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

January 7, 2021 updated by: Vertex Pharmaceuticals Incorporated

A Phase 2, Randomized, Double Blind, Controlled Study to Evaluate the Safety of VX-152 Combination Therapy in Adults With Cystic Fibrosis

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

80

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States
    • California
      • La Jolla, California, United States
      • Los Angeles, California, United States
    • Florida
      • Orlando, Florida, United States
    • Illinois
      • Chicago, Illinois, United States
      • Peoria, Illinois, United States
    • Missouri
      • Saint Louis, Missouri, United States
    • North Carolina
      • Chapel Hill, North Carolina, United States
    • Ohio
      • Akron, Ohio, United States
      • Cleveland, Ohio, United States
    • Oregon
      • Portland, Oregon, United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States
    • South Carolina
      • Charleston, South Carolina, United States
    • Texas
      • Fort Worth, Texas, United States
      • Houston, Texas, United States
    • Wisconsin
      • Madison, Wisconsin, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Part 1: Placebo
Drug: Placebo
Placebo matched to VX-152.
Drug: Placebo
Placebo matched to VX-152/TEZ/IVA triple combination (TC).
Experimental: Part 1 Cohort 1A: TC
Drug: IVA
Tablet for oral administration.
Other Names:
  • VX-770
  • Ivacaftor
Drug: TEZ/IVA
Fixed-dose combination tablet for oral administration.
Other Names:
  • VX-661/VX-770
  • Tezacaftor/Ivacaftor
Drug: VX-152
Tablet for oral administration.
Experimental: Part 1 Cohort 1B: TC
Drug: IVA
Tablet for oral administration.
Other Names:
  • VX-770
  • Ivacaftor
Drug: TEZ/IVA
Fixed-dose combination tablet for oral administration.
Other Names:
  • VX-661/VX-770
  • Tezacaftor/Ivacaftor
Drug: VX-152
Tablet for oral administration.
Experimental: Part 1 Cohort 1C: TC
Drug: IVA
Tablet for oral administration.
Other Names:
  • VX-770
  • Ivacaftor
Drug: TEZ/IVA
Fixed-dose combination tablet for oral administration.
Other Names:
  • VX-661/VX-770
  • Tezacaftor/Ivacaftor
Drug: VX-152
Tablet for oral administration.
Active Comparator: Part 2 Cohort 2A: TEZ/IVA
Drug: IVA
Tablet for oral administration.
Other Names:
  • VX-770
  • Ivacaftor
Drug: TEZ/IVA
Fixed-dose combination tablet for oral administration.
Other Names:
  • VX-661/VX-770
  • Tezacaftor/Ivacaftor
Drug: Placebo
Placebo matched to VX-152.
Drug: Placebo
Placebo matched to VX-152/TEZ/IVA triple combination (TC).
Experimental: Part 2 Cohort 2A: TC
Drug: IVA
Tablet for oral administration.
Other Names:
  • VX-770
  • Ivacaftor
Drug: TEZ/IVA
Fixed-dose combination tablet for oral administration.
Other Names:
  • VX-661/VX-770
  • Tezacaftor/Ivacaftor
Drug: VX-152
Tablet for oral administration.
Active Comparator: Part 2 Cohort 2B: TEZ/IVA
Drug: IVA
Tablet for oral administration.
Other Names:
  • VX-770
  • Ivacaftor
Drug: TEZ/IVA
Fixed-dose combination tablet for oral administration.
Other Names:
  • VX-661/VX-770
  • Tezacaftor/Ivacaftor
Drug: Placebo
Placebo matched to VX-152.
Drug: Placebo
Placebo matched to VX-152/TEZ/IVA triple combination (TC).
Experimental: Part 2 Cohort 2B: TC
Drug: IVA
Tablet for oral administration.
Other Names:
  • VX-770
  • Ivacaftor
Drug: TEZ/IVA
Fixed-dose combination tablet for oral administration.
Other Names:
  • VX-661/VX-770
  • Tezacaftor/Ivacaftor
Drug: VX-152
Tablet for oral administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
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.
From Baseline at Day 15
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.
From Baseline Through Day 29

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
From Baseline at Day 15
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.
From Baseline Through Day 29
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.
From Baseline at Day 15
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.
From Baseline Through Day 29
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.
From Baseline at Day 15
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.
From Baseline at Day 29
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
Pre-dose at Day 8, Day 15 and Day 29

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vertex Pharmaceuticals Incorporated

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2016

Primary Completion (Actual)

January 1, 2018

Study Completion (Actual)

January 1, 2018

Study Registration Dates

First Submitted

October 26, 2016

First Submitted That Met QC Criteria

October 28, 2016

First Posted (Estimate)

November 1, 2016

Study Record Updates

Last Update Posted (Actual)

January 28, 2021

Last Update Submitted That Met QC Criteria

January 7, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VX16-152-102

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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