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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

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).

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: VX-152 Drug: TEZ/IVA Drug: IVA Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized, Double Blind, Controlled Study to Evaluate the Safety of VX-152 Combination Therapy in Adults With Cystic Fibrosis
Actual Study Start Date : November 2016
Actual Primary Completion Date : January 2018
Actual Study Completion Date : January 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: Part 1: Placebo Drug: Placebo
Placebo matched to VX-152/TEZ/IVA triple combination (TC).

Experimental: Part 1 Cohort 1A: TC 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

Experimental: Part 1 Cohort 1B: TC 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

Experimental: Part 1 Cohort 1C: TC 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

Active Comparator: Part 2 Cohort 2A: TEZ/IVA 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.

Experimental: Part 2 Cohort 2A: TC 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

Active Comparator: Part 2 Cohort 2B: TEZ/IVA 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.

Experimental: Part 2 Cohort 2B: TC 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




Primary Outcome Measures :
  1. 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) ]
  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.

  3. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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): NCT02951195


Locations
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United States, Alabama
Birmingham, Alabama, United States
United States, California
La Jolla, California, United States
Los Angeles, California, United States
United States, Florida
Orlando, Florida, United States
United States, Illinois
Chicago, Illinois, United States
Peoria, Illinois, United States
United States, Missouri
Saint Louis, Missouri, United States
United States, North Carolina
Chapel Hill, North Carolina, United States
United States, Ohio
Akron, Ohio, United States
Cleveland, Ohio, United States
United States, Oregon
Portland, Oregon, United States
United States, Pennsylvania
Philadelphia, Pennsylvania, United States
United States, South Carolina
Charleston, South Carolina, United States
United States, Texas
Fort Worth, Texas, United States
Houston, Texas, United States
United States, Wisconsin
Madison, Wisconsin, United States
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
  Study Documents (Full-Text)

Documents provided by Vertex Pharmaceuticals Incorporated:
Study Protocol  [PDF] April 14, 2017
Statistical Analysis Plan  [PDF] July 27, 2017

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Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT02951195    
Other Study ID Numbers: VX16-152-102
First Posted: November 1, 2016    Key Record Dates
Results First Posted: January 28, 2021
Last Update Posted: January 28, 2021
Last Verified: January 2021
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