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

Primary Purpose

Cystic Fibrosis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
VX-121
TEZ
VX-561
TEZ/IVA
IVA
Placebo
Sponsored by
Vertex Pharmaceuticals Incorporated
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cystic Fibrosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Keck Medical Center of University of Southern California
  • Kaiser Permanente
  • University of Kentucky.
  • Tulane Medical Center
  • Boston Children's Hospital
  • University of Minnesota
  • Columbia University Medical Center
  • Wake Forest University Baptist Medical Center
  • Nationwide Children's Hospital
  • Santiago Reyes, M.D.
  • Vanderbilt University Medical Center
  • University of Texas Health Science Center at San Antonio
  • Charite Paediatric Pulmonology Department
  • Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen
  • Pneumologisches Studienzentrum Muenchen-West
  • Academic Medical Center
  • HagaZiekenhuis van den Haag
  • University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis
  • UMC St. Radboud
  • Erasmus Medical Center
  • Hospital de Santa Maria
  • University Hospitals Birmingham NHS Foundation Trust
  • Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital
  • Wythenshawe Hospital
  • The Newcastle upon Tyne Hospitals NHS Foundation Trust, The Royal Victoria Infirmary
  • All Wales Adult Cystic Fibrosis Centre, University Hospital Llandough

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Placebo Comparator

Experimental

Experimental

Experimental

Active Comparator

Experimental

Arm Label

Part 1: Placebo

Part 1: VX-121/TEZ/VX-561 TC - Low Dose

Part 1: VX-121/TEZ/VX-561 TC - Medium Dose

Part 1: VX-121/TEZ/VX-561 TC - High Dose

Part 2: TEZ/IVA

Part 2: VX-121/TEZ/VX-561 TC - High Dose

Arm Description

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.

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

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

Secondary Outcome Measures

Absolute Change in Sweat Chloride (SwCl) Concentrations
Sweat samples were collected using an approved collection device.
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
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.
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)

Full Information

First Posted
April 10, 2019
Last Updated
March 29, 2023
Sponsor
Vertex Pharmaceuticals Incorporated
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1. Study Identification

Unique Protocol Identification Number
NCT03912233
Brief Title
A Study to Evaluate the Safety and Efficacy of VX-121 Combination Therapy in Subjects With Cystic Fibrosis
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
April 30, 2019 (Actual)
Primary Completion Date
December 10, 2019 (Actual)
Study Completion Date
December 10, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vertex Pharmaceuticals Incorporated

4. Oversight

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

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
87 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part 1: Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Part 1: VX-121/TEZ/VX-561 TC - Low Dose
Arm Type
Experimental
Arm Description
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
Arm Title
Part 1: VX-121/TEZ/VX-561 TC - Medium Dose
Arm Type
Experimental
Arm Description
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.
Arm Title
Part 1: VX-121/TEZ/VX-561 TC - High Dose
Arm Type
Experimental
Arm Description
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.
Arm Title
Part 2: TEZ/IVA
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Part 2: VX-121/TEZ/VX-561 TC - High Dose
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
VX-121
Intervention Description
Tablets for oral administration.
Intervention Type
Drug
Intervention Name(s)
TEZ
Other Intervention Name(s)
VX-661, Tezacaftor
Intervention Description
TEZ tablet for oral administration.
Intervention Type
Drug
Intervention Name(s)
VX-561
Other Intervention Name(s)
CTP-656, Deutivacaftor (D-IVA)
Intervention Description
Tablets for oral administration.
Intervention Type
Drug
Intervention Name(s)
TEZ/IVA
Other Intervention Name(s)
VX-661/VX-770, Tezacaftor/Ivacaftor
Intervention Description
Fixed-dose combination tablets for oral administration.
Intervention Type
Drug
Intervention Name(s)
IVA
Other Intervention Name(s)
VX-770, Ivacaftor
Intervention Description
Tablets for oral administration.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebos matched to VX-121, TEZ, and VX-561 for oral administration.
Primary Outcome Measure Information:
Title
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)
Title
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Description
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time Frame
From Baseline Through Day 29
Secondary Outcome Measure Information:
Title
Absolute Change in Sweat Chloride (SwCl) Concentrations
Description
Sweat samples were collected using an approved collection device.
Time Frame
From Baseline Through Day 29
Title
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
Description
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.
Time Frame
From Baseline at Day 29
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Keck Medical Center of University of Southern California
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Kaiser Permanente
City
Oakland
State/Province
California
ZIP/Postal Code
94611
Country
United States
Facility Name
University of Kentucky.
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Facility Name
Tulane Medical Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Wake Forest University Baptist Medical Center
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
Santiago Reyes, M.D.
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73112
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
University of Texas Health Science Center at San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229-3900
Country
United States
Facility Name
Charite Paediatric Pulmonology Department
City
Berlin
Country
Germany
Facility Name
Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen
City
Essen
Country
Germany
Facility Name
Pneumologisches Studienzentrum Muenchen-West
City
Muenchen
Country
Germany
Facility Name
Academic Medical Center
City
Amsterdam
Country
Netherlands
Facility Name
HagaZiekenhuis van den Haag
City
Den Haag
Country
Netherlands
Facility Name
University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis
City
Heidelberglaan
Country
Netherlands
Facility Name
UMC St. Radboud
City
Nijmegen
Country
Netherlands
Facility Name
Erasmus Medical Center
City
Rotterdam
Country
Netherlands
Facility Name
Hospital de Santa Maria
City
Lisbon
Country
Portugal
Facility Name
University Hospitals Birmingham NHS Foundation Trust
City
Birmingham
Country
United Kingdom
Facility Name
Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital
City
London
Country
United Kingdom
Facility Name
Wythenshawe Hospital
City
Manchester
Country
United Kingdom
Facility Name
The Newcastle upon Tyne Hospitals NHS Foundation Trust, The Royal Victoria Infirmary
City
Newcastle Upon Tyne
Country
United Kingdom
Facility Name
All Wales Adult Cystic Fibrosis Centre, University Hospital Llandough
City
Penarth
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing 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

Learn more about this trial

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

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