medicine
Houston, Texas, 77030
Riley Hospital for Children Indiana University Health
Indianapolis, Indiana, 46202
The Children's Mercy Hospital
Kansas City, Missouri, 64108
Arkansas Children's Hospital
Little Rock, Arkansas, 72202
Children's Hospital Los Angeles
Los Angeles, California, 90027
Dartmouth Hitchcock Medical Center
Manchester, New Hampshire, 03756
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Children's Hospital & Clinics of Minnesota
Minneapolis, Minnesota, 55404
Columbia University Medical Center
New York, New York, 10032
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Seattle Children's Hospital
Seattle, Washington, 98105
Sanford Children's Speciality Clinic
Sioux Falls, South Dakota, 57105
Johns Hopkins All Children's Hospital Outpatient Care Center
St. Petersburg, Florida, 33701
SUNY Upstate Medical University
Syracuse, New York, 13202
Nemours/ Alfred I. duPont Hospital for Children
Wilmington, Delaware, 19803
Wake Forest Baptist Health
Winston-Salem, North Carolina, 27157
Germany7 sites
Universitaetsklinkum Koeln, CF-Studienzentrum
Cologne
Universitätsklinikum Essen
Essen
Clinic of J.W. Goethe University
Frankfurt
Justus-Leibig-Universitat Zentrum fur Kinderheilkunde und Jugendmedizin
Giessen
Medizinische Hochschule Hannover
Hanover
Universitaetsklinikum Jena, Mukoviszidose-Zentrum
Jena
Universitaetsklinikum Tuebingen Klinik fuer Kinder- und Jugendmedizin
Tübingen
Australia4 sites
Perth Children's Hospital
Nedlands
John Hunter Hospital & Hunter Medical Research Institute and John Hunter Children's Hospital
New Lambton
Lady Cilento Children's Hospital
South Brisbane
The Children's Hospital at Westmead
Westmead
Canada3 sites
McGill University Health Centre, Glen Site, Montreal Children's Hospital
Montreal, Quebec
The Hospital for Sick Children
Toronto, Ontario
British Columbia's Children's Hospital
Vancouver, British Columbia
United Kingdom3 sites
Leeds General Infirmary
Leeds
Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital
London
Southampton General Hospital
Southampton
Belgium2 sites
Universitair Ziekenhuis Brussel - Campus Jette
Brussels
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
Leuven
France2 sites
Groupe Hospitaler Pellegrin, CHU De Bordeaux
Bordeaux
Hopital Necker, Enfants Malades
Paris
Ireland2 sites
Our Lady's Children's Hospital
Dublin
University Hospital Limerick
Limerick
Switzerland2 sites
Inselspital - Universitaetsspital Bern
Bern
Kinderspital Zuerich
Zurich
Poland1 site
Klinika Mukowiscydozy IMD Oddozial Chorob Pluc Szpzoz IM. Dzieci WarszaWY
Łomianki
About this study
Official title: A Phase 3, Open-label, Rollover Study to Evaluate the Safety and Efficacy of Long-term Treatment With Tezacaftor in Combination With Ivacaftor in Subjects With Cystic Fibrosis Aged 6 Years and Older, Homozygous or Heterozygous for the F508del-CFTR Mutation
This study evaluates the long-term safety and tolerability of tezacaftor in combination with ivacaftor (TEZ/IVA) in participants with cystic fibrosis (CF) aged 6 years and older, homozygous or heterozygous for the F508del mutation.
- Conditions
- Cystic Fibrosis
- Being tested
- TEZ/IVA, IVA
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TEZ/IVADrug
Also called VX-661/VX-770, tezacaftor/ivacaftor
Fixed-dose combination tablet for oral administration.
IVADrug
Also called VX-770, ivacaftor
Tablet for oral administration.
| Study group | Role | What they receive |
|---|---|---|
| TEZ/IVA | Experimental | Part A: Participants weighing less than (<)40 kilograms (kg) at Day 1 received tezacaftor (TEZ) 50 milligrams (mg) once daily (qd)/ivacaftor (IVA) 75 mg every 12 hours (q12h) and the participants weighing greater than or equals to (>=) 40 kg at Day 1 received TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 96 weeks. Doses were adjusted upward for changes in body weight and/or age.
