Back to resultsStudy to Evaluate Safety and Efficacy of VX-661 in Combination With Ivacaftor in Subjects With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation With an Open-Label Expansion
Primary Purpose
Cystic Fibrosis
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
VX-661
Ivacaftor
Placebo matched to VX-661
Placebo matched to Ivacaftor
Sponsored by
About this trial
This is an interventional treatment trial for Cystic Fibrosis focused on measuring CF
Eligibility Criteria
Inclusion Criteria:
- Homozygous for the F508del CFTR mutation
- FEV1 ≥40% and ≤90% of predicted normal for age, sex, and height
- 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
- Pregnant and nursing females: Females of childbearing potential must have a negative pregnancy test at screening and Day 1 of the PC Phase and Day -7 or Day 1 of the OLE Phase (whichever was applicable)
- Sexually active participants of reproductive potential who are not willing to follow the contraception requirements
- The participant or a close relative of the participant is the investigator or sub investigator, research assistant, pharmacist, study coordinator, or other staff directly involved with the conduct of the study.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Arm Label
PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h
PC Phase: VX 661 placebo q12h + IVA placebo q12h
PC Phase: VX-661 100 mg qd + IVA 150 mg q12h
PC Phase: VX -661 placebo qd + IVA placebo q12h
OLE Phase: VX-661 100 mg qd + IVA 150 mg q12h
Arm Description
Participants received VX-661 50 milligram (mg) tablet plus Ivacaftor (IVA) 150 mg tablet every 12 hours (q12h) for 12 weeks.
Participants received placebo matched to VX-661 tablet plus placebo matched to IVA tablet q12h for 12 weeks.
Participants received two VX-661 50 mg tablets once daily (qd) plus IVA 150 mg tablet q12h for 12 weeks.
Participants received two placebo matched to VX-661 tablets qd plus placebo matched to IVA tablet q12h for 12 weeks.
Participants who completed 12 week PC phase underwent a washout period of at least 4 weeks before entering the OLE phase and received two VX-661 50 mg tablets qd plus IVA 150 mg tablet q12h for 48 weeks in OLE phase.
Outcomes
Primary Outcome Measures
PC Phase: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
AE: Any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as Non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, Inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first dose of study drug through the end of study participation considered treatment-emergent. Baseline was defined as Day 1 of PC Phase.
OLE Phase: Number of Participants With Treatment-Emergent AEs and SAEs
AE: Any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as Non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, Inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first dose of study drug through the end of study participation considered treatment-emergent. Baseline was defined as Day 1 of the OLE Phase.
Secondary Outcome Measures
PC Phase: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 12
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Baseline was defined as Day 1 of PC Phase.
OLE Phase: Absolute Change From Baseline in Percent Predicted FEV1 Through Week 40
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Baseline was defined as Day 1 of the OLE Phase.
PC Phase: Relative Change From Baseline in Percent Predicted FEV1 Through Week 12
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Baseline was defined as Day 1 of PC Phase.
OLE Phase: Relative Change From Baseline in Percent Predicted FEV1 Through Week 40
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Baseline was defined as Day 1 of the OLE Phase.
PC Phase: Absolute Change From Baseline in Sweat Chloride Through Week 12
Sweat samples were collected using an approved collection device. Baseline was defined as Day 1 of PC Phase.
OLE Phase: Absolute Change From Baseline in Sweat Chloride Through Week 40
Sweat samples were collected using an approved collection device. Baseline was defined as Day 1 of the OLE Phase.
PC Phase: Absolute Change From Baseline in Body Weight at Week 12
Baseline was defined as Day 1 of PC Phase.
OLE Phase: Absolute Change From Baseline in Body Weight at Week 40
Baseline was defined as Day 1 of the OLE Phase.
PC Phase: Absolute Change From Baseline Body Mass Index (BMI) at Week 12
BMI was calculated using following formula: BMI = Weight in kg/height in square meter (m^2). Baseline was defined as Day 1 of PC Phase.
OLE Phase: Absolute Change From Baseline BMI at Week 40
BMI was calculated using following formula: BMI = Weight in kg/height in m^2. Baseline was defined as Day 1 of the OLE Phase.
PC Phase: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 12
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 (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Baseline was defined as Day 1 of PC Phase.
OLE Phase: Absolute Change From Baseline in CFQ-R Respiratory Domain Score Through Week 40
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 (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Baseline was defined as Day 1 of the OLE Phase.
PC Phase: Maximum Plasma Concentration (Cmax) of VX-661 and IVA
PC Phase: Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24h) of VX-661
Pharmacokinetic (PK) sampling was performed up to 12 hours post-dose on Day 85. For Arm VX-661 50 mg q12h + IVA 150 mg q12h (VX-661 q12h regimen), area under the concentration versus time curve from time 0 to 12 hours (AUC0-12h) was multiplied by 2 to obtain AUC0-24h.
