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Study to Evaluate Safety and Efficacy of VX-661 in Combination With Ivacaftor in Subjects With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation With an Open-Label Expansion

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ClinicalTrials.gov Identifier: NCT02070744
Recruitment Status : Completed
First Posted : February 25, 2014
Results First Posted : April 13, 2018
Last Update Posted : April 13, 2018
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated

Tracking Information
First Submitted Date  ICMJE February 21, 2014
First Posted Date  ICMJE February 25, 2014
Results First Submitted Date  ICMJE March 14, 2018
Results First Posted Date  ICMJE April 13, 2018
Last Update Posted Date April 13, 2018
Study Start Date  ICMJE March 2014
Actual Primary Completion Date May 27, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 14, 2018)
  • PC Phase: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline (PC Phase) up to 112 days ]
    AE: Any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as Non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, Inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first dose of study drug through the end of study participation considered treatment-emergent. Baseline was defined as Day 1 of PC Phase.
  • OLE Phase: Number of Participants With Treatment-Emergent AEs and SAEs [ Time Frame: Baseline (OLE Phase) up to 364 days ]
    AE: Any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as Non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, Inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first dose of study drug through the end of study participation considered treatment-emergent. Baseline was defined as Day 1 of the OLE Phase.
Original Primary Outcome Measures  ICMJE
 (submitted: February 21, 2014)
Safety as determined by adverse events (AEs), physical examination, clinical laboratory values, standard digital electrocardiograms (ECGs), vital signs and pulse oximetry [ Time Frame: baseline through Week 16 ]
Change History Complete list of historical versions of study NCT02070744 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 14, 2018)
  • PC Phase: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 12 [ Time Frame: Baseline (PC Phase), Through Week 12 ]
    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Baseline was defined as Day 1 of PC Phase.
  • OLE Phase: Absolute Change From Baseline in Percent Predicted FEV1 Through Week 40 [ Time Frame: Baseline (OLE Phase), Through Week 40 ]
    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Baseline was defined as Day 1 of the OLE Phase.
  • PC Phase: Relative Change From Baseline in Percent Predicted FEV1 Through Week 12 [ Time Frame: Baseline (PC Phase), Through Week 12 ]
    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Baseline was defined as Day 1 of PC Phase.
  • OLE Phase: Relative Change From Baseline in Percent Predicted FEV1 Through Week 40 [ Time Frame: Baseline (OLE Phase), Through Week 40 ]
    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Baseline was defined as Day 1 of the OLE Phase.
  • PC Phase: Absolute Change From Baseline in Sweat Chloride Through Week 12 [ Time Frame: Baseline (PC Phase), Through Week 12 ]
    Sweat samples were collected using an approved collection device. Baseline was defined as Day 1 of PC Phase.
  • OLE Phase: Absolute Change From Baseline in Sweat Chloride Through Week 40 [ Time Frame: Baseline (OLE Phase), Through Week 40 ]
    Sweat samples were collected using an approved collection device. Baseline was defined as Day 1 of the OLE Phase.
  • PC Phase: Absolute Change From Baseline in Body Weight at Week 12 [ Time Frame: Baseline (PC Phase), Week 12 ]
    Baseline was defined as Day 1 of PC Phase.
  • OLE Phase: Absolute Change From Baseline in Body Weight at Week 40 [ Time Frame: Baseline (OLE Phase), Week 40 ]
    Baseline was defined as Day 1 of the OLE Phase.
  • PC Phase: Absolute Change From Baseline Body Mass Index (BMI) at Week 12 [ Time Frame: Baseline (PC Phase), Week 12 ]
    BMI was calculated using following formula: BMI = Weight in kg/height in square meter (m^2). Baseline was defined as Day 1 of PC Phase.
  • OLE Phase: Absolute Change From Baseline BMI at Week 40 [ Time Frame: Baseline (OLE Phase), Week 40 ]
    BMI was calculated using following formula: BMI = Weight in kg/height in m^2. Baseline was defined as Day 1 of the OLE Phase.
  • PC Phase: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 12 [ Time Frame: Baseline (PC Phase), Through Week 12 ]
    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 (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Baseline was defined as Day 1 of PC Phase.
  • OLE Phase: Absolute Change From Baseline in CFQ-R Respiratory Domain Score Through Week 40 [ Time Frame: Baseline (OLE Phase), Through Week 40 ]
    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 (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Baseline was defined as Day 1 of the OLE Phase.
  • PC Phase: Maximum Plasma Concentration (Cmax) of VX-661 and IVA [ Time Frame: Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85 ]