Part B: Participants weighing <30 kg at Day 1 received TEZ 50 mg qd/IVA 75 mg q12h and the participants weighing >=30 kg at Day 1 received TEZ 100 mg qd/IVA 150 mg q12h in the treatment period up to 192 weeks. Doses were adjusted upward for changes in body weight and/or age. Receives: Drug: TEZ/IVA; Drug: IVA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Measured: Day 1 up to Week 100
Secondary outcomes (9)
Part A: Absolute Change in Lung Clearance Index2.5 (LCI2.5) for 115/116 FAS (TEZ/IVA Group)
The LCI2.5 index is the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting values and is calculated by dividing the sum of exhaled tidal breaths (cumulative exhaled volume (CEV)) by simultaneously measured functional residual capacity (FRC). An LCI of 7.5 and below is normal; values greater than 7.5 are abnormal. LCI is able to detect abnormalities in lung function earlier than more traditional modalities such as spirometry.
Measured: From Parent Study 115 Baseline at Week 96 (Study 116)
Part A: Absolute Change in LCI2.5 for 113B/116 LCI FAS
The LCI2.5 index is the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting values and is calculated by dividing the sum of exhaled tidal breaths (cumulative exhaled volume (CEV)) by simultaneously measured functional residual capacity (FRC). An LCI of 7.5 and below is normal; values greater than 7.5 are abnormal. LCI is able to detect abnormalities in lung function earlier than more traditional modalities such as spirometry.
Measured: From Parent Study 113B Baseline at Week 96 (Study 116)
Part A: Absolute Change in Sweat Chloride (SwCl) for 115/116 FAS (TEZ/IVA Group)
Sweat samples were collected using an approved collection device.
Measured: From Parent Study 115 Baseline at Week 96 (Study 116)
Part A: Absolute Change in SwCl for 113B/116 FAS
Sweat samples were collected using an approved collection device.
Measured: From Parent Study 113B Baseline at Week 96 (Study 116)
Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 115/116 FAS (TEZ/IVA Group)
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with CF. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Measured: From Parent Study 115 Baseline at Week 96 (Study 116)
Part A: Absolute Change in CFQ-R Respiratory Domain Score for 113B/116 FAS
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with CF. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Measured: From Parent Study 113B Baseline at Week 96 (Study 116)
Part A: Absolute Change in Body Mass Index (BMI) for 115/116 FAS (TEZ/IVA Group)
BMI was defined as weight in kilograms (kg) divided by squared height in meters (m^2).
Measured: From Parent Study 115 Baseline at Week 96 (Study 116)
Part A: Absolute Change in BMI for 113B/116 FAS
BMI was defined as weight in kg divided by m^2.
Measured: From Parent Study 113B Baseline at Week 96 (Study 116)
Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measured: Day 1 up to Week 192
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2018
- Study start25 Apr 2018
- Primary completion28 Oct 2020
- Study completion29 Sep 2023
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 (3)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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 130 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
- NCT03537651
- Sponsor's protocol ID
- VX17-661-116
- Other IDs
- 2017-002968-40, 2017
- Status last verified
- Mar 2024
- First submitted
- 15 May 2018
- Last updated
- 19 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
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 37983082Sawicki GS, Chilvers M, McNamara J, Naehrlich L, Saunders C, Sermet-Gaudelus I, Wainwright CE, Ahluwalia N, Campbell D, Harris RS, Paz-Diaz H, Shih JL, Davies JC. A Phase 3, open-label, 96-week trial to study the safety, tolerability, and efficacy of tezacaftor/ivacaftor in children >/= 6 years of age homozygous for F508del or heterozygous for F508del and a residual function CFTR variant. J Cyst Fibros. 2022 Jul;21(4):675-683. doi: 10.1016/j.jcf.2022.02.003. Epub 2022 Feb 18.
