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A Study Evaluating the Safety of VX-152 Combination Therapy in Adults With Cystic Fibrosis

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ClinicalTrials.gov Identifier: NCT02951195
Recruitment Status : Completed
First Posted : November 1, 2016
Results First Posted : January 28, 2021
Last Update Posted : January 28, 2021
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated

Tracking Information
First Submitted Date  ICMJE October 26, 2016
First Posted Date  ICMJE November 1, 2016
Results First Submitted Date  ICMJE January 7, 2021
Results First Posted Date  ICMJE January 28, 2021
Last Update Posted Date January 28, 2021
Actual Study Start Date  ICMJE November 2016
Actual Primary Completion Date January 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 7, 2021)
  • Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: Day 1 Through Safety Follow-up Visit (Up to Day 43 for Part 1 and Day 71 for Part 2) ]
  • Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 15 for Part 1 and Part 2 Cohort 2A [ Time Frame: From Baseline at Day 15 ]
    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
  • Absolute Change in ppFEV1 Through Day 29 for Part 2 Cohort 2B [ Time Frame: From Baseline Through Day 29 ]
    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Original Primary Outcome Measures  ICMJE
 (submitted: October 28, 2016)
Safety and Tolerability assessments as determined by number of subjects with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: from baseline up to 8 Weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 7, 2021)
  • Absolute Change in Sweat Chloride Concentrations at Day 15 for Part 1 and Part 2 Cohort 2A [ Time Frame: From Baseline at Day 15 ]
    Sweat samples were collected using an approved collection device.
  • Absolute Change in Sweat Chloride Concentrations Through Day 29 for Part 2 Cohort 2B [ Time Frame: From Baseline Through Day 29 ]
    Sweat samples were collected using an approved collection device.
  • Relative Change in ppFEV1 at Day 15 for Part 1 and Part 2 Cohort 2A [ Time Frame: From Baseline at Day 15 ]
    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
  • Relative Change in ppFEV1 Through Day 29 for Part 2 Cohort 2B [ Time Frame: From Baseline Through Day 29 ]
    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 at Day 15 for Part 1 and Part 2 Cohort 2A [ Time Frame: From Baseline at Day 15 ]
    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.
  • Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 29 for Part 2 Cohort 2B [ Time Frame: From Baseline at Day 29 ]
    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.
  • Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA [ Time Frame: Pre-dose at Day 8, Day 15 and Day 29 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 28, 2016)
  • Absolute change in sweat chloride concentrations [ Time Frame: From Baseline at Day 15 ]
  • Absolute change in percent predicted forced expiratory volume in 1 second (ppFEV1) [ Time Frame: from baseline at Day 15 ]
  • Relative change in ppFEV1 [ Time Frame: From Baseline at Day 15 ]
  • Absolute change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score [ Time Frame: From Baseline at Day 15 ]
  • Maximum observed concentration (Cmax) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA (μg/mL) [ Time Frame: Day 1 through Day 15 ]
  • Area under the concentration versus time curve during a dosing interval (AUCtau) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA (μg.h/mL) [ Time Frame: Day 1 through Day 15 ]
  • Observed pre-dose concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA (μg/mL) [ Time Frame: Day 1 through Day 15 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Evaluating the Safety of VX-152 Combination Therapy in Adults With Cystic Fibrosis
Official Title  ICMJE A Phase 2, Randomized, Double Blind, Controlled Study to Evaluate the Safety of VX-152 Combination Therapy in Adults With Cystic Fibrosis
Brief Summary This is a Phase 2, randomized, double blind, placebo and active-controlled, parallel group, multicenter study designed to evaluate the safety and tolerability of VX-152 in Triple Combination (TC) with tezacaftor (TEZ; VX-661) and ivacaftor (IVA; VX-770) in subjects with cystic fibrosis (CF) who are heterozygous for the F508del mutation and a minimal function (MF) CFTR mutation not likely to respond to TEZ and/or IVA therapy (F508del/MF), or who are homozygous for the F508del mutation of the CF transmembrane conductance regulator (CFTR) gene (F508del/F508del).
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-152
    Tablet for oral administration.
  • Drug: TEZ/IVA
    Fixed-dose combination tablet for oral administration.
    Other Names:
    • VX-661/VX-770
    • Tezacaftor/Ivacaftor
  • Drug: IVA
    Tablet for oral administration.
    Other Names:
    • VX-770
    • Ivacaftor
  • Drug: Placebo
    Placebo matched to VX-152.
  • Drug: Placebo
    Placebo matched to VX-152/TEZ/IVA triple combination (TC).
Study Arms  ICMJE
  • Placebo Comparator: Part 1: Placebo
    Intervention: Drug: Placebo
  • Experimental: Part 1 Cohort 1A: TC
    Interventions:
    • Drug: VX-152
    • Drug: TEZ/IVA
    • Drug: IVA
  • Experimental: Part 1 Cohort 1B: TC
    Interventions:
    • Drug: VX-152
    • Drug: TEZ/IVA
    • Drug: IVA
  • Experimental: Part 1 Cohort 1C: TC
    Interventions:
    • Drug: VX-152
    • Drug: TEZ/IVA
    • Drug: IVA
  • Active Comparator: Part 2 Cohort 2A: TEZ/IVA
    Interventions:
    • Drug: TEZ/IVA
    • Drug: IVA
    • Drug: Placebo
  • Experimental: Part 2 Cohort 2A: TC
    Interventions:
    • Drug: VX-152
    • Drug: TEZ/IVA
    • Drug: IVA
  • Active Comparator: Part 2 Cohort 2B: TEZ/IVA
    Interventions:
    • Drug: TEZ/IVA
    • Drug: IVA
    • Drug: Placebo
  • Experimental: Part 2 Cohort 2B: TC
    Interventions:
    • Drug: VX-152
    • Drug: TEZ/IVA
    • Drug: IVA
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: February 21, 2018)
80
Original Estimated Enrollment  ICMJE
 (submitted: October 28, 2016)
60
Actual Study Completion Date  ICMJE January 2018
Actual Primary Completion Date January 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Willing and able to comply with scheduled visits, treatment pan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.
  • Body weight ≥35 kg.
  • Sweat chloride value ≥ 60 mmol/L from test results obtained during screening.
  • Subjects must have an eligible CFTR genotype:

