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A Study of VX-445 in Healthy Subjects and Subjects With Cystic Fibrosis

This study is currently recruiting participants.
Verified September 2017 by Vertex Pharmaceuticals Incorporated
Sponsor:
ClinicalTrials.gov Identifier:
NCT03227471
First Posted: July 24, 2017
Last Update Posted: October 25, 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 first-in-human and proof-of-concept study of VX-445. The study includes 6 parts. Parts A, B, and C will be conducted in healthy subjects. Parts D, E, and F will be conducted 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: IVA Drug: TEZ/IVA Drug: VX-445 Drug: Matched Placebo Drug: TEZ Drug: VX-561 Phase 1 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 1/2 Study of VX-445 in Healthy Subjects and Subjects 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 (up to 10 days after last dose for Part A, B, and C) ]
    Number of subjects with AEs and SAEs will be reported.

  • 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 (up to 35 days after last dose for Parts D, E, and F). ]
    Number of subjects with AEs and SAEs will be reported.

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


Secondary Outcome Measures:
  • Absolute change in sweat chloride concentrations [Parts C, D, E, and F only] [ Time Frame: from baseline through Day 29 ]
    Absolute change in sweat chloride concentrations will be reported.

  • Relative change in ppFEV1 [Parts D, E, and F only] [ 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 [Parts D, E, and F only] [ Time Frame: from baseline through Day 29 ]
    The absolute change in CFQ-R respiratory domain score will be reported.

  • Maximum observed concentration (Cmax) of VX-445,TEZ and metabolites (M1-TEZ and M2-TEZ), IVA and metabolites (M1-IVA and M6-IVA) and VX-561 [ Time Frame: from Day 1 through Day 43 ]
    Maximum plasma concentration [Cmax] will be reported.

  • Area under the concentration versus time curve during a dosing interval (AUCtau) of VX-445, TEZ and metabolites (M1-TEZ and M2-TEZ), IVA and metabolites (M1-IVA and M6-IVA) and VX-561 [ Time Frame: from Day 1 through Day 43 ]
    Area under the concentration versus time curve during a dosing interval (AUCtau) will be reported.

  • Observed pre-dose concentration (Ctrough) of VX-445, TEZ and metabolites (M1-TEZ and M2-TEZ), IVA and metabolites (M1-IVA and M6-IVA) and VX-561 [ Time Frame: from Day 1 through Day 43 ]
    Trough plasma concentration [Ctrough] will be reported.


Estimated Enrollment: 224
Actual Study Start Date: January 23, 2017
Estimated Study Completion Date: April 6, 2018
Estimated Primary Completion Date: April 6, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A: VX-445 in Healthy Subjects (HS)
Part A includes single dose escalation.
Drug: VX-445
VX-445 tablet for oral administration.
Placebo Comparator: Part A: Placebo Drug: Matched Placebo
Matched placebo.
Experimental: Part B: VX-445 in HS
Part B includes multiple-dose escalation.
Drug: VX-445
VX-445 tablet for oral administration.
Placebo Comparator: Part B: Placebo Drug: Matched Placebo
Matched placebo.
Experimental: Part C: VX-445 in Triple Combination (TC) with TEZ/IVA in HS
Multiple-dose escalation of VX-445 in TC with TEZ/IVA
Drug: IVA
150-mg IVA film-coated tablet for oral administration
Other Name: VX-770
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-445
VX-445 tablet for oral administration.
Placebo Comparator: Part C: Placebo Drug: Matched Placebo
Matched placebo.
Experimental: Part D1: F/MF genotypes TC
Subjects will receive 100 mg VX-445 qd in TC with TEZ and IVA for 4 weeks.
Drug: IVA
150-mg IVA film-coated tablet for oral administration
Other Name: VX-770
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-445
VX-445 tablet for oral administration.
Placebo Comparator: Part D1: Placebo
Subjects will receive placebo for 4 weeks.
Drug: Matched Placebo
Matched placebo.
Experimental: Part D2: F/MF genotypes TC-High
Subjects will receive VX-445 in TC with TEZ and IVA for 4 weeks.
Drug: IVA
150-mg IVA film-coated tablet for oral administration
Other Name: VX-770
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-445
VX-445 tablet for oral administration.
Experimental: Part D2: F/MF genotypes TC-Mid
Subjects will receive VX-445 in TC with TEZ and IVA for 4 weeks.
Drug: IVA
150-mg IVA film-coated tablet for oral administration
Other Name: VX-770
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-445
VX-445 tablet for oral administration.
Experimental: Part D2: F/MF genotypes TC-Low
Subjects will receive VX-445 in TC with TEZ and IVA for 4 weeks.
Drug: IVA
150-mg IVA film-coated tablet for oral administration
Other Name: VX-770
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-445
VX-445 tablet for oral administration.
Drug: Matched Placebo
Matched placebo.
Placebo Comparator: Part D2: Placebo Drug: Matched Placebo
Matched placebo.
Experimental: Part E: F/F genotype - TC
Subjects will receive VX-445 in TC with TEZ and IVA for 4 weeks
Drug: IVA
150-mg IVA film-coated tablet for oral administration
Other Name: VX-770
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-445
VX-445 tablet for oral administration.
Active Comparator: Part E: TEZ/IVA
Subjects will receive TEZ and IVA for 4 weeks.
Drug: IVA
150-mg IVA film-coated tablet for oral administration
Other Name: VX-770
Drug: TEZ/IVA
100-mg TEZ / 150-mg IVA fixed dose combination (FDC) tablet for oral administration.
Other Name: VX-661/VX-770
Drug: Matched Placebo
Matched placebo.
Experimental: Part F: F/MF genotypes - TC
Subjects will receive VX-445 in TC with TEZ and VX-561 for 4 weeks.
Drug: VX-445
VX-445 tablet for oral administration.
Drug: TEZ
50-mg tablet for oral administration.
Drug: VX-561
50-mg tablet for oral administration.
Other Name: CTP-656
Experimental: Part F: Placebo Drug: Matched Placebo
Matched placebo.

  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:   Yes
Criteria

Key Inclusion Criteria:

Parts A, B, and C:

  • Female subjects must be of non-childbearing potential.
  • Between the ages of 18 and 55 years, inclusive.
  • Body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive, and a total body weight >50 kg

Parts D, E, and F:

  • Body weight ≥35 kg.
  • Subjects must have an eligible CFTR genotype:

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

Key Exclusion Criteria:

Parts A, B, and C:

  • Any condition possibly affecting drug absorption.
  • History of febrile illness within 14 days before the first study drug dose.
  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Parts D, E, and F:

  • 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): NCT03227471


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

  Show 42 Study Locations
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
  More Information

Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT03227471     History of Changes
Other Study ID Numbers: VX16-445-001
2017-000797-11 ( EudraCT Number )
First Submitted: July 18, 2017
First Posted: July 24, 2017
Last Update Posted: October 25, 2017
Last Verified: September 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