  • PC Phase: Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24h) of VX-661 [ Time Frame: Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85 ]
    Pharmacokinetic (PK) sampling was performed up to 12 hours post-dose on Day 85. For Arm VX-661 50 mg q12h + IVA 150 mg q12h (VX-661 q12h regimen), area under the concentration versus time curve from time 0 to 12 hours (AUC0-12h) was multiplied by 2 to obtain AUC0-24h.
  • PC Phase: Area Under the Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12h) of IVA [ Time Frame: Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85 ]
  • PC Phase: Time to Reach Cmax (Tmax) of VX-661 and IVA [ Time Frame: Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 21, 2014)
  • Absolute change in percent predicted forced expiratory volume in 1 second (FEV1) [ Time Frame: from basline through Week 12 ]
  • Relative change in percent predicted FEV1 [ Time Frame: from baseline through Week 12 ]
  • Absolute change in body weight [ Time Frame: From baseline at Week 12 ]
  • Absolute change in body mass index (BMI) [ Time Frame: From baseline at Week 12 ]
  • Absolute change in the respiratory domain of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) [ Time Frame: baseline through Week 12 ]
  • PK parameters estimates of VX-661 and ivacaftor and their respective metabolites, derived from plasma concentration-time data [ Time Frame: Day 1 through Week 16 ]
  • Absolute change in sweat chloride [ Time Frame: from baseline through Week 12 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Evaluate Safety and Efficacy of VX-661 in Combination With Ivacaftor in Subjects With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation With an Open-Label Expansion
Official Title  ICMJE A Phase 2, Randomized, Multicenter, Double Blind, Placebo Controlled Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of VX-661 in Combination With Ivacaftor for 12 Weeks in Subjects With Cystic Fibrosis, Homozygous for the F508del CFTR Mutation With an Open-Label Extension
Brief Summary The objective of this study was to evaluate the safety and efficacy of VX-661in combination with ivacaftor in participants with cystic fibrosis (CF) who are homozygous for F508del cystic fibrosis transmembrane conductance regulator (CFTR) mutation
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Cystic Fibrosis
Intervention  ICMJE
  • Drug: VX-661
    Tablet, oral use
  • Drug: Ivacaftor
    Film coated tablet, oral use
  • Drug: Placebo matched to VX-661
    Tablet, oral use
  • Drug: Placebo matched to Ivacaftor
    Film coated tablet, oral use
Study Arms  ICMJE
  • Experimental: PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h
    Participants received VX-661 50 milligram (mg) tablet plus Ivacaftor (IVA) 150 mg tablet every 12 hours (q12h) for 12 weeks.
    Interventions:
    • Drug: VX-661
    • Drug: Ivacaftor
  • Placebo Comparator: PC Phase: VX 661 placebo q12h + IVA placebo q12h
    Participants received placebo matched to VX-661 tablet plus placebo matched to IVA tablet q12h for 12 weeks.
    Interventions:
    • Drug: Placebo matched to VX-661
    • Drug: Placebo matched to Ivacaftor
  • Experimental: PC Phase: VX-661 100 mg qd + IVA 150 mg q12h
    Participants received two VX-661 50 mg tablets once daily (qd) plus IVA 150 mg tablet q12h for 12 weeks.
    Interventions:
    • Drug: VX-661
    • Drug: Ivacaftor
  • Placebo Comparator: PC Phase: VX -661 placebo qd + IVA placebo q12h
    Participants received two placebo matched to VX-661 tablets qd plus placebo matched to IVA tablet q12h for 12 weeks.
    Interventions:
    • Drug: Placebo matched to VX-661
    • Drug: Placebo matched to Ivacaftor
  • Experimental: OLE Phase: VX-661 100 mg qd + IVA 150 mg q12h
    Participants who completed 12 week PC phase underwent a washout period of at least 4 weeks before entering the OLE phase and received two VX-661 50 mg tablets qd plus IVA 150 mg tablet q12h for 48 weeks in OLE phase.
    Interventions:
    • Drug: VX-661
    • 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: October 17, 2014)
40
Original Estimated Enrollment  ICMJE
 (submitted: February 21, 2014)
60
Actual Study Completion Date  ICMJE May 27, 2016
Actual Primary Completion Date May 27, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Homozygous for the F508del CFTR mutation
  • FEV1 ≥40% and ≤90% of predicted normal for age, sex, and height
  • 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
  • Pregnant and nursing females: Females of childbearing potential must have a negative pregnancy test at screening and Day 1 of the PC Phase and Day -7 or Day 1 of the OLE Phase (whichever was applicable)
  • Sexually active participants of reproductive potential who are not willing to follow the contraception requirements
  • The participant or a close relative of the participant is the investigator or sub investigator, research assistant, pharmacist, study coordinator, or other staff directly involved with the conduct of the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (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 United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02070744
Other Study ID Numbers  ICMJE VX13-661-103
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 March 2018

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