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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

Tracking Information
First Submitted Date  ICMJE May 3, 2017
First Posted Date  ICMJE May 12, 2017
Results First Submitted Date  ICMJE August 8, 2019
Results First Posted Date  ICMJE September 12, 2019
Last Update Posted Date September 12, 2019
Actual Study Start Date  ICMJE May 24, 2017
Actual Primary Completion Date August 9, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 11, 2019)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 9, 2017)
Incidence of respiratory adverse events (AEs) [ Time Frame: At Day 56 ]
Number and proportion of subjects with respiratory AEs will be reported
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 11, 2019)
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 9, 2017)
  • Absolute change in percent predicted forced expiratory volume in 1 second (ppFEV1) [ Time Frame: from baseline to the average of the Day 28 and Day 56 measurements ]
    Absolute change in ppFEV1 will be reported. FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
  • Relative change in ppFEV1 [ Time Frame: from baseline to the average of the Day 28 and Day 56 measurements ]
    Relative change in ppFEV1 will be reported. FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
  • Absolute change in Cystic Fibrosis Questionnaire Revised (CFQ-R) respiratory domain score [ Time Frame: from baseline to the average of the 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 will assess respiratory symptoms (for example, coughing, congestion, wheezing), which will be scaled on a 0-100 scale where higher scores indicate fewer symptoms and better health-related quality of life.
  • Tolerability, defined as the number and proportion of study participants who discontinue treatment [ Time Frame: through Day 56 ]
    Number and proportion of subjects who discontinued TEZ/IVA will be reported.
  • Safety assessments based on the number of subjects with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Day 1 up to safety follow-up (up to 28 days after last dose of study drug) ]
    Measured as number and proportion of subjects with AEs, abnormal laboratory values, vital signs or pulse oximetry
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate Safety, Efficacy, and Tolerability of TEZ/IVA in Orkambi® (Lumacaftor/Ivacaftor) -Experienced Subjects With Cystic Fibrosis (CF)
Official Title  ICMJE 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
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Cystic Fibrosis
Intervention  ICMJE
  • 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
  • Drug: Placebo
    Placebo matched to TEZ/IVA fixed-dose combination tablet.
  • Drug: Placebo
    Placebo matched to IVA tablet.
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Placebo
    • Drug: Placebo
  • 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.
    Interventions:
    • Drug: Tezacaftor/Ivacaftor
    • Drug: Ivacaftor
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 28, 2018)
98
Original Estimated Enrollment  ICMJE
 (submitted: May 9, 2017)
126
Actual Study Completion Date  ICMJE August 9, 2018
Actual Primary Completion Date August 9, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Germany,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03150719
Other Study ID Numbers  ICMJE VX16-661-114
2017-000540-18 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Vertex Pharmaceuticals Incorporated
Study Sponsor  ICMJE Vertex Pharmaceuticals Incorporated
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Vertex Pharmaceuticals Incorporated
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP