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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
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated

Brief 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 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).

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 ...

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 98 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis
Drug Information available for: Ivacaftor

Arm Intervention/treatment
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.
Drug: Placebo
Placebo matched to TEZ/IVA fixed-dose combination tablet.

Drug: Placebo
Placebo matched to IVA tablet.

Experimental: TEZ/IVA
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.
Drug: Tezacaftor/Ivacaftor
TEZ 100 mg/IVA 150 mg fixed-dose combination tablet.
Other Name: TEZ/IVA; VX-661/VX-770

Drug: Ivacaftor
IVA 150 mg tablet.
Other Name: VX-770; IVA




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. Tolerability as Assessed by Number of Participants Who Discontinued Treatment [ Time Frame: Day 1 through Day 56 ]
  5. Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Day 1 up to Day 84 ]


Information from the National Library of Medicine

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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
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

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


  Show 53 Study Locations
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
  Study Documents (Full-Text)

Documents provided by Vertex Pharmaceuticals Incorporated:
Study Protocol  [PDF] June 9, 2017
Statistical Analysis Plan  [PDF] May 21, 2018


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Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT03150719     History of Changes
Other Study ID Numbers: VX16-661-114
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Cystic Fibrosis
Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Ivacaftor
Chloride Channel Agonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action