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A Study of VX-445 Combination Therapy in CF Subjects Homozygous for F508del (F/F)

Primary Purpose

Cystic Fibrosis

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
VX-445/TEZ/IVA
TEZ/IVA
IVA
Placebo
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

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

Key Inclusion Criteria:

  • Homozygous for the F508del mutation (F/F)
  • Forced expiratory volume in 1 second (FEV1) value ≥40% and ≤90% of predicted mean for age, sex, and height

Key Exclusion Criteria:

  • Clinically significant cirrhosis with or without portal hypertension
  • Lung infection with organisms associated with a more rapid decline in pulmonary status
  • Solid organ or hematological transplantation

Other protocol defined Inclusion/Exclusion criteria may apply

Sites / Locations

  • Banner University of Arizona Medical Center
  • University of Arkansas for Medical Sciences
  • Miller Children's Hospital/ Long Beach Memorial
  • Children's Hospital Los Angeles
  • Valley Children's Hospital
  • National Jewish Health
  • Joe DiMaggio Cystic Fibrosis & Pulmonary Center/ Joe DiMaggio Children's Hospital/ Memorial Regional Hospital
  • Central Florida Pulmonary Group, PA
  • Nemours Children's Hospital
  • Tampa General Hospital Cardiac and Lung Transplant Clinic
  • Northwestern Memorial Hospital
  • Saint Francis Medical Center/ Children's Hospital of Illinoise/OSF
  • Tulane Medical Center
  • Massachusetts General Hospital Cystic Fibrosis Center Clinical Research Center
  • Harper University Hospital
  • New York Medical College
  • UNC Marisco Clinical Research Center
  • Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center
  • Nationwide Children's Hospital
  • Dayton Children's Hospital
  • ProMedica Toledo Hospital/ Toledo Children's Hospital/ Pediatric Pulmonary & Cystic Fibrosis Center
  • University of Oklahoma Health Sciences Center
  • Children's Hospital of Philadelphia
  • Medical University of South Carolina
  • The University of Texas Southwestern Medical Center
  • Vermont Lung Center
  • University of Virginia Primary Care Center
  • West Virginia University
  • Cliniques Universitaires de Bruxelles Hopital Erasme
  • Universitair Ziekenhuis Brussel - Campus Jette
  • UZ Antwerpen
  • Universitair Ziekenhuis Gent
  • Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
  • Academic Medical Center
  • HagaZiekenhuis van den Haag
  • University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis
  • UMC St. Radboud
  • Erasmus Medical Center
  • The Royal Belfast Hospital for Sick Children
  • Heart of England NHS Foundation Trust, Birmingham Heartlands Hospital
  • Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital
  • Leeds General Infirmary
  • King's College Hospital
  • Southampton General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

TEZ/IVA

VX-445/TEZ/IVA TC

Arm Description

Following a run-in period of 4 weeks with Tezacaftor (TEZ)/Ivacaftor (IVA), participants received TEZ 100 milligram (mg)/IVA 150 mg as fixed-dose combination (FDC) tablet in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the triple combination (TC) treatment period.

Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-445 200 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period.

Outcomes

Primary Outcome Measures

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)
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 indicate fewer symptoms and better health-related quality of life.
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Observed Pre-Dose Concentration (Ctrough) of VX-445, TEZ, TEZ Metabolite (M1-TEZ), and IVA

Full Information

First Posted
May 2, 2018
Last Updated
January 24, 2020
Sponsor
Vertex Pharmaceuticals Incorporated
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1. Study Identification

Unique Protocol Identification Number
NCT03525548
Brief Title
A Study of VX-445 Combination Therapy in CF Subjects Homozygous for F508del (F/F)
Official Title
A Phase 3, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Who Are Homozygous for the F508del Mutation (F/F)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
August 3, 2018 (Actual)
Primary Completion Date
December 28, 2018 (Actual)
Study Completion Date
December 28, 2018 (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

5. Study Description

Brief Summary
This study will evaluate the efficacy of VX-445 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are homozygous for the F508del mutation (F/F)

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 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
113 (Actual)

8. Arms, Groups, and Interventions

Arm Title
TEZ/IVA
Arm Type
Active Comparator
Arm Description
Following a run-in period of 4 weeks with Tezacaftor (TEZ)/Ivacaftor (IVA), participants received TEZ 100 milligram (mg)/IVA 150 mg as fixed-dose combination (FDC) tablet in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the triple combination (TC) treatment period.
Arm Title
VX-445/TEZ/IVA TC
Arm Type
Experimental
Arm Description
Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-445 200 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period.
Intervention Type
Drug
Intervention Name(s)
VX-445/TEZ/IVA
Other Intervention Name(s)
VX-445/VX-661/VX-770, VX-445/tezacaftor/ivacaftor
Intervention Description
Participants received VX-445/TEZ/IVA orally once daily in the morning.
Intervention Type
Drug
Intervention Name(s)
TEZ/IVA
Other Intervention Name(s)
VX-661/VX-770, tezacaftor/ivacaftor
Intervention Description
Participants received TEZ/IVA orally once daily in the morning.
Intervention Type
Drug
Intervention Name(s)
IVA
Other Intervention Name(s)
VX-770, ivacaftor
Intervention Description
Participants received IVA orally once daily in the evening.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Participants received placebo matched to VX-445/TEZ/IVA orally once daily in the morning.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Participants received placebo matched TEZ/IVA orally once daily in the morning.
Primary Outcome Measure Information:
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 at Week 4
Secondary Outcome Measure Information:
Title
Absolute Change in Sweat Chloride (SwCl)
Description
Sweat samples were collected using an approved collection device.
Time Frame
From Baseline at Week 4
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 indicate fewer symptoms and better health-related quality of life.
Time Frame
From Baseline at Week 4
Title
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame
From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)
Title
Observed Pre-Dose Concentration (Ctrough) of VX-445, TEZ, TEZ Metabolite (M1-TEZ), and IVA
Time Frame
Day 1 and Week 4

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Homozygous for the F508del mutation (F/F) Forced expiratory volume in 1 second (FEV1) value ≥40% and ≤90% of predicted mean for age, sex, and height Key Exclusion Criteria: Clinically significant cirrhosis with or without portal hypertension Lung infection with organisms associated with a more rapid decline in pulmonary status Solid organ or hematological transplantation Other protocol defined Inclusion/Exclusion criteria may apply
Facility Information:
Facility Name
Banner University of Arizona Medical Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
University of Arkansas for Medical Sciences
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
Miller Children's Hospital/ Long Beach Memorial
City
Long Beach
State/Province
California
ZIP/Postal Code
90806
Country
United States
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Valley Children's Hospital
City
Madera
State/Province
California
ZIP/Postal Code
93636
Country
United States
Facility Name
National Jewish Health
City
Denver
State/Province
Colorado
ZIP/Postal Code
80206
Country
United States
Facility Name
Joe DiMaggio Cystic Fibrosis & Pulmonary Center/ Joe DiMaggio Children's Hospital/ Memorial Regional Hospital
City
Hollywood
State/Province
Florida
ZIP/Postal Code
33021
Country
United States
Facility Name
Central Florida Pulmonary Group, PA
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States
Facility Name
Nemours Children's Hospital
City
Orlando
State/Province
Florida
ZIP/Postal Code
32827
Country
United States
Facility Name
Tampa General Hospital Cardiac and Lung Transplant Clinic
City
Tampa
State/Province
Florida
ZIP/Postal Code
33606
Country
United States
Facility Name
Northwestern Memorial Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Saint Francis Medical Center/ Children's Hospital of Illinoise/OSF
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61637
Country
United States
Facility Name
Tulane Medical Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Massachusetts General Hospital Cystic Fibrosis Center Clinical Research Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Harper University Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
New York Medical College
City
Valhalla
State/Province
New York
ZIP/Postal Code
10595
Country
United States
Facility Name
UNC Marisco Clinical Research Center
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27517
Country
United States
Facility Name
Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
Dayton Children's Hospital
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45404
Country
United States
Facility Name
ProMedica Toledo Hospital/ Toledo Children's Hospital/ Pediatric Pulmonary & Cystic Fibrosis Center
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43606
Country
United States
Facility Name
University of Oklahoma Health Sciences Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
The University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Vermont Lung Center
City
Colchester
State/Province
Vermont
ZIP/Postal Code
05446
Country
United States
Facility Name
University of Virginia Primary Care Center
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Facility Name
West Virginia University
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26506
Country
United States
Facility Name
Cliniques Universitaires de Bruxelles Hopital Erasme
City
Brussels
Country
Belgium
Facility Name
Universitair Ziekenhuis Brussel - Campus Jette
City
Brussels
Country
Belgium
Facility Name
UZ Antwerpen
City
Edegem
Country
Belgium
Facility Name
Universitair Ziekenhuis Gent
City
Gent
Country
Belgium
Facility Name
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
City
Leuven
Country
Belgium
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
The Royal Belfast Hospital for Sick Children
City
Belfast
Country
United Kingdom
Facility Name
Heart of England NHS Foundation Trust, Birmingham Heartlands Hospital
City
Birmingham
Country
United Kingdom
Facility Name
Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital
City
Exeter
Country
United Kingdom
Facility Name
Leeds General Infirmary
City
Leeds
Country
United Kingdom
Facility Name
King's College Hospital
City
London
Country
United Kingdom
Facility Name
Southampton General Hospital
City
Southampton
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
31679946
Citation
Heijerman HGM, McKone EF, Downey DG, Van Braeckel E, Rowe SM, Tullis E, Mall MA, Welter JJ, Ramsey BW, McKee CM, Marigowda G, Moskowitz SM, Waltz D, Sosnay PR, Simard C, Ahluwalia N, Xuan F, Zhang Y, Taylor-Cousar JL, McCoy KS; VX17-445-103 Trial Group. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1940-1948. doi: 10.1016/S0140-6736(19)32597-8. Epub 2019 Oct 31. Erratum In: Lancet. 2020 May 30;395(10238):1694.
Results Reference
derived

Learn more about this trial

A Study of VX-445 Combination Therapy in CF Subjects Homozygous for F508del (F/F)

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