A Study to Evaluate Safety, Efficacy, and Tolerability of TEZ/IVA in Orkambi® (Lumacaftor/Ivacaftor) -Experienced Subjects With Cystic Fibrosis (CF)
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|ClinicalTrials.gov Identifier: NCT03150719|
Recruitment Status : Completed
First Posted : May 12, 2017
Results First Posted : September 12, 2019
Last Update Posted : September 12, 2019
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|Condition or disease||Intervention/treatment||Phase|
|Cystic Fibrosis||Drug: Tezacaftor/Ivacaftor Drug: Ivacaftor Drug: Placebo||Phase 3|
Expanded Access : An investigational treatment associated with this study has been approved for sale to the public. More info ...
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||98 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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|
|Actual Study Start Date :||May 24, 2017|
|Actual Primary Completion Date :||August 9, 2018|
|Actual Study Completion Date :||August 9, 2018|
Placebo Comparator: Placebo
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.
Placebo matched to TEZ/IVA fixed-dose combination tablet.
Placebo matched to IVA tablet.
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.
TEZ 100 mg/IVA 150 mg fixed-dose combination tablet.
Other Name: TEZ/IVA; VX-661/VX-770
IVA 150 mg tablet.
Other Name: VX-770; IVA
- 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.
- 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 ]FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
- Relative Change From Baseline in ppFEV1 at Average of Day 28 and Day 56 Measurements [ Time Frame: Baseline, Day 28 and Day 56 ]FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
- 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 ]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.
- 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 ]
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|Ages Eligible for Study:||12 Years and older (Child, Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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.
- 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.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03150719
Documents provided by Vertex Pharmaceuticals Incorporated:
|Responsible Party:||Vertex Pharmaceuticals Incorporated|
|Other Study ID Numbers:||
2017-000540-18 ( EudraCT Number )
|First Posted:||May 12, 2017 Key Record Dates|
|Results First Posted:||September 12, 2019|
|Last Update Posted:||September 12, 2019|
|Last Verified:||September 2019|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Digestive System Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Chloride Channel Agonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action