PubMed 35190292Southern 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 33331662
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Open-label, Rollover Study to Evaluate the Safety and Efficacy of Long-term Treatment With Tezacaftor in Combination With Ivacaftor in Subjects With Cystic Fibrosis Aged 6 Years and Older, Homozygous or Heterozygous for the F508del-CFTR Mutation
- ClinicalTrials.gov ID
- NCT03537651
- Acronym / sponsor ID
- VX17-661-116
- Conditions
- Cystic Fibrosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 130 participants (actual)
- Lead sponsor
- Vertex Pharmaceuticals IncorporatedIndustry (pharma, biotech, devices)
- Study start
- 25 Apr 2018 (actual)
- Primary completion
- 28 Oct 2020 (actual)
- Study completion
- 29 Sep 2023 (actual)
- First posted
- 25 May 2018 (actual)
- Results
- Posted 26 Nov 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the long-term safety and tolerability of tezacaftor in combination with ivacaftor (TEZ/IVA) in participants with cystic fibrosis (CF) aged 6 years and older, homozygous or heterozygous for the F508del mutation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TEZ/IVA | Experimental | Drug: TEZ/IVA, Drug: IVAPart A: Participants weighing less than (<)40 kilograms (kg) at Day 1 received tezacaftor (TEZ) 50 milligrams (mg) once daily (qd)/ivacaftor (IVA) 75 mg every 12 hours (q12h) and the participants weighing greater than or equals to (>=) 40 kg at Day 1 received TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 96 weeks. Doses were adjusted upward for changes in body weight and/or age. Part B: Participants weighing <30 kg at Day 1 received TEZ 50 mg qd/IVA 75 mg q12h and the participants weighing >=30 kg at Day 1 received TEZ 100 mg qd/IVA 150 mg q12h in the treatment period up to 192 weeks. Doses were adjusted upward for changes in body weight and/or age. |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Completed the Week 24 Visit in Study 113 Part B or the Week 8 Visit in Study 115
- Eligible CFTR Mutation
Key exclusion criteria (4 listed)
- Pregnant and nursing females
- History of poor compliance with study drug and/or procedures in a previous study as deemed by the investigator
- Ongoing participation in another study with investigational drug
- 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 |
|---|---|---|
| TEZ/IVAAlso: VX-661/VX-770, tezacaftor/ivacaftorFixed-dose combination tablet for oral administration. | Drug | TEZ/IVA |
| IVAAlso: VX-770, ivacaftorTablet for oral administration. | Drug | TEZ/IVA |
Primary outcome
Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: Day 1 up to Week 100
9 secondary outcomes
Part A: Absolute Change in Lung Clearance Index2.5 (LCI2.5) for 115/116 FAS (TEZ/IVA Group)
Time frame: From Parent Study 115 Baseline at Week 96 (Study 116)
Part A: Absolute Change in LCI2.5 for 113B/116 LCI FAS
Time frame: From Parent Study 113B Baseline at Week 96 (Study 116)
Part A: Absolute Change in Sweat Chloride (SwCl) for 115/116 FAS (TEZ/IVA Group)
Time frame: From Parent Study 115 Baseline at Week 96 (Study 116)
Part A: Absolute Change in SwCl for 113B/116 FAS
Time frame: From Parent Study 113B Baseline at Week 96 (Study 116)
Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 115/116 FAS (TEZ/IVA Group)
Time frame: From Parent Study 115 Baseline at Week 96 (Study 116)
Part A: Absolute Change in CFQ-R Respiratory Domain Score for 113B/116 FAS
Time frame: From Parent Study 113B Baseline at Week 96 (Study 116)
Part A: Absolute Change in Body Mass Index (BMI) for 115/116 FAS (TEZ/IVA Group)
Time frame: From Parent Study 115 Baseline at Week 96 (Study 116)
Part A: Absolute Change in BMI for 113B/116 FAS
Time frame: From Parent Study 113B Baseline at Week 96 (Study 116)
Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Day 1 up to Week 192
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2024.
- 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 35190292Sawicki GS, Chilvers M, McNamara J, Naehrlich L, Saunders C, Sermet-Gaudelus I, Wainwright CE, Ahluwalia N, Campbell D, Harris RS, Paz-Diaz H, Shih JL, Davies JC. A Phase 3, open-label, 96-week trial to study the safety, tolerability, and efficacy of tezacaftor/ivacaftor in children >/= 6 years of age homozygous for F508del or heterozygous for F508del and a residual function CFTR variant. J Cyst Fibros. 2022 Jul;21(4):675-683. doi: 10.1016/j.jcf.2022.02.003. Epub 2022 Feb 18.
- 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.
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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.
55 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 TEZ/IVA and IVA in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 55 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 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 19 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 55 sites in United States, Germany, Australia, Canada, United Kingdom 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. 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 26 Nov 2021). 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?
Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) (time frame: Day 1 up to Week 100). 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 NCT03537651, which also lists 3 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 19 Apr 2024.