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A Study of VX-659 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-659/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

  • University of Alabama at Birmingham
  • Yale New Haven Medical Center
  • University of Miami/Miller School of Medicine
  • St. Luke's CF Center of Idaho
  • Advocate Children's Hospital- Park Ridge/ North Suburban Pulmonary and Critical Care Consultants
  • Indiana Clinical Research Center, IU Health University Hospital
  • The University of Iowa Hospitals and Clinics
  • The Johns Hopkins Hospital
  • Boston Children's Hospital
  • Helen DeVos Children's Hospital CF Center
  • Children's Mercy Hospital
  • Washington University School of Medicine / St. Louis Children's Hospital
  • Rutgers-Robert Wood Johnson Medical School
  • Albany Medical College
  • Northwell Health, Long Island Jewish Medical Center
  • Columbia University Medical Center
  • SUNY Upstate Medical University
  • Cincinnati Children's Hospital Medical Center
  • Respiratory Diseases of Children and Adolescents
  • Oregon Health & Science University
  • Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center
  • Sanford Research/ USD
  • University of Tennessee Medical Center-Adult Cystic Fibrosis Clinic
  • Children's Foundation Research Center/ Le Bonheur Children's Hospital
  • Vanderbilt University Medical Center
  • Baylor College of Medicine
  • University of Utah/ Primary Children's Medical Center
  • Seattle Children's Hospital
  • The Alfred Hospital
  • Royal Adelaide Hospital
  • Prince Charles Hospital
  • Institute for Respiratory Health Inc./ Sir Charles Gairdner Hospital
  • John Hunter Hospital & Hunter Medical Research Institute
  • Charite Paediatric Pulmonology Department
  • Pneumologische Praxis Pasing
  • Cork University Hospital
  • Our Lady's Children's Hospital
  • St. Vincent's University Hospital
  • Hospital Universitari Vall d Hebron
  • Hospital Universitari Vall d'Hebron Servicio de Broncoscopia
  • Hospital Universitario Virgen del Rocio
  • Papworth Hospital NHS Foundation Trust, Papworth Everard
  • Liverpool Heart and Chest Hospital
  • Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital
  • Wythenshawe Hospital
  • University Hospital Llandough

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

TEZ/IVA

VX-659/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-659 240 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 indicating fewer symptoms and better health-related quality of life.
Safety and Tolerability as Assessed Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Observed Pre-Dose Concentration (Ctrough) of VX-659, TEZ, TEZ Metabolite (M1-TEZ), and IVA

Full Information

First Posted
March 1, 2018
Last Updated
September 26, 2019
Sponsor
Vertex Pharmaceuticals Incorporated
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1. Study Identification

Unique Protocol Identification Number
NCT03460990
Brief Title
A Study of VX-659 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-659 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
September 2019
Overall Recruitment Status
Completed
Study Start Date
May 1, 2018 (Actual)
Primary Completion Date
September 26, 2018 (Actual)
Study Completion Date
October 8, 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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study will evaluate the efficacy of VX-659 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
116 (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-659/TEZ/IVA TC
Arm Type
Experimental
Arm Description
Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-659 240 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-659/TEZ/IVA
Other Intervention Name(s)
VX-659/VX-661/VX-770, VX-659/tezacaftor/ivacaftor
Intervention Description
Participants received VX-659/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 TEZ/IVA orally once daily in the morning.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Participants received placebo matched to VX-659/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 indicating fewer symptoms and better health-related quality of life.
Time Frame
From Baseline at Week 4
Title
Safety and Tolerability as Assessed 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-659, TEZ, TEZ Metabolite (M1-TEZ), and IVA
Time Frame
From 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
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Yale New Haven Medical Center
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06511
Country
United States
Facility Name
University of Miami/Miller School of Medicine
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
St. Luke's CF Center of Idaho
City
Boise
State/Province
Idaho
ZIP/Postal Code
83712
Country
United States
Facility Name
Advocate Children's Hospital- Park Ridge/ North Suburban Pulmonary and Critical Care Consultants
City
Niles
State/Province
Illinois
ZIP/Postal Code
60714
Country
United States
Facility Name
Indiana Clinical Research Center, IU Health University Hospital
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
The University of Iowa Hospitals and Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
The Johns Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Helen DeVos Children's Hospital CF Center
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49503
Country
United States
Facility Name
Children's Mercy Hospital
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Washington University School of Medicine / St. Louis Children's Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Rutgers-Robert Wood Johnson Medical School
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08901
Country
United States
Facility Name
Albany Medical College
City
Albany
State/Province
New York
ZIP/Postal Code
12208
Country
United States
Facility Name
Northwell Health, Long Island Jewish Medical Center
City
New Hyde Park
State/Province
New York
ZIP/Postal Code
11040
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
SUNY Upstate Medical University
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Respiratory Diseases of Children and Adolescents
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73211
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
Sanford Research/ USD
City
Sioux Falls
State/Province
South Dakota
ZIP/Postal Code
57105
Country
United States
Facility Name
University of Tennessee Medical Center-Adult Cystic Fibrosis Clinic
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37920
Country
United States
Facility Name
Children's Foundation Research Center/ Le Bonheur Children's Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38103
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Utah/ Primary Children's Medical Center
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
The Alfred Hospital
City
Melbourne
State/Province
Victoria
Country
Australia
Facility Name
Royal Adelaide Hospital
City
Adelaide
Country
Australia
Facility Name
Prince Charles Hospital
City
Chermside
Country
Australia
Facility Name
Institute for Respiratory Health Inc./ Sir Charles Gairdner Hospital
City
Nedlands
Country
Australia
Facility Name
John Hunter Hospital & Hunter Medical Research Institute
City
New Lambton Heights
Country
Australia
Facility Name
Charite Paediatric Pulmonology Department
City
Berlin
Country
Germany
Facility Name
Pneumologische Praxis Pasing
City
Muenchen
Country
Germany
Facility Name
Cork University Hospital
City
Dublin
Country
Ireland
Facility Name
Our Lady's Children's Hospital
City
Dublin
Country
Ireland
Facility Name
St. Vincent's University Hospital
City
Dublin
Country
Ireland
Facility Name
Hospital Universitari Vall d Hebron
City
Barcelona
Country
Spain
Facility Name
Hospital Universitari Vall d'Hebron Servicio de Broncoscopia
City
Barcelona
Country
Spain
Facility Name
Hospital Universitario Virgen del Rocio
City
Sevilla
Country
Spain
Facility Name
Papworth Hospital NHS Foundation Trust, Papworth Everard
City
Cambridge
Country
United Kingdom
Facility Name
Liverpool Heart and Chest Hospital
City
Liverpool
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
University Hospital Llandough
City
Penarth
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

A Study of VX-659 Combination Therapy in CF Subjects Homozygous for F508del (F/F)

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