Back to resultsA Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of VX-661 in Combination With Ivacaftor
Primary Purpose
Cystic Fibrosis
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
VX-661 Plus Ivacaftor Combination
Ivacaftor
VX-661 Plus Ivacaftor Combination Placebo
Ivacaftor placebo
Sponsored by
About this trial
This is an interventional treatment trial for Cystic Fibrosis focused on measuring Homozygous for the F508del CFTR Mutation
Eligibility Criteria
Inclusion Criteria:
- Homozygous for the F508del CFTR mutation, genotype to be confirmed at the Screening Visit
- Confirmed diagnosis of CF defined as a sweat chloride value ≥60 mmol/L by quantitative pilocarpine iontophoresis
- Forced expiratory volume at one second (FEV1) ≥40% and ≤90% of predicted normal for age, sex, and height during screening
- Stable CF disease as judged by the investigator
- Willing to remain on a stable CF medication regimen through Week 24 or, if applicable, the Safety Follow up Visit
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, or changes in therapy (including antibiotics) for pulmonary disease within 28 days before Day 1 (first dose of study drug)
- Pregnant or nursing females (females of childbearing potential must have a negative pregnancy test at Screening and Day 1)
- 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 Type
Placebo Comparator
Experimental
Arm Label
Placebo
VX-661/IVA
Arm Description
Placebo matched to VX-661 plus IVA FDC tablet administered orally in the morning and placebo matched to IVA tablet administered orally in the evening up to Week 24.
VX-661 100 mg plus IVA 150 mg FDC tablet administered orally in the morning and IVA 150 mg tablet administered orally in the evening up to Week 24.
Outcomes
Primary Outcome Measures
Absolute Change From Baseline (Day 1) in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 24
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Secondary Outcome Measures
Relative Change From Baseline (Day 1) in ppFEV1 Through Week 24
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Number of Pulmonary Exacerbations Per Year
Pulmonary exacerbation was defined as a new event or change in antibiotic therapy for greater than or equal to 4 sinopulmonary signs/symptoms. Pulmonary exacerbation events per year (48 weeks) were reported.
Absolute Change From Baseline (Day 1) Body Mass Index (BMI) at Week 24
BMI was defined as weight in kilograms (kg) divided by height in square meter (m^2).
Absolute Change From Baseline (Day 1) in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 24
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.
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. Any AE that increased in severity or newly developed at or after initial dosing of study drug to Week 28 was considered treatment-emergent.
Number of Participants With at Least One Pulmonary Exacerbation Pulmonary Exacerbation Through Week 24
Pulmonary exacerbation was defined as a new event or change in antibiotic therapy for greater than or equal to 4 sinopulmonary signs/symptoms. Time to event data was not collected and instead, Number of Subjects with first event were collected and are reported. Time-to-first pulmonary exacerbation was planned to be estimated using Kaplan-Meier (KM) estimates. However, due to less than 50% of events, time-to-first event data was not estimated. Instead, number of participants with at least one pulmonary exacerbation event were collected and are reported.
Absolute Change From Baseline (Day 1) in Sweat Chloride Through Week 24
Sweat samples were collected using an approved collection device.
Absolute Change From Baseline (Day 1) in BMI Z-score at Week 24 in Participants Less Than (<) 20 Years Old at the Time of Screening)
BMI was defined as weight in kg divided by height in m^2. z-score is a statistical measure to describe whether a mean was above or below the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score (BMI z-score).
Absolute Change From Baseline (Day 1) in Body Weight at Week 24
Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1 VX-661 and M2-VX-661), Ivacaftor (IVA) and IVA Metabolite (M1-IVA)
This outcome was not planned to be assessed in Placebo arm.
Full Information
NCT ID
NCT02347657
First Posted
January 12, 2015
Last Updated
May 8, 2018
Sponsor
Vertex Pharmaceuticals Incorporated
1. Study Identification
Unique Protocol Identification Number
NCT02347657
Brief Title
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of VX-661 in Combination With Ivacaftor
Official Title
A Phase 3, Randomized, Double Blind, Placebo Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Homozygous for the F508del CFTR Mutation
Study Type
Interventional
2. Study Status
Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
January 2015 (Actual)
Primary Completion Date
January 20, 2017 (Actual)
Study Completion Date
January 20, 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
This is a Phase 3, randomized, double blind, placebo controlled, parallel group, multicenter study in people with cystic fibrosis (CF) who are homozygous for the F508del CF transmembrane conductance regulator (CFTR) gene mutation.
Detailed Description
This is a Phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter study in people with CF who are homozygous for the F508del-CFTR mutation. This study is designed to evaluate the efficacy and safety of VX-661 in combination with Ivacaftor (IVA, VX-770). The active treatment regimen comprised of a morning dose of a fixed-dose combination (FDC) tablet of 100 milligram (mg) VX-661/150 mg IVA once daily (qd) and an evening dose of IVA 150 mg to be taken approximately 12 hours after the morning dose. The placebo regimen was visually matched tablets to be taken with the same schedule as the active treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
Keywords
Homozygous for the F508del CFTR Mutation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
510 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo matched to VX-661 plus IVA FDC tablet administered orally in the morning and placebo matched to IVA tablet administered orally in the evening up to Week 24.
