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A Study Evaluating the Safety and Efficacy of VX-659 Combination Therapy in Subjects 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: NCT03224351
Recruitment Status : Completed
First Posted : July 21, 2017
Results First Posted : April 22, 2021
Last Update Posted : April 22, 2021
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated

Study Description
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Brief Summary:
This is a Phase 2, randomized, double-blind, placebo- and tezacaftor/ivacaftor (TEZ/IVA)-controlled, parallel-group, 3-part, multicenter study designed to evaluate the safety and efficacy of VX-659 in triple combination (TC) with TEZ and IVA in subjects with cystic fibrosis (CF) who are homozygous for the F508del mutation of the CF transmembrane conductance regulator (CFTR) gene (F/F genotype), or who are heterozygous for the F508del mutation and a minimal function (MF) CFTR mutation not likely to respond to TEZ, IVA, or TEZ/IVA (F/MF genotypes).

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: VX-659 Drug: TEZ/IVA Drug: IVA Drug: Placebo (matched to VX-659/TEZ/IVA) Drug: TEZ Drug: VX-561 Drug: Placebo (matched to VX-659/TEZ/VX-561) Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 124 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized, Double-blind, Controlled Study to Evaluate the Safety and Efficacy of VX-659 Combination Therapy in Subjects Aged 18 Years and Older With Cystic Fibrosis
Actual Study Start Date : August 8, 2017
Actual Primary Completion Date : February 28, 2018
Actual Study Completion Date : February 28, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis

Arms and Interventions
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Arm Intervention/treatment
Placebo Comparator: Part 1: Placebo
Participants received placebo matched to VX-659/TEZ/IVA in TC treatment period for 4 weeks and placebo matched TEZ/IVA in washout period for 4 days.
 Drug: Placebo (matched to VX-659/TEZ/IVA)
Placebo matched to VX-659 and TEZ/IVA.
Experimental: Part 1: VX-659/TEZ/IVA TC - Low Dose
Participants received VX-659 80 milligram (mg) once daily (qd)/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days.
 Drug: VX-659
Tablet for oral administration.

Drug: TEZ/IVA
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: VX-659/TEZ/IVA TC - Medium Dose
Participants received VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days.
 Drug: VX-659
Tablet for oral administration.

Drug: TEZ/IVA
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: VX-659/TEZ/IVA TC - High Dose
Participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days.
 Drug: VX-659
Tablet for oral administration.

Drug: TEZ/IVA
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: TEZ/IVA
Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks.
 Drug: TEZ/IVA
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 2: VX-659/TEZ/IVA TC
Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks.
 Drug: VX-659
Tablet for oral administration.

Drug: TEZ/IVA
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
Placebo Comparator: Part 3: Placebo
Participants received placebo matched to VX-659/TEZ/VX-561 in TC treatment period for 4 weeks.
 Drug: Placebo (matched to VX-659/TEZ/VX-561)
Placebo matched to VX-659, TEZ and VX-561.
Experimental: Part 3: VX-659/TEZ/VX-561 TC
Participants received VX-659 400 mg qd/TEZ 100 mg qd/VX-561 200 mg qd in TC treatment period for 4 weeks.
 Drug: VX-659
Tablet for oral administration.

Drug: TEZ
Tablet for oral administration.
Other Names:
  • VX-661
  • Tezacaftor

Drug: VX-561
Tablet for oral administration.
Other Name: CTP-656


Outcome Measures
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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 (up to Day 61 for Part 1, Day 85 for Part 2 and Day 57 for Part 3) ]
  2. Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) [ 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 [ Time Frame: From Baseline Through Day 29 ]
    Sweat samples were collected using an approved collection device.

  2. Relative Change in ppFEV1 [ 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.

  3. Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score [ 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.

  4. Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 [ Time Frame: Pre-dose at Day 15 and Day 29 ]

Eligibility Criteria
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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

Key Inclusion Criteria:

  • Body weight ≥35 kg.

  • Subjects must have an eligibleCFTR genotype.

    • Part 1 and Part 3: Heterozygous for F508del and an MF mutation (F/MF)
    • Part 2: Homozygous for F508del (F/F)
  • FEV1 value ≥40% and ≤90% of predicted mean for age, sex, and height

Key Exclusion Criteria:

  • History of clinically significant cirrhosis with or without portal hypertension.
  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency
  • Lung infection with organisms associated with a more rapid decline in pulmonary status.
  • History of solid organ or hematological transplantation.

Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations
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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): NCT03224351


Locations
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Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
  Study Documents (Full-Text)

Documents provided by Vertex Pharmaceuticals Incorporated:
Study Protocol  [PDF] September 1, 2017
Statistical Analysis Plan  [PDF] September 19, 2017

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT03224351    
Other Study ID Numbers: VX16-659-101
2016-003585-11 ( EudraCT Number )
First Posted: July 21, 2017    Key Record Dates
Results First Posted: April 22, 2021
Last Update Posted: April 22, 2021
Last Verified: February 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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VX-659
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