    • Cohorts 1A, 1B, 1C: Heterozygous for F508del and a minimal function mutation known or predicted not to respond to TEZ and/or IVA.
    • Cohorts 2A, 2B: Homozygous for F508del.
  • Subjects must have an FEV1 ≥40% and ≤90% of predicted normal for age, sex, and height at the Screening Visit.
  • Stable CF disease as judged by the investigator.
  • Willing to remain on a stable CF medication regimen through the planned end of treatment or if applicable the Safety Follow-up Visit.

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.
  • History of cirrhosis with portal hypertension.
  • Risk factors for Torsade de Pointes.
  • History of hemolysis.
  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency assessed at Screening.
  • Clinically significant abnormal laboratory values at screening.
  • An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 28 days before the first dose of study drug.
  • Lung infection with organisms associated with a more rapid decline in pulmonary status.
  • An acute illness not related to CF within 14 days before the first dose of study drug.
  • A standard digital ECG demonstrating QTc >450 msec at screening.
  • History of solid organ or hematological transplantation.
  • History or evidence of cataract or lens opacity determined to be clinically significant by the ophthalmologist or optometrist, based on the ophthalmologic examination during the Screening Period.
  • History of alcohol or drug abuse in the past year, including but not limited to, cannabis, cocaine, and opiates, as deemed by the investigator.
  • Ongoing or prior participation in an investigational drug study with certain exceptions.
  • Use of commercially available CFTR modulator within 14 days before screening (applies only to Cohorts 1A, 1B, and 1C).
  • Pregnant or nursing females: Females of childbearing potential must have a negative pregnancy test at screening and Day 1.
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 NCT02951195
Other Study ID Numbers  ICMJE VX16-152-102
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 January 2021

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