Back to resultsA Phase 3 Study to Evaluate the Efficacy and Safety of Ivacaftor and VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Mutation
Primary Purpose
Cystic Fibrosis
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
VX-661/Ivacaftor
Ivacaftor
Placebo matched to VX-661/ ivacaftor
Placebo matched to Ivacaftor
Sponsored by
About this trial
This is an interventional treatment trial for Cystic Fibrosis
Eligibility Criteria
Inclusion Criteria:
- Heterozygous for F508del-CFTR and a second allele with a CFTR mutation predicted to have residual function
- Forced Expiratory Volume in 1 Second (FEV1) greater than or equal to (≥) 40 percent (%) and less than or equal to (≤) 90% of predicted normal for age, sex, and height during screening
- Sweat chloride value ≥60 millimole per liter (mmol/L) during screening OR as documented in the participant's medical record
- Stable CF disease as judged by the investigator
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 participant
- An acute upper or lower respiratory infection, pulmonary exacerbation
- History of solid organ or hematological transplantation
- Ongoing or prior participation in an investigational drug study (including studies investigating VX-661, lumacaftor [VX-809], and/or ivacaftor) within 30 days of screening
- Pregnant and nursing females
- Sexually active participants of reproductive potential who are not willing to follow the contraception requirements
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
VX-661/Ivacaftor combination
Ivacaftor monotherapy
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Average of Week 4 and Week 8
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Secondary Outcome Measures
Absolute Change From Study Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Average of Week 4 and Week 8
The CFQ-R assessed respiratory symptoms on a scale with scores ranging from 0 to 100; where higher scores indicated fewer symptoms and better health-related quality of life.
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Relative Change From Study Baseline in ppFEV1 at Average of Week 4 and Week 8
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Absolute Change From Study Baseline in Sweat Chloride at Average of Week 4 and Week 8
Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1 VX-661), IVA and IVA Metabolite (M1 IVA) After Administration of VX-661/IVA Combination Therapy
Ctrough of IVA and IVA Metabolite (M1 IVA) After Administration of IVA Monotherapy
Full Information
NCT ID
NCT02392234
First Posted
March 12, 2015
Last Updated
May 8, 2018
Sponsor
Vertex Pharmaceuticals Incorporated
1. Study Identification
Unique Protocol Identification Number
NCT02392234
Brief Title
A Phase 3 Study to Evaluate the Efficacy and Safety of Ivacaftor and VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Mutation
Official Title
A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Efficacy and Safety of Ivacaftor and VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-CFTR Mutation, and a Second Allele With a CFTR Mutation Predicted to Have Residual Function
Study Type
Interventional
2. Study Status
Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
March 2015 (undefined)
Primary Completion Date
February 2017 (Actual)
Study Completion Date
February 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vertex Pharmaceuticals Incorporated
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of VX-661 in combination with ivacaftor (IVA, VX-770) and IVA monotherapy in participants with Cystic Fibrosis (CF) who are heterozygous for F508del-CFTR allele and a second allele with a CFTR mutation predicted to have residual function.
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
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
248 (Actual)
8. Arms, Groups, and Interventions
Arm Title
VX-661/Ivacaftor combination
Arm Type
Experimental
Arm Title
Ivacaftor monotherapy
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
VX-661/Ivacaftor
Other Intervention Name(s)
VX-661+VX-770
Intervention Description
Fixed dose combination tablet, oral use
Intervention Type
Drug
Intervention Name(s)
Ivacaftor
Other Intervention Name(s)
IVA, VX-770
Intervention Description
Tablet, oral use
Intervention Type
Drug
Intervention Name(s)
Placebo matched to VX-661/ ivacaftor
Intervention Description
Fixed dose combination tablet, oral use
Intervention Type
Drug
Intervention Name(s)
Placebo matched to Ivacaftor
Intervention Description
Tablet, oral use
Primary Outcome Measure Information:
Title
Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Average of Week 4 and Week 8
Description
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time Frame
Baseline, Week 4 and Week 8 of each treatment period
Secondary Outcome Measure Information:
Title
Absolute Change From Study Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Average of Week 4 and Week 8
Description
The CFQ-R assessed respiratory symptoms on a scale with scores ranging from 0 to 100; where higher scores indicated fewer symptoms and better health-related quality of life.
