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A Phase 3 Study to Evaluate the Efficacy and Safety of Ivacaftor and VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Mutation

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ClinicalTrials.gov Identifier: NCT02392234
Recruitment Status : Completed
First Posted : March 18, 2015
Results First Posted : June 12, 2018
Last Update Posted : June 12, 2018
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated

Tracking Information
First Submitted Date  ICMJE March 12, 2015
First Posted Date  ICMJE March 18, 2015
Results First Submitted Date  ICMJE March 14, 2018
Results First Posted Date  ICMJE June 12, 2018
Last Update Posted Date June 12, 2018
Study Start Date  ICMJE March 2015
Actual Primary Completion Date February 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 8, 2018)
Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Average of Week 4 and Week 8 [ Time Frame: Baseline, Week 4 and Week 8 of each treatment period ]
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Original Primary Outcome Measures  ICMJE
 (submitted: March 12, 2015)
Absolute Change From Study Baseline to Average of Week 4 and Week 8 Measurements in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: Baseline, Week 4 and Week 8 of each treatment period ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 8, 2018)
  • Absolute Change From Study Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Average of Week 4 and Week 8 [ Time Frame: Baseline, Week 4 and Week 8 of each treatment period ]
    The CFQ-R assessed respiratory symptoms on a scale with scores ranging from 0 to 100; where higher scores indicated fewer symptoms and better health-related quality of life.
  • Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Day 1 up to Week 28 ]
  • Relative Change From Study Baseline in ppFEV1 at Average of Week 4 and Week 8 [ Time Frame: Baseline, Week 4 and Week 8 of each treatment period ]
    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
  • Absolute Change From Study Baseline in Sweat Chloride at Average of Week 4 and Week 8 [ Time Frame: Baseline, Week 4 and Week 8 of each treatment period ]
  • Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1 VX-661), IVA and IVA Metabolite (M1 IVA) After Administration of VX-661/IVA Combination Therapy [ Time Frame: Pre-morning dose on Week 8 of each treatment period ]
  • Ctrough of IVA and IVA Metabolite (M1 IVA) After Administration of IVA Monotherapy [ Time Frame: Pre-morning dose on Week 8 of each treatment period ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 12, 2015)
  • Relative Change From Study Baseline to Average of Week 4 and Week 8 Measurements in FEV1 [ Time Frame: Baseline, Week 4 and Week 8 of each treatment period ]
  • Absolute Change From Study Baseline to Average of Week 4 and Week 8 Measurements in Sweat Chloride [ Time Frame: Baseline, Week 4 and Week 8 of each treatment period ]
  • Safety and tolerability assessments based on adverse events (AEs), clinical laboratory values, standard digital electrocardiograms (ECGs), vital signs, and pulse oximetry [ Time Frame: Baseline up to 28 days after last dose (up to 28 weeks) ]
  • Absolute Change From Study Baseline to Average of Week 4 and Week 8 Measurements in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score [ Time Frame: Baseline, Week 4 and Week 8 of each treatment period ]
  • Pharmacokinetic parameters; Area under the plasma concentration versus time curve (AUC), Peak Plasma Concentration (Cmax) of VX-661, M1-661, ivacaftor, and M1-ivacaftor, as determined by population analysis. [ Time Frame: Day 1 through Week 24 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 3 Study to Evaluate the Efficacy and Safety of Ivacaftor and VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Mutation
Official Title  ICMJE A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Efficacy and Safety of Ivacaftor and VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-CFTR Mutation, and a Second Allele With a CFTR Mutation Predicted to Have Residual Function
Brief Summary The purpose of this study is to evaluate the efficacy and safety of VX-661 in combination with ivacaftor (IVA, VX-770) and IVA monotherapy in participants with Cystic Fibrosis (CF) who are heterozygous for F508del-CFTR allele and a second allele with a CFTR mutation predicted to have residual function.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Cystic Fibrosis
Intervention  ICMJE
  • Drug: VX-661/Ivacaftor
    Fixed dose combination tablet, oral use
    Other Name: VX-661+VX-770
  • Drug: Ivacaftor
    Tablet, oral use
    Other Name: IVA, VX-770
  • Drug: Placebo matched to VX-661/ ivacaftor
    Fixed dose combination tablet, oral use
  • Drug: Placebo matched to Ivacaftor
    Tablet, oral use
Study Arms  ICMJE
  • Experimental: VX-661/Ivacaftor combination
    Interventions:
    • Drug: VX-661/Ivacaftor
    • Drug: Ivacaftor
    • Drug: Placebo matched to Ivacaftor
  • Experimental: Ivacaftor monotherapy
    Interventions:
    • Drug: Ivacaftor
    • Drug: Placebo matched to VX-661/ ivacaftor
  • Placebo Comparator: Placebo
    Interventions:
    • Drug: Placebo matched to VX-661/ ivacaftor
    • Drug: Placebo matched to Ivacaftor
Publications * Rowe SM, Daines C, Ringshausen FC, Kerem E, Wilson J, Tullis E, Nair N, Simard C, Han L, Ingenito EP, McKee C, Lekstrom-Himes J, Davies JC. Tezacaftor-Ivacaftor in Residual-Function Heterozygotes with Cystic Fibrosis. N Engl J Med. 2017 Nov 23;377(21):2024-2035. doi: 10.1056/NEJMoa1709847. Epub 2017 Nov 3.

*   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: May 8, 2018)
248
Original Estimated Enrollment  ICMJE
 (submitted: March 12, 2015)
300
Actual Study Completion Date  ICMJE February 2017
Actual Primary Completion Date February 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Heterozygous for F508del-CFTR and a second allele with a CFTR mutation predicted to have residual function
  • Forced Expiratory Volume in 1 Second (FEV1) greater than or equal to (≥) 40 percent (%) and less than or equal to (≤) 90% of predicted normal for age, sex, and height during screening
  • Sweat chloride value ≥60 millimole per liter (mmol/L) during screening OR as documented in the participant's medical record
  • Stable CF disease as judged by the investigator

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 participant
  • An acute upper or lower respiratory infection, pulmonary exacerbation
  • History of solid organ or hematological transplantation
  • Ongoing or prior participation in an investigational drug study (including studies investigating VX-661, lumacaftor [VX-809], and/or ivacaftor) within 30 days of screening
  • Pregnant and nursing females
  • Sexually active participants of reproductive potential who are not willing to follow the contraception requirements
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 Australia,   Belgium,   Canada,   France,   Germany,   Israel,   Italy,   Netherlands,   Switzerland,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02392234
Other Study ID Numbers  ICMJE VX14-661-108
2014-004788-18 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
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 May 2018

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