A Phase 2 Study to Evaluate Effects of VX-661/Ivacaftor on Lung and Extrapulmonary Systems in Subjects With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation
Primary Purpose
Cystic Fibrosis
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Tezacaftor/Ivacaftor
Ivacaftor
Tezacaftor/Ivacaftor matching placebo
Ivacaftor matching placebo
Sponsored by
About this trial
This is an interventional treatment trial for Cystic Fibrosis
Eligibility Criteria
Inclusion Criteria:
- Male and female participants, homozygous for the F508del CFTR mutation
- Confirmed diagnosis of CF by sweat chloride testing
- Forced Expiratory Volume in 1 Second (FEV1) ≥40% and ≤90% of predicted normal for age, sex, and height at Screening Visit
- 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 subject.
- An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 28 days before Day 1
- History or evidence of clinically significant findings on ophthalmologic examination during the Screening Period.
- History of solid organ or hematological transplantation
- Pregnant or nursing females
- Participants who have had radiation exposure within 1 year before the first mucociliary clearance (MCC) procedure that would cause them to exceed federal regulations by participating in this study
- In the opinion of the investigator, unable to adequately perform inhalation maneuvers during the MCC procedures
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Placebo
TEZ/IVA
Arm Description
Participants received placebo matched to tezacaftor (TEZ)/ivacaftor (IVA) fixed dose combination (FDC) tablet orally once daily in the morning followed by placebo matched to IVA tablet orally once daily in the evening for 29 days.
Participants received 100 milligram (mg) TEZ/150 mg IVA FDC tablet orally once daily in the morning followed by 150 mg IVA tablet orally once daily in the evening for 29 days.
Outcomes
Primary Outcome Measures
Absolute Change From Baseline in Mucociliary Clearance (MCC) at Day 28
MCC was assessed using an imaging technique that enables the tracking of mucus within the airways. MCC was expressed as the percentage of whole-lung clearance through 60 minutes at Baseline and Day 28.
Secondary Outcome Measures
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 28
Percent predicted FEV1 is the ratio of FEV1 to the predicted FEV1, expressed as a percentage. FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Absolute Change From Baseline in Small-bowel Area Under the Curve (AUC) Over 1-minute Mean pH Increments at Day 29
Absolute change from Baseline in small bowel AUC over 1-minute mean pH increments through 30 minutes at Day 29 was assessed.
Absolute Change From Baseline in Sweat Chloride at Day 29
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Full Information
NCT ID
NCT02508207
First Posted
July 23, 2015
Last Updated
June 28, 2021
Sponsor
Vertex Pharmaceuticals Incorporated
1. Study Identification
Unique Protocol Identification Number
NCT02508207
Brief Title
A Phase 2 Study to Evaluate Effects of VX-661/Ivacaftor on Lung and Extrapulmonary Systems in Subjects With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation
Official Title
A Phase 2, Randomized, Double-Blind, Placebo Controlled, Parallel-Group, Exploratory Study to Evaluate Effects of VX-661 in Combination With Ivacaftor on Lung and Extrapulmonary Systems in Subjects Aged 18 Years and Older With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation
Study Type
Interventional
2. Study Status
Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
February 2016 (undefined)
Primary Completion Date
June 2017 (Actual)
Study Completion Date
June 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vertex Pharmaceuticals Incorporated
4. Oversight
5. Study Description
Brief Summary
To evaluate the clinical mechanisms of action in lung and extrapulmonary systems of VX-661 (tezacaftor; TEZ) in combination with ivacaftor (IVA) (TEZ/IVA) in participants with cystic fibrosis (CF) who are homozygous for the F508del mutation on the CF transmembrane conductance regulator (CFTR) gene.
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 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
34 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received placebo matched to tezacaftor (TEZ)/ivacaftor (IVA) fixed dose combination (FDC) tablet orally once daily in the morning followed by placebo matched to IVA tablet orally once daily in the evening for 29 days.
Arm Title
TEZ/IVA
Arm Type
Experimental
Arm Description
Participants received 100 milligram (mg) TEZ/150 mg IVA FDC tablet orally once daily in the morning followed by 150 mg IVA tablet orally once daily in the evening for 29 days.
Intervention Type
Drug
Intervention Name(s)
Tezacaftor/Ivacaftor
Intervention Description
Tezacaftor/Ivacaftor FDC
Intervention Type
Drug
Intervention Name(s)
Ivacaftor
Intervention Type
Drug
Intervention Name(s)
Tezacaftor/Ivacaftor matching placebo
Intervention Type
Drug
Intervention Name(s)
Ivacaftor matching placebo
Primary Outcome Measure Information:
Title
Absolute Change From Baseline in Mucociliary Clearance (MCC) at Day 28
Description
MCC was assessed using an imaging technique that enables the tracking of mucus within the airways. MCC was expressed as the percentage of whole-lung clearance through 60 minutes at Baseline and Day 28.
Time Frame
Baseline, Day 28
Secondary Outcome Measure Information:
Title
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 28
Description
Percent predicted FEV1 is the ratio of FEV1 to the predicted FEV1, expressed as a percentage. FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time Frame
Baseline, Day 28
Title
Absolute Change From Baseline in Small-bowel Area Under the Curve (AUC) Over 1-minute Mean pH Increments at Day 29
Description
Absolute change from Baseline in small bowel AUC over 1-minute mean pH increments through 30 minutes at Day 29 was assessed.
Time Frame
Baseline, Day 29
Title
Absolute Change From Baseline in Sweat Chloride at Day 29
Time Frame
Baseline, Day 29
Title
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame
Baseline up to Day 57
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male and female participants, homozygous for the F508del CFTR mutation
Confirmed diagnosis of CF by sweat chloride testing
Forced Expiratory Volume in 1 Second (FEV1) ≥40% and ≤90% of predicted normal for age, sex, and height at Screening Visit
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 subject.
An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 28 days before Day 1
History or evidence of clinically significant findings on ophthalmologic examination during the Screening Period.
History of solid organ or hematological transplantation
Pregnant or nursing females
Participants who have had radiation exposure within 1 year before the first mucociliary clearance (MCC) procedure that would cause them to exceed federal regulations by participating in this study
In the opinion of the investigator, unable to adequately perform inhalation maneuvers during the MCC procedures
Facility Information:
City
Birmingham
State/Province
Alabama
Country
United States
City
Indianapolis
State/Province
Indiana
Country
United States
City
Baltimore
State/Province
Maryland
Country
United States
City
Chapel Hill
State/Province
North Carolina
Country
United States
City
Cincinnati
State/Province
Ohio
Country
United States
City
Toledo
State/Province
Ohio
Country
United States
City
Pittsburgh
State/Province
Pennsylvania
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Phase 2 Study to Evaluate Effects of VX-661/Ivacaftor on Lung and Extrapulmonary Systems in Subjects With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation
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