Arm Title
VX-661/IVA
Arm Type
Experimental
Arm Description
VX-661 100 mg plus IVA 150 mg FDC tablet administered orally in the morning and IVA 150 mg tablet administered orally in the evening up to Week 24.
Intervention Type
Drug
Intervention Name(s)
VX-661 Plus Ivacaftor Combination
Intervention Description
FDC tablet, oral use
Intervention Type
Drug
Intervention Name(s)
Ivacaftor
Intervention Description
Tablet, oral use
Intervention Type
Drug
Intervention Name(s)
VX-661 Plus Ivacaftor Combination Placebo
Intervention Description
FDC tablet, oral use
Intervention Type
Drug
Intervention Name(s)
Ivacaftor placebo
Intervention Description
Tablet, oral use
Primary Outcome Measure Information:
Title
Absolute Change From Baseline (Day 1) in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 24
Description
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time Frame
Day 1, Through Week 24
Secondary Outcome Measure Information:
Title
Relative Change From Baseline (Day 1) in ppFEV1 Through Week 24
Description
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time Frame
Day 1, Through Week 24
Title
Number of Pulmonary Exacerbations Per Year
Description
Pulmonary exacerbation was defined as a new event or change in antibiotic therapy for greater than or equal to 4 sinopulmonary signs/symptoms. Pulmonary exacerbation events per year (48 weeks) were reported.
Time Frame
Day 1 through Week 24
Title
Absolute Change From Baseline (Day 1) Body Mass Index (BMI) at Week 24
Description
BMI was defined as weight in kilograms (kg) divided by height in square meter (m^2).
Time Frame
Day 1, Week 24
Title
Absolute Change From Baseline (Day 1) in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 24
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
Day 1, Through Week 24
Title
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. Any AE that increased in severity or newly developed at or after initial dosing of study drug to Week 28 was considered treatment-emergent.
Time Frame
Day 1 up to Week 28
Title
Number of Participants With at Least One Pulmonary Exacerbation Pulmonary Exacerbation Through Week 24
Description
Pulmonary exacerbation was defined as a new event or change in antibiotic therapy for greater than or equal to 4 sinopulmonary signs/symptoms. Time to event data was not collected and instead, Number of Subjects with first event were collected and are reported. Time-to-first pulmonary exacerbation was planned to be estimated using Kaplan-Meier (KM) estimates. However, due to less than 50% of events, time-to-first event data was not estimated. Instead, number of participants with at least one pulmonary exacerbation event were collected and are reported.
Time Frame
Day 1 through Week 24
Title
Absolute Change From Baseline (Day 1) in Sweat Chloride Through Week 24
Description
Sweat samples were collected using an approved collection device.
Time Frame
Day 1, Through Week 24
Title
Absolute Change From Baseline (Day 1) in BMI Z-score at Week 24 in Participants Less Than (<) 20 Years Old at the Time of Screening)
Description
BMI was defined as weight in kg divided by height in m^2. z-score is a statistical measure to describe whether a mean was above or below the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score (BMI z-score).
Time Frame
Day 1, Week 24
Title
Absolute Change From Baseline (Day 1) in Body Weight at Week 24
Time Frame
Day 1, Week 24
Title
Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1 VX-661 and M2-VX-661), Ivacaftor (IVA) and IVA Metabolite (M1-IVA)
Description
This outcome was not planned to be assessed in Placebo arm.
Time Frame
Pre-morning dose on Week 16
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Homozygous for the F508del CFTR mutation, genotype to be confirmed at the Screening Visit
Confirmed diagnosis of CF defined as a sweat chloride value ≥60 mmol/L by quantitative pilocarpine iontophoresis
Forced expiratory volume at one second (FEV1) ≥40% and ≤90% of predicted normal for age, sex, and height during screening
Stable CF disease as judged by the investigator
Willing to remain on a stable CF medication regimen through Week 24 or, if applicable, the Safety Follow up Visit
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, or changes in therapy (including antibiotics) for pulmonary disease within 28 days before Day 1 (first dose of study drug)
Pregnant or nursing females (females of childbearing potential must have a negative pregnancy test at Screening and Day 1)
Sexually active participants of reproductive potential who are not willing to follow the contraception requirements
Facility Information:
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Little Rock
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Bordeaux
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Paris cedex 14
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Paris
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Paris Cedex 19
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Paris
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Rhone
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Heidelberg
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Germany
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Birmingham
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Belfast
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London
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United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
29099344
Citation
Taylor-Cousar JL, Munck A, McKone EF, van der Ent CK, Moeller A, Simard C, Wang LT, Ingenito EP, McKee C, Lu Y, Lekstrom-Himes J, Elborn JS. Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del. N Engl J Med. 2017 Nov 23;377(21):2013-2023. doi: 10.1056/NEJMoa1709846. Epub 2017 Nov 3.
Results Reference
derived
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A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of VX-661 in Combination With Ivacaftor
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