Time Frame
Baseline, Week 4 and Week 8 of each treatment period
Title
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame
Day 1 up to Week 28
Title
Relative Change From Study Baseline in ppFEV1 at Average of Week 4 and Week 8
Description
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time Frame
Baseline, Week 4 and Week 8 of each treatment period
Title
Absolute Change From Study Baseline in Sweat Chloride at Average of Week 4 and Week 8
Time Frame
Baseline, Week 4 and Week 8 of each treatment period
Title
Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1 VX-661), IVA and IVA Metabolite (M1 IVA) After Administration of VX-661/IVA Combination Therapy
Time Frame
Pre-morning dose on Week 8 of each treatment period
Title
Ctrough of IVA and IVA Metabolite (M1 IVA) After Administration of IVA Monotherapy
Time Frame
Pre-morning dose on Week 8 of each treatment period
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Heterozygous for F508del-CFTR and a second allele with a CFTR mutation predicted to have residual function
Forced Expiratory Volume in 1 Second (FEV1) greater than or equal to (≥) 40 percent (%) and less than or equal to (≤) 90% of predicted normal for age, sex, and height during screening
Sweat chloride value ≥60 millimole per liter (mmol/L) during screening OR as documented in the participant's medical record
Stable CF disease as judged by the investigator
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 participant
An acute upper or lower respiratory infection, pulmonary exacerbation
History of solid organ or hematological transplantation
Ongoing or prior participation in an investigational drug study (including studies investigating VX-661, lumacaftor [VX-809], and/or ivacaftor) within 30 days of screening
Pregnant and nursing females
Sexually active participants of reproductive potential who are not willing to follow the contraception requirements
Facility Information:
City
Birmingham
State/Province
Alabama
Country
United States
City
Phoenix
State/Province
Arizona
Country
United States
City
Tucson
State/Province
Arizona
Country
United States
City
Long Beach
State/Province
California
Country
United States
City
Oakland
State/Province
California
Country
United States
City
Palo Alto
State/Province
California
Country
United States
City
Sacramento
State/Province
California
Country
United States
City
Aurora
State/Province
Colorado
Country
United States
City
Denver
State/Province
Colorado
Country
United States
City
Gainesville
State/Province
Florida
Country
United States
City
Miami
State/Province
Florida
Country
United States
City
Orlando
State/Province
Florida
Country
United States
City
Pensacola
State/Province
Florida
Country
United States
City
Tampa
State/Province
Florida
Country
United States
City
Atlanta
State/Province
Georgia
Country
United States
City
Chicago
State/Province
Illinois
Country
United States
City
Park Ridge
State/Province
Illinois
Country
United States
City
Iowa City
State/Province
Iowa
Country
United States
City
Baltimore
State/Province
Maryland
Country
United States
City
Boston
State/Province
Massachusetts
Country
United States
City
Ann Arbor
State/Province
Michigan
Country
United States
City
Grand Rapids
State/Province
Michigan
Country
United States
City
Minneapolis
State/Province
Minnesota
Country
United States
City
Saint Louis
State/Province
Missouri
Country
United States
City
Lebanon
State/Province
New Hampshire
Country
United States
City
New York
State/Province
New York
Country
United States
City
Syracuse
State/Province
New York
Country
United States
City
Valhalla
State/Province
New York
Country
United States
City
Chapel Hill
State/Province
North Carolina
Country
United States
City
Akron
State/Province
Ohio
Country
United States
City
Cincinnati
State/Province
Ohio
Country
United States
City
Cleveland
State/Province
Ohio
Country
United States
City
Toledo
State/Province
Ohio
Country
United States
City
Portland
State/Province
Oregon
Country
United States
City
Philadelphia
State/Province
Pennsylvania
Country
United States
City
Pittsburgh
State/Province
Pennsylvania
Country
United States
City
Charleston
State/Province
South Carolina
Country
United States
City
Sioux Falls
State/Province
South Dakota
Country
United States
City
Memphis
State/Province
Tennessee
Country
United States
City
Austin
State/Province
Texas
Country
United States
City
Dallas
State/Province
Texas
Country
United States
City
Tyler
State/Province
Texas
Country
United States
City
Salt Lake City
State/Province
Utah
Country
United States
City
Norfolk
State/Province
Virginia
Country
United States
City
Seattle
State/Province
Washington
Country
United States
City
Spokane
State/Province
Washington
Country
United States
City
Milwaukee
State/Province
Wisconsin
Country
United States
City
Adelaide
Country
Australia
City
Melbourne
Country
Australia
City
South Brisbane
Country
Australia
City
Westmead
Country
Australia
City
Gent
Country
Belgium
City
Montreal
Country
Canada
City
Quebec City
Country
Canada
City
Toronto
Country
Canada
City
Vancouver
Country
Canada
City
Marseille cedex 20
State/Province
Bouches-du-Rhone
Country
France
City
Montpellier cedex 5
State/Province
Herault
Country
France
City
Rennes cedex 09
State/Province
Ille Et Vilaine
Country
France
City
Lille cedex
State/Province
Nord
Country
France
City
Paris cedex 14
State/Province
Paris
Country
France
City
Paris cedex 15
State/Province
Paris
Country
France
City
Bron
State/Province
Rhone
Country
France
City
Bordeaux Cedex
Country
France
City
Muenchen
State/Province
Bayern
Country
Germany
City
Munchen
State/Province
Bayern
Country
Germany
City
Hannover
State/Province
Niedersachsen
Country
Germany
City
Essen
State/Province
Nordrhein Westfalen
Country
Germany
City
Jena
State/Province
Thueringen
Country
Germany
City
Berlin
Country
Germany
City
Haifa
Country
Israel
City
Jerusalem
Country
Israel
City
Petach-Tikva
Country
Israel
City
Ramat-Gan
Country
Israel
City
Ancona
Country
Italy
City
Milano
Country
Italy
City
Orbassano
Country
Italy
City
Potenza
Country
Italy
City
Roma
Country
Italy
City
Verona
Country
Italy
City
Amsterdam
Country
Netherlands
City
Den Haag
Country
Netherlands
City
Rotterdam
Country
Netherlands
City
Utrecht
Country
Netherlands
City
Bern
Country
Switzerland
City
St Gallen
Country
Switzerland
City
Zuerich
Country
Switzerland
City
Exeter
State/Province
Devon
Country
United Kingdom
City
London
State/Province
Greater London
Country
United Kingdom
City
Manchester
State/Province
Greater Manchester
Country
United Kingdom
City
Southampton
State/Province
Hampshire
Country
United Kingdom
City
Liverpool
State/Province
Lancashire
Country
United Kingdom
City
Glasgow
State/Province
Strathclyde
Country
United Kingdom
City
Leeds
State/Province
West Yorkshire
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
33331662
Citation
Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.
Results Reference
derived
PubMed Identifier
29099333
Citation
Rowe SM, Daines C, Ringshausen FC, Kerem E, Wilson J, Tullis E, Nair N, Simard C, Han L, Ingenito EP, McKee C, Lekstrom-Himes J, Davies JC. Tezacaftor-Ivacaftor in Residual-Function Heterozygotes with Cystic Fibrosis. N Engl J Med. 2017 Nov 23;377(21):2024-2035. doi: 10.1056/NEJMoa1709847. Epub 2017 Nov 3.
Results Reference
derived
Learn more about this trial
A Phase 3 Study to Evaluate the Efficacy and Safety of Ivacaftor and VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Mutation
We'll reach out to this number within 24 hrs