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A Study Evaluating the Safety and Efficacy of VX-659 Combination Therapy in Subjects With Cystic Fibrosis

This study is currently recruiting participants.
Verified November 2017 by Vertex Pharmaceuticals Incorporated
Sponsor:
ClinicalTrials.gov Identifier:
NCT03224351
First Posted: July 21, 2017
Last Update Posted: December 1, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
  Purpose
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 Intervention Phase
Cystic Fibrosis Drug: TEZ/IVA Drug: VX-659 Drug: IVA Drug: Matched Placebos Drug: TEZ Drug: VX-561 Phase 2

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Vertex Pharmaceuticals Incorporated:

Primary Outcome Measures:
  • Safety and tolerability as assessed by number of subjects with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: From baseline through safety follow-up (20 Weeks) ]
    Number of subjects with AEs and SAEs will be reported.

  • Absolute change in percent predicted forced expiratory volume in 1 second (ppFEV1) [ Time Frame: from baseline through Day 29 ]
    Absolute change in ppFEV1 will be reported.


Secondary Outcome Measures:
  • Absolute change in sweat chloride concentrations [ Time Frame: from baseline through Day 29 ]
    Absolute change in sweat chloride concentrations will be reported.

  • Relative change in ppFEV1 [ Time Frame: from baseline through Day 29 ]
    Relative change in ppFEV1 will be reported.

  • Absolute change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score [ Time Frame: from baseline at Day 29 ]
    The absolute change in CFQ-R respiratory domain score will be reported.

  • Maximum observed concentration (Cmax) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 [ Time Frame: from Day 1 through Day 29 ]
    Maximum plasma concentration [CMax] will be reported.

  • Area under the concentration versus time curve during a dosing interval (AUCtau) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 [ Time Frame: from Day 1 through Day 29 ]
    The area under the plasma concentration time curve over the dosing interval (AUCtau) will be reported.

  • Observed pre-dose concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 [ Time Frame: from Day 1 through Day 29 ]
    The observed predose concentration (Ctrough) will be reported.


Estimated Enrollment: 105
Actual Study Start Date: August 8, 2017
Estimated Study Completion Date: March 20, 2018
Estimated Primary Completion Date: March 20, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1: F/MF genotype -TC Low
Subjects will receive 80 mg of VX-659 qd in TC with TEZ and IVA for 4 weeks.
Drug: TEZ/IVA
100-mg TEZ/150-mg IVA fixed-dose combination (FDC) tablet for oral administration
Other Name: VX-661/VX-770
Drug: VX-659
80-mg VX-659 tablet for oral administration
Drug: IVA
150-mg IVA tablet for oral administration
Other Name: VX-770
Experimental: Part 1: F/MF genotype - TC Mid
Subjects will receive 240 mg of VX-659 qd in TC with TEZ and IVA for 4 weeks.
Drug: TEZ/IVA
100-mg TEZ/150-mg IVA fixed-dose combination (FDC) tablet for oral administration
Other Name: VX-661/VX-770
Drug: VX-659
80-mg VX-659 tablet for oral administration
Drug: IVA
150-mg IVA tablet for oral administration
Other Name: VX-770
Experimental: Part 1: F/MF genotype - TC High
Subjects will receive 400 mg VX-659 qd in TC with TEZ and IVA for 4 weeks.
Drug: TEZ/IVA
100-mg TEZ/150-mg IVA fixed-dose combination (FDC) tablet for oral administration
Other Name: VX-661/VX-770
Drug: VX-659
80-mg VX-659 tablet for oral administration
Drug: IVA
150-mg IVA tablet for oral administration
Other Name: VX-770
Placebo Comparator: Part 1: F/MF genotype - Placebo
Subjects will receive placebo for 4 weeks.
Drug: Matched Placebos
Placebo will be used as a comparator.
Experimental: Part 2: F/F genotype - TC
Subjects will receive 400 mg of VX-659 qd in TC with TEZ and IVA for 4 weeks.
Drug: TEZ/IVA
100-mg TEZ/150-mg IVA fixed-dose combination (FDC) tablet for oral administration
Other Name: VX-661/VX-770
Drug: VX-659
80-mg VX-659 tablet for oral administration
Drug: IVA
150-mg IVA tablet for oral administration
Other Name: VX-770
Active Comparator: Part 2: F/F genotype - TEZ/IVA
Subjects will receive TEZ and IVA for 4 weeks.
Drug: TEZ/IVA
100-mg TEZ/150-mg IVA fixed-dose combination (FDC) tablet for oral administration
Other Name: VX-661/VX-770
Drug: IVA
150-mg IVA tablet for oral administration
Other Name: VX-770
Drug: Matched Placebos
Placebo will be used as a comparator.
Experimental: Part 3: F/MF genotype - TC
Subjects will receive 400 mg of VX-659 qd in TC with TEZ and VX-561 for 4 weeks.
Drug: VX-659
80-mg VX-659 tablet for oral administration
Drug: TEZ
50-mg tablet for oral administration.
Drug: VX-561
50-mg VX-561 tablet for oral administration.
Other Name: CTP-656
Placebo Comparator: Part 3: F/MF genotype - Placebo
Subjects will receive placebo for 4 weeks.
Drug: Matched Placebos
Placebo will be used as a comparator.

  Eligibility

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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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
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


Contacts
Contact: Medical Information 617-341-6777 medicalinfo@vrtx.com

  Show 47 Study Locations
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
  More Information

Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT03224351     History of Changes
Other Study ID Numbers: VX16-659-101
2016-003585-11 ( EudraCT Number )
First Submitted: July 18, 2017
First Posted: July 21, 2017
Last Update Posted: December 1, 2017
Last Verified: November 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Fibrosis
Cystic 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