A Study to Evaluate the Safety and Efficacy of VX-121 Combination Therapy in Subjects With Cystic Fibrosis

March 29, 2023 updated by: Vertex Pharmaceuticals Incorporated

A Phase 2, Randomized, Double-blind, Controlled Study to Evaluate the Safety and Efficacy of VX-121 Combination Therapy in Subjects Aged 18 Years and Older With Cystic Fibrosis

The purpose of this study is to evaluate the safety, tolerability and efficacy of VX-121 combination therapy in subjects with cystic fibrosis (CF).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

87

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

  • Germany
      • Berlin, Germany
        • Charite Paediatric Pulmonology Department
      • Essen, Germany
        • Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen
      • Muenchen, Germany
        • Pneumologisches Studienzentrum Muenchen-West
  • Netherlands
      • Amsterdam, Netherlands
        • Academic Medical Center
      • Den Haag, Netherlands
        • HagaZiekenhuis van Den Haag
      • Heidelberglaan, Netherlands
        • University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis
      • Nijmegen, Netherlands
        • UMC St. Radboud
      • Rotterdam, Netherlands
        • Erasmus Medical Center
  • Portugal
      • Lisbon, Portugal
        • Hospital De Santa Maria
  • United Kingdom
      • Birmingham, United Kingdom
        • University Hospitals Birmingham NHS Foundation Trust
      • London, United Kingdom
        • Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital
      • Manchester, United Kingdom
        • Wythenshawe Hospital
      • Newcastle Upon Tyne, United Kingdom
        • The Newcastle upon Tyne Hospitals NHS Foundation Trust, The Royal Victoria Infirmary
      • Penarth, United Kingdom
        • All Wales Adult Cystic Fibrosis Centre, University Hospital Llandough
  • United States
    • California
      • Los Angeles, California, United States, 90033
        • Keck Medical Center of University of Southern California
      • Oakland, California, United States, 94611
        • Kaiser Permanente
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky.
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Tulane Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Boston Children's Hospital
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Baptist Medical Center
    • Ohio
      • Columbus, Ohio, United States, 43205
        • Nationwide Children's Hospital
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73112
        • Santiago Reyes, M.D.
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center
    • Texas
      • San Antonio, Texas, United States, 78229-3900
        • University of Texas Health Science Center at San Antonio

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

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

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

Key Exclusion Criteria:

  • History of clinically significant cirrhosis with or without portal hypertension
  • 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

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: Sequential Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Part 1: Placebo
Participants received placebo matched to VX-121/TEZ/VX-561 triple combination (TC) for 4 weeks in the treatment period and placebo matched to TEZ/VX-561 for 18 days in the washout period.
Drug: Placebo
Placebos matched to VX-121, TEZ, and VX-561 for oral administration.
Experimental: Part 1: VX-121/TEZ/VX-561 TC - Low Dose
Participants received VX-121 5 milligram (mg) once daily (qd)/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period
Drug: TEZ
TEZ tablet for oral administration.
Other Names:
  • VX-661
  • Tezacaftor
Drug: VX-121
Tablets for oral administration.
Drug: VX-561
Tablets for oral administration.
Other Names:
  • CTP-656
  • Deutivacaftor (D-IVA)
Experimental: Part 1: VX-121/TEZ/VX-561 TC - Medium Dose
Participants received VX-121 10 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period.
Drug: TEZ
TEZ tablet for oral administration.
Other Names:
  • VX-661
  • Tezacaftor
Drug: VX-121
Tablets for oral administration.
Drug: VX-561
Tablets for oral administration.
Other Names:
  • CTP-656
  • Deutivacaftor (D-IVA)
Experimental: Part 1: VX-121/TEZ/VX-561 TC - High Dose
Participants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period.
Drug: TEZ
TEZ tablet for oral administration.
Other Names:
  • VX-661
  • Tezacaftor
Drug: VX-121
Tablets for oral administration.
Drug: VX-561
Tablets for oral administration.
Other Names:
  • CTP-656
  • Deutivacaftor (D-IVA)
Active Comparator: Part 2: TEZ/IVA
Following run-in period with TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) for 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the treatment period and TEZ 100 mg/IVA 150 mg q12h for 4 weeks in the washout period.
Drug: IVA
Tablets for oral administration.
Other Names:
  • VX-770
  • Ivacaftor
Drug: TEZ/IVA
Fixed-dose combination tablets for oral administration.
Other Names:
  • VX-661/VX-770
  • Tezacaftor/Ivacaftor
Experimental: Part 2: VX-121/TEZ/VX-561 TC - High Dose
Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the washout period.
Drug: TEZ
TEZ tablet for oral administration.
Other Names:
  • VX-661
  • Tezacaftor
Drug: VX-121
Tablets for oral administration.
Drug: VX-561
Tablets for oral administration.
Other Names:
  • CTP-656
  • Deutivacaftor (D-IVA)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
From Baseline Through Day 29
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: From Day 1 Through Safety Follow-up (up to Day 75 for Part 1 and up to Day 85 for Part 2)
From Day 1 Through Safety Follow-up (up to Day 75 for Part 1 and up to Day 85 for Part 2)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
From Baseline at Day 29
Absolute Change in Sweat Chloride (SwCl) Concentrations
Time Frame: From Baseline Through Day 29
Sweat samples were collected using an approved collection device.
From Baseline Through Day 29
Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561)
Time Frame: Pre-dose at Day 15 and Day 29
Pre-dose at 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)

April 30, 2019

Primary Completion (Actual)

December 10, 2019

Study Completion (Actual)

December 10, 2019

Study Registration Dates

First Submitted

April 10, 2019

First Submitted That Met QC Criteria

April 10, 2019

First Posted (Actual)

April 11, 2019

Study Record Updates

Last Update Posted (Actual)

April 20, 2023

Last Update Submitted That Met QC Criteria

March 29, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VX18-121-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/independent-research/clinical-trial-data-sharing

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

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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