Cystic FibrosisPhase 3NCT03150719
A Study to Evaluate Safety, Efficacy, and Tolerability of TEZ/IVA in Orkambi® (Lumacaftor/Ivacaftor) -Experienced Subjects With Cystic Fibrosis (CF)
A Phase 3 study testing Tezacaftor/Ivacaftor and Ivacaftor in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 53 sites in 3 countries.
Trial summary
Study VX16-661-114 (Study 114) is a Phase 3b, randomized, double-blind, placebo-controlled, parallel-group, multicenter study in subjects aged 12 years and older with CF who are homozygous for the F508del mutation on the cystic fibrosis transmembrane conductance regulator gene (CFTR) gene and who discontinued… 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?
- Tezacaftor/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
- 98 participants
- Where
- 53 sitesin 3 countries
- Study dates
- 24 May 2017to 9 Aug 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
- Willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.
- Prior discontinuation of Orkambi, with at least 1 respiratory sign or symptom considered related to therapy.
- Resolution or stabilization of qualifying event(s) >28 days prior to Screening.
- Discontinuation of Orkambi therapy must have occurred within approximately 12 weeks from the first dose of Orkambi.
- Homozygous for F508del mutation in the CFTR gene as documented in the subject's medical record. If genotype documentation is not available in the medical record, genotyping will be performed during screening.
- FEV1 ≥25% and ≤90% of predicted normal for age, sex, and height.
- Stable CF disease as judged by the investigator.
- Other protocol defined inclusion criteria could apply.
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.
- Recent rapid or progressive deterioration in respiratory status.
- Receiving continuous oxygen at >2L/min or on face-mask ventilation.
- Any protocol-defined exclusionary laboratory values at Screening.
- Child-Pugh Class B or C hepatic impairment.
- An acute upper or lower respiratory infection, pulmonary exacerbation, or change in therapy for pulmonary disease within 28 days before Day 1.
Show all 13Show fewer
- Documentation of colonization with organisms associated with a more rapid decline in pulmonary status.
- History of lung transplantation since most recent initiation of Orkambi.
- History of alcohol or drug abuse in the past year as deemed by the investigator.
- Participation in an investigational drug study or use of a CFTR modulator within 28 days or 5 terminal half-lives of the investigational drug or modulator (whichever is longer).
- Use of restricted medications or foods within the specified window before the first dose of study drug, or an anticipated need or use of restricted medication or foods after the first dose of study drug.
- Pregnant or nursing females: Females of child-bearing potential must have a negative pregnancy test at Screening and Day 1.
- Other protocol defined exclusion criteria could apply.
Trial locations and contacts
53 sites in 3 countries.
53 sites in 3 countries
United States41 sites
Children's Speciality Services at North Druid Hills
Atlanta, Georgia, 30324
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723
Billings Clinic
Billings, Montana, 59101
University of Alabama at Birmingham
Birmingham, Alabama, 35233
St. Luke's CF Center of Idaho
Boise, Idaho, 83702
Massachusetts General Hospital Cystic Fibrosis Center
Boston, Massachusetts, 02114
Boston Children's Hospital
Boston, Massachusetts, 02115
Medical University of South Carolina
Charleston, South Carolina, 29425
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
National Jewish Health
Denver, Colorado, 80206
Duke University Medical Center
Durham, North Carolina, 27710
UCSF - Fresno, Community Regional Medical Center
Fresno, California, 93701
Riley Hospital for Children at Indiana University Health
Indianapolis, Indiana, 46202
The University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
University of Mississippi Medical Center
Jackson, Mississippi, 39216
University of Kansas Medical Center
Kansas City, Kansas, 66160
Children's Mercy Hospital
Kansas City, Missouri, 64108
Kentucky Clinic
Lexington, Kentucky, 40536
Miller Children's Hospital / Long Beach Memorial
Long Beach, California, 90806
Children's Hospital Los Angeles
Los Angeles, California, 90027
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
The University of Tennessee Medical Center
Nashville, Tennessee, 37920
Yale New Haven Hospital
New Haven, Connecticut, 06510
Tulane Medical Center
New Orleans, Louisiana, 70112
Mount Sinai Beth Israel
New York, New York, 10003
Advocate Children's Hospital - Park Ridge / North Suburban Pulmonary and Critical Care Consultants
Niles, Illinois, 60714
Children's Hospital of the King's Daughters
Norfolk, Virginia, 23507
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Santiago Reyes, M.D.
Oklahoma City, Oklahoma, 73112
Central Florida Pulmonary Group
Orlando, Florida, 32803
Arnold Palmer Hospital
Orlando, Florida, 32806
Drexel University College of Medicine/ Drexel Adult Cystic Fibrosis Center
Philadelphia, Pennsylvania, 19107
Phoenix Children's Hospital
Phoenix, Arizona, 85016
Children's Hospital of Richmond at VCU, Children's Pavilion
Richmond, Virginia, 23298
University of Utah / Primary Children's Medical Center
Salt Lake City, Utah, 84132
The University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78207
Rady Children's Hospital
San Diego, California, 92123
Southern Illinois University
Springfield, Illinois, 62702
Tampa General Hospital Cardiac and Lung Transplant Clinic
Tampa, Florida, 33606
New York Medical College
Valhalla, New York, 10595
Wake Forest University Baptist Medical Center
Winston-Salem, North Carolina, 27157
France7 sites
Centre Hospitalier Intercommunal de Créteil
Créteil
Centre Hospitalier Universitaire De Grenoble - Hopital Michallon
Grenoble
CHU de Montpellier - Hopital Arnaud de Villeneuve
Montpellier
Centre Hospitalier Universitaire De Nantes
Nantes
Centre hospitalier universitaire de Nice, Pulmonology
Nice
Hopital Cochin
Paris
Centre Hospitalier Universitaire - Hopitaux de Rouen
Rouen
Germany5 sites
Charite Paediatric Pulmonology Department
Berlin
Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen
Essen
Klinikum Innenstadt, University of Munich
München
Pneumologische Praxis Pasing
München
Universitaetsklinikum Tuebingen Klinik fuer Kinder- und Jugendmedizin
Tübingen
About this study
Official title: Phase 3b, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Safety, Efficacy, and Tolerability of Tezacaftor/Ivacaftor (TEZ/IVA) in an Orkambi-experienced Population Who Are Homozygous for the F508del CFTR Mutation
Study VX16-661-114 (Study 114) is a Phase 3b, randomized, double-blind, placebo-controlled, parallel-group, multicenter study in subjects aged 12 years and older with CF who are homozygous for the F508del mutation on the cystic fibrosis transmembrane conductance regulator gene (CFTR) gene and who discontinued treatment with Orkambi due to respiratory symptoms considered related to treatment. This study is designed to evaluate the safety and efficacy of Tezacaftor/Ivacaftor (TEZ/IVA).
- Conditions
- Cystic Fibrosis
- Being tested
- Tezacaftor/Ivacaftor, Ivacaftor, 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.
Tezacaftor/IvacaftorDrug
Also called TEZ/IVA; VX-661/VX-770
TEZ 100 mg/IVA 150 mg fixed-dose combination tablet.
IvacaftorDrug
Also called VX-770; IVA
IVA 150 mg tablet.
PlaceboDrug
Placebo matched to TEZ/IVA fixed-dose combination tablet.
PlaceboDrug
Placebo matched to IVA tablet.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Participants received placebo matched to TEZ/IVA fixed-dose combination tablet orally once daily in the morning followed by placebo matched to IVA tablet orally once daily in the evening for 56 days. Receives: Drug: Placebo |
| TEZ/IVA | Experimental | Participants received TEZ 100 milligram (mg)/IVA 150 mg fixed-dose combination tablet orally once daily in the morning and IVA 150 mg tablet orally once daily in the evening for 56 days. Receives: Drug: Tezacaftor/Ivacaftor; Drug: Ivacaftor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Respiratory Adverse Events of Special Interest (RAESIs)
RAESIs included chest discomfort, dyspnea (shortness of breath), respiration abnormal (chest tightness), asthma, bronchial hyperreactivity, bronchospasm, and wheezing.
Measured: Day 1 up to Day 84
Secondary outcomes (5)
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Average of Day 28 and Day 56 Measurements
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Measured: Baseline, Day 28 and Day 56
Relative Change From Baseline in ppFEV1 at Average of Day 28 and Day 56 Measurements
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Measured: Baseline, Day 28 and Day 56
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Average of Day 28 and Day 56 Measurements
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, Day 28 and Day 56
Tolerability as Assessed by Number of Participants Who Discontinued Treatment
Measured: Day 1 through Day 56
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measured: Day 1 up to Day 84
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2017
- Study start24 May 2017
- Primary completion9 Aug 2018
- Study completion9 Aug 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
- 98 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
- NCT03150719
- Sponsor's protocol ID
- VX16-661-114
- Other IDs
- 2017-000540-18, 2017
- Status last verified
- Sep 2019
- First submitted
- 3 May 2017
- Last updated
- 12 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Expanded access
- Available
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 3b, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Safety, Efficacy, and Tolerability of Tezacaftor/Ivacaftor (TEZ/IVA) in an Orkambi-experienced Population Who Are Homozygous for the F508del CFTR Mutation
- ClinicalTrials.gov ID
- NCT03150719
- Acronym / sponsor ID
- VX16-661-114
- Conditions
- Cystic Fibrosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 98 participants (actual)
- Lead sponsor
- Vertex Pharmaceuticals IncorporatedIndustry (pharma, biotech, devices)
- Study start
- 24 May 2017 (actual)
- Primary completion
- 9 Aug 2018 (actual)
- Study completion
- 9 Aug 2018 (actual)
- First posted
- 12 May 2017 (actual)
- Results
- Posted 12 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Study VX16-661-114 (Study 114) is a Phase 3b, randomized, double-blind, placebo-controlled, parallel-group, multicenter study in subjects aged 12 years and older with CF who are homozygous for the F508del mutation on the cystic fibrosis transmembrane conductance regulator gene (CFTR) gene and who discontinued treatment with Orkambi due to respiratory symptoms considered related to treatment. This study is designed to evaluate the safety and efficacy of Tezacaftor/Ivacaftor (TEZ/IVA).
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 |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboParticipants received placebo matched to TEZ/IVA fixed-dose combination tablet orally once daily in the morning followed by placebo matched to IVA tablet orally once daily in the evening for 56 days. |
| TEZ/IVA | Experimental | Drug: Tezacaftor/Ivacaftor, Drug: IvacaftorParticipants received TEZ 100 milligram (mg)/IVA 150 mg fixed-dose combination tablet orally once daily in the morning and IVA 150 mg tablet orally once daily in the evening for 56 days. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.
- Prior discontinuation of Orkambi, with at least 1 respiratory sign or symptom considered related to therapy.
- Resolution or stabilization of qualifying event(s) >28 days prior to Screening.
- Discontinuation of Orkambi therapy must have occurred within approximately 12 weeks from the first dose of Orkambi.
- Homozygous for F508del mutation in the CFTR gene as documented in the subject's medical record. If genotype documentation is not available in the medical record, genotyping will be performed during screening.
Key exclusion criteria (13 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.
- Recent rapid or progressive deterioration in respiratory status.
- Receiving continuous oxygen at >2L/min or on face-mask ventilation.
- Any protocol-defined exclusionary laboratory values at Screening.
- Child-Pugh Class B or C hepatic impairment.
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 |
|---|---|---|
| Tezacaftor/IvacaftorAlso: TEZ/IVA; VX-661/VX-770TEZ 100 mg/IVA 150 mg fixed-dose combination tablet. | Drug | TEZ/IVA |
| IvacaftorAlso: VX-770; IVAIVA 150 mg tablet. | Drug | TEZ/IVA |
| PlaceboPlacebo matched to TEZ/IVA fixed-dose combination tablet. | Drug | Placebo |
| PlaceboPlacebo matched to IVA tablet. | Drug | Placebo |
Primary outcome
Incidence of Respiratory Adverse Events of Special Interest (RAESIs)
Time frame: Day 1 up to Day 84
RAESIs included chest discomfort, dyspnea (shortness of breath), respiration abnormal (chest tightness), asthma, bronchial hyperreactivity, bronchospasm, and wheezing.
5 secondary outcomes
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Average of Day 28 and Day 56 Measurements
Time frame: Baseline, Day 28 and Day 56
Relative Change From Baseline in ppFEV1 at Average of Day 28 and Day 56 Measurements
Time frame: Baseline, Day 28 and Day 56
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Average of Day 28 and Day 56 Measurements
Time frame: Baseline, Day 28 and Day 56
Tolerability as Assessed by Number of Participants Who Discontinued Treatment
Time frame: Day 1 through Day 56
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Day 1 up to Day 84
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Sep 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.
53 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tezacaftor/Ivacaftor and Ivacaftor in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 53 sites in 3 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 8 inclusion and 13 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 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 53 sites in United States, France, Germany. 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 Sep 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?
Incidence of Respiratory Adverse Events of Special Interest (RAESIs) (time frame: Day 1 up to Day 84). 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 12 Sep 2019.