Back to resultsStudy of VX-809 in Cystic Fibrosis Subjects With the ∆F508-CFTR Gene Mutation
Primary Purpose
Cystic Fibrosis
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
VX-809
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Cystic Fibrosis focused on measuring ∆F508, F508del, Cystic Fibrosis Transmembrane Conductance Regulator, CFTR, Pancreatic diseases, Lung diseases, Genetic disease, inborn, Infant, newborn, diseases
Eligibility Criteria
Inclusion Criteria:
- Confirmed diagnosis of CF with ∆F508-CFTR mutation in both alleles
- Forced expiratory volume in 1 second (FEV1) greater than or equal to (>=) 40 percent (%) of predicted normal for age, gender, and height
- Weight >=40 kilograms (kg) and body mass index greater than or equal to 18.5 kilogram per square meter (kg/m^2)
- Screening laboratory values, tests, and physical examination within acceptable ranges
- Negative pregnancy test (for women of child-bearing potential)
- Able and willing to follow contraceptive requirements
- Willing to remain on a stable medication regimen for the duration of study participation
Exclusion Criteria:
- History of any illness, or any ongoing acute illness, that could impact the safety of the study participant or may confound results of study
- Pulmonary exacerbation or changes in therapy for pulmonary disease within 14 days before receiving the first dose of study drug
- Impaired hepatic or renal function
- History of organ or hematological transplant
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Placebo Comparator
Experimental
Experimental
Experimental
Experimental
Arm Label
Placebo
VX-809, 25 mg
VX-809, 50 mg
VX-809, 100 mg
VX-809, 200 mg
Arm Description
Placebo matched to VX-809 capsule orally once daily for 28 days.
VX-809, 25 milligram (mg) capsule orally once daily for 28 days.
VX-809, 50 mg capsule orally once daily for 28 days.
VX-809, 100 mg capsule orally once daily for 28 days.
VX-809, 200 mg capsule orally once daily for 28 days.
Outcomes
Primary Outcome Measures
Safety and Tolerability Based on Adverse Events (AEs)
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. Serious adverse event (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, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Number of participants with AEs and SAEs are reported. An AE that started at or after initial dosing of study drug, or increased in severity after initial dosing of study drug visit is considered treatment-emergent.
Secondary Outcome Measures
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Day 28
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Change From Baseline in Percent Predicted FEV1 at Day 28
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Predicted FEV1 (for age, gender, and height) was calculated using the Knudson method.
Change From Baseline in Forced Vital Capacity (FVC) at Day 28
FVC is the volume of air that can be forcibly exhaled from the lungs after taking the deepest breath possible.
Change From Baseline in Forced Expiratory Flow Over the Middle Half of the FVC (FEF25-75) at Day 28
FEF25-75 is total volume of air exhaled from the lungs over the middle half of the FVC test, expressed as liters per second (L/sec).
Change From Baseline in Sweat Chloride at Day 28
Sweat samples were collected using an approved Macroduct (Wescor) collection device. A volume of greater than or equal to (>=) 15 microliter was required for determination of sweat chloride.
Change From Baseline in Nasal Potential Difference (NPD) of Zero Chloride Plus Isoproterenol Response at Day 28
Nasal potential difference (NPD) provides a direct and sensitive evaluation of sodium and chloride transport in secretory epithelial cells via assessment of transepithelial bioelectric properties. NPD under conditions of zero chloride concentration perfusion solution in the presence of isoproterenol is reported.
NPDs were performed according to Cystic Fibrosis Foundation Therapeutics Development Network (CFFT TDN) Standard Operating Procedure (SOP) 528.00 "Standardization of Measurement of Nasal Membrane Transepithelial Potential Difference (NPD) - electronic data capture (EDC) and Perfusion or Perfusion-Free Probe".
Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. CFQ-R domains include: Body, Digestion, Eat, Emotion, Health Perceptions, Physical, Respiratory, Role, Social, Treatment Burden, Vitality, and Weight. Individual domain score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Maximum Plasma Concentration (Cmax) of VX-809
Only participants who received VX-809 were analyzed for this outcome measure.
Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of VX-809
Only participants who received VX-809 were analyzed for this outcome measure.
Full Information
NCT ID
NCT00865904
First Posted
March 18, 2009
Last Updated
August 1, 2015
Sponsor
Vertex Pharmaceuticals Incorporated
1. Study Identification
Unique Protocol Identification Number
NCT00865904
Brief Title
Study of VX-809 in Cystic Fibrosis Subjects With the ∆F508-CFTR Gene Mutation
Official Title
A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study of VX-809 to Evaluate Safety, Pharmacokinetics, and Pharmacodynamics of VX-809 in Cystic Fibrosis Subjects Homozygous for the ∆F508-CFTR Gene Mutation
Study Type
Interventional
2. Study Status
Record Verification Date
June 2015
Overall Recruitment Status
Completed
Study Start Date
March 2009 (undefined)
Primary Completion Date
December 2009 (Actual)
Study Completion Date
December 2009 (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 primary objective of the study was to evaluate the safety and tolerability of VX-809 in participants with cystic fibrosis (CF) who are homozygous for the F508del mutation on the CF transmembrane conductance regulator (CFTR) gene.