PC Phase: Area Under the Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12h) of IVA
PC Phase: Time to Reach Cmax (Tmax) of VX-661 and IVA
Full Information
NCT ID
NCT02070744
First Posted
February 21, 2014
Last Updated
March 14, 2018
Sponsor
Vertex Pharmaceuticals Incorporated
1. Study Identification
Unique Protocol Identification Number
NCT02070744
Brief Title
Study to Evaluate Safety and Efficacy of VX-661 in Combination With Ivacaftor in Subjects With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation With an Open-Label Expansion
Official Title
A Phase 2, Randomized, Multicenter, Double Blind, Placebo Controlled Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of VX-661 in Combination With Ivacaftor for 12 Weeks in Subjects With Cystic Fibrosis, Homozygous for the F508del CFTR Mutation With an Open-Label Extension
Study Type
Interventional
2. Study Status
Record Verification Date
March 2018
Overall Recruitment Status
Completed
Study Start Date
March 2014 (undefined)
Primary Completion Date
May 27, 2016 (Actual)
Study Completion Date
May 27, 2016 (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 objective of this study was to evaluate the safety and efficacy of VX-661in combination with ivacaftor in participants with cystic fibrosis (CF) who are homozygous for F508del cystic fibrosis transmembrane conductance regulator (CFTR) mutation
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
Keywords
CF
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h
Arm Type
Experimental
Arm Description
Participants received VX-661 50 milligram (mg) tablet plus Ivacaftor (IVA) 150 mg tablet every 12 hours (q12h) for 12 weeks.
Arm Title
PC Phase: VX 661 placebo q12h + IVA placebo q12h
Arm Type
Placebo Comparator
Arm Description
Participants received placebo matched to VX-661 tablet plus placebo matched to IVA tablet q12h for 12 weeks.
Arm Title
PC Phase: VX-661 100 mg qd + IVA 150 mg q12h
Arm Type
Experimental
Arm Description
Participants received two VX-661 50 mg tablets once daily (qd) plus IVA 150 mg tablet q12h for 12 weeks.
Arm Title
PC Phase: VX -661 placebo qd + IVA placebo q12h
Arm Type
Placebo Comparator
Arm Description
Participants received two placebo matched to VX-661 tablets qd plus placebo matched to IVA tablet q12h for 12 weeks.
Arm Title
OLE Phase: VX-661 100 mg qd + IVA 150 mg q12h
Arm Type
Experimental
Arm Description
Participants who completed 12 week PC phase underwent a washout period of at least 4 weeks before entering the OLE phase and received two VX-661 50 mg tablets qd plus IVA 150 mg tablet q12h for 48 weeks in OLE phase.
Intervention Type
Drug
Intervention Name(s)
VX-661
Intervention Description
Tablet, oral use
Intervention Type
Drug
Intervention Name(s)
Ivacaftor
Intervention Description
Film coated tablet, oral use
Intervention Type
Drug
Intervention Name(s)
Placebo matched to VX-661
Intervention Description
Tablet, oral use
Intervention Type
Drug
Intervention Name(s)
Placebo matched to Ivacaftor
Intervention Description
Film coated tablet, oral use
Primary Outcome Measure Information:
Title
PC Phase: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
AE: Any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as Non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, Inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first dose of study drug through the end of study participation considered treatment-emergent. Baseline was defined as Day 1 of PC Phase.
Time Frame
Baseline (PC Phase) up to 112 days
Title
OLE Phase: Number of Participants With Treatment-Emergent AEs and SAEs
Description
AE: Any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as Non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, Inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first dose of study drug through the end of study participation considered treatment-emergent. Baseline was defined as Day 1 of the OLE Phase.
Time Frame
Baseline (OLE Phase) up to 364 days
Secondary Outcome Measure Information:
Title
PC Phase: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 12
Description
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Baseline was defined as Day 1 of PC Phase.
Time Frame
Baseline (PC Phase), Through Week 12
Title
OLE Phase: Absolute Change From Baseline in Percent Predicted FEV1 Through Week 40
Description
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Baseline was defined as Day 1 of the OLE Phase.
Time Frame
Baseline (OLE Phase), Through Week 40
Title
PC Phase: Relative Change From Baseline in Percent Predicted FEV1 Through Week 12
Description
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Baseline was defined as Day 1 of PC Phase.
Time Frame
Baseline (PC Phase), Through Week 12
Title
OLE Phase: Relative Change From Baseline in Percent Predicted FEV1 Through Week 40
Description
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Baseline was defined as Day 1 of the OLE Phase.
Time Frame
Baseline (OLE Phase), Through Week 40
Title
PC Phase: Absolute Change From Baseline in Sweat Chloride Through Week 12
Description
Sweat samples were collected using an approved collection device. Baseline was defined as Day 1 of PC Phase.
Time Frame
Baseline (PC Phase), Through Week 12
Title
OLE Phase: Absolute Change From Baseline in Sweat Chloride Through Week 40
Description
Sweat samples were collected using an approved collection device. Baseline was defined as Day 1 of the OLE Phase.
Time Frame
Baseline (OLE Phase), Through Week 40
Title
PC Phase: Absolute Change From Baseline in Body Weight at Week 12
Description
Baseline was defined as Day 1 of PC Phase.
Time Frame
Baseline (PC Phase), Week 12
Title
OLE Phase: Absolute Change From Baseline in Body Weight at Week 40
Description
Baseline was defined as Day 1 of the OLE Phase.
Time Frame
Baseline (OLE Phase), Week 40
Title
PC Phase: Absolute Change From Baseline Body Mass Index (BMI) at Week 12
Description
BMI was calculated using following formula: BMI = Weight in kg/height in square meter (m^2). Baseline was defined as Day 1 of PC Phase.
Time Frame
Baseline (PC Phase), Week 12
Title
OLE Phase: Absolute Change From Baseline BMI at Week 40
Description
BMI was calculated using following formula: BMI = Weight in kg/height in m^2. Baseline was defined as Day 1 of the OLE Phase.
Time Frame
Baseline (OLE Phase), Week 40
Title
PC Phase: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 12
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 (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Baseline was defined as Day 1 of PC Phase.
Time Frame
Baseline (PC Phase), Through Week 12
Title
OLE Phase: Absolute Change From Baseline in CFQ-R Respiratory Domain Score Through Week 40
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 (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Baseline was defined as Day 1 of the OLE Phase.
Time Frame
Baseline (OLE Phase), Through Week 40
Title
PC Phase: Maximum Plasma Concentration (Cmax) of VX-661 and IVA
Time Frame
Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85
Title
PC Phase: Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24h) of VX-661
Description
Pharmacokinetic (PK) sampling was performed up to 12 hours post-dose on Day 85. For Arm VX-661 50 mg q12h + IVA 150 mg q12h (VX-661 q12h regimen), area under the concentration versus time curve from time 0 to 12 hours (AUC0-12h) was multiplied by 2 to obtain AUC0-24h.
Time Frame
Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85
Title
PC Phase: Area Under the Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12h) of IVA
Time Frame
Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85
Title
PC Phase: Time to Reach Cmax (Tmax) of VX-661 and IVA
Time Frame
Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Homozygous for the F508del CFTR mutation
FEV1 ≥40% and ≤90% of predicted normal for age, sex, and height
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
Pregnant and nursing females: Females of childbearing potential must have a negative pregnancy test at screening and Day 1 of the PC Phase and Day -7 or Day 1 of the OLE Phase (whichever was applicable)
Sexually active participants of reproductive potential who are not willing to follow the contraception requirements
The participant or a close relative of the participant is the investigator or sub investigator, research assistant, pharmacist, study coordinator, or other staff directly involved with the conduct of the study.
Facility Information:
City
Birmingham
State/Province
Alabama
Country
United States
City
Palo Alto
State/Province
California
Country
United States
City
Stanford
State/Province
California
Country
United States
City
Altamonte Springs
State/Province
Florida
Country
United States
City
Miami
State/Province
Florida
Country
United States
City
Orlando
State/Province
Florida
Country
United States
City
Tampa
State/Province
Florida
Country
United States
City
Boise
State/Province
Idaho
Country
United States
City
Chicago
State/Province
Illinois
Country
United States
City
Boston
State/Province
Massachusetts
Country
United States
City
New Brunswick
State/Province
New Jersey
Country
United States
City
New York
State/Province
New York
Country
United States
City
Durham
State/Province
North Carolina
Country
United States
City
Cincinnati
State/Province
Ohio
Country
United States
City
Oklahoma City
State/Province
Oklahoma
Country
United States
City
Pittsburgh
State/Province
Pennsylvania
Country
United States
City
Charleston
State/Province
South Carolina
Country
United States
City
Memphis
State/Province
Tennessee
Country
United States
City
Houston
State/Province
Texas
Country
United States
City
Burlington
State/Province
Vermont
Country
United States
City
Colchester
State/Province
Vermont
Country
United States
City
Seattle
State/Province
Washington
Country
United States
City
Milwaukee
State/Province
Wisconsin
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Study to Evaluate Safety and Efficacy of VX-661 in Combination With Ivacaftor in Subjects With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation With an Open-Label Expansion
We'll reach out to this number within 24 hrs