Detailed Description
This was a Phase 2, randomized, double-blind, placebo-controlled, multiple-dose study of orally-administered VX-809 in participants with CF who are homozygous for the specific CFTR mutation known as ∆F508 or F508del. Enrollment was planned for 90 participants at approximately 20 centers. Participants were planned to be randomized in a 4:1 ratio to receive 1 of 4 doses of VX-809 or placebo once a day for 28 days in a parallel design. Participants were outpatients during the study, except for overnight stays on Day 1 and 28.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
Keywords
∆F508, F508del, Cystic Fibrosis Transmembrane Conductance Regulator, CFTR, Pancreatic diseases, Lung diseases, Genetic disease, inborn, Infant, newborn, diseases
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
93 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo matched to VX-809 capsule orally once daily for 28 days.
Arm Title
VX-809, 25 mg
Arm Type
Experimental
Arm Description
VX-809, 25 milligram (mg) capsule orally once daily for 28 days.
Arm Title
VX-809, 50 mg
Arm Type
Experimental
Arm Description
VX-809, 50 mg capsule orally once daily for 28 days.
Arm Title
VX-809, 100 mg
Arm Type
Experimental
Arm Description
VX-809, 100 mg capsule orally once daily for 28 days.
Arm Title
VX-809, 200 mg
Arm Type
Experimental
Arm Description
VX-809, 200 mg capsule orally once daily for 28 days.
Intervention Type
Drug
Intervention Name(s)
VX-809
Intervention Description
Capsules
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo matched to VX-809 capsules.
Primary Outcome Measure Information:
Title
Safety and Tolerability Based on Adverse Events (AEs)
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. Serious adverse event (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, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Number of participants with AEs and SAEs are reported. An AE that started at or after initial dosing of study drug, or increased in severity after initial dosing of study drug visit is considered treatment-emergent.
Time Frame
Up to 14 days after last dose (last dose = Day 28)
Secondary Outcome Measure Information:
Title
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Day 28
Description
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time Frame
Baseline, Day 28
Title
Change From Baseline in Percent Predicted FEV1 at Day 28
Description
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Predicted FEV1 (for age, gender, and height) was calculated using the Knudson method.
Time Frame
Baseline, Day 28
Title
Change From Baseline in Forced Vital Capacity (FVC) at Day 28
Description
FVC is the volume of air that can be forcibly exhaled from the lungs after taking the deepest breath possible.
Time Frame
Baseline, Day 28
Title
Change From Baseline in Forced Expiratory Flow Over the Middle Half of the FVC (FEF25-75) at Day 28
Description
FEF25-75 is total volume of air exhaled from the lungs over the middle half of the FVC test, expressed as liters per second (L/sec).
Time Frame
Baseline, Day 28
Title
Change From Baseline in Sweat Chloride at Day 28
Description
Sweat samples were collected using an approved Macroduct (Wescor) collection device. A volume of greater than or equal to (>=) 15 microliter was required for determination of sweat chloride.
Time Frame
Baseline, Day 28
Title
Change From Baseline in Nasal Potential Difference (NPD) of Zero Chloride Plus Isoproterenol Response at Day 28
Description
Nasal potential difference (NPD) provides a direct and sensitive evaluation of sodium and chloride transport in secretory epithelial cells via assessment of transepithelial bioelectric properties. NPD under conditions of zero chloride concentration perfusion solution in the presence of isoproterenol is reported.
NPDs were performed according to Cystic Fibrosis Foundation Therapeutics Development Network (CFFT TDN) Standard Operating Procedure (SOP) 528.00 "Standardization of Measurement of Nasal Membrane Transepithelial Potential Difference (NPD) - electronic data capture (EDC) and Perfusion or Perfusion-Free Probe".
Time Frame
Baseline, Day 28
Title
Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28
Description
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. CFQ-R domains include: Body, Digestion, Eat, Emotion, Health Perceptions, Physical, Respiratory, Role, Social, Treatment Burden, Vitality, and Weight. Individual domain score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Time Frame
Baseline, Day 28
Title
Maximum Plasma Concentration (Cmax) of VX-809
Description
Only participants who received VX-809 were analyzed for this outcome measure.
Time Frame
Day 1 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, and 24 hours post-dose), Day 28 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, 24, and 30-60 hours post dose)
Title
Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of VX-809
Description
Only participants who received VX-809 were analyzed for this outcome measure.
Time Frame
Day 1 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, and 24 hours post-dose), Day 28 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, and 24 hours post dose)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Confirmed diagnosis of CF with ∆F508-CFTR mutation in both alleles
Forced expiratory volume in 1 second (FEV1) greater than or equal to (>=) 40 percent (%) of predicted normal for age, gender, and height
Weight >=40 kilograms (kg) and body mass index greater than or equal to 18.5 kilogram per square meter (kg/m^2)
Screening laboratory values, tests, and physical examination within acceptable ranges
Negative pregnancy test (for women of child-bearing potential)
Able and willing to follow contraceptive requirements
Willing to remain on a stable medication regimen for the duration of study participation
Exclusion Criteria:
History of any illness, or any ongoing acute illness, that could impact the safety of the study participant or may confound results of study
Pulmonary exacerbation or changes in therapy for pulmonary disease within 14 days before receiving the first dose of study drug
Impaired hepatic or renal function
History of organ or hematological transplant
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Vertex Pharmaceuticals Incorporated
Official's Role
Study Director
Facility Information:
City
Birmingham
State/Province
Alabama
Country
United States
City
Palo Alto
State/Province
California
Country
United States
City
San Diego
State/Province
California
Country
United States
City
Aurora
State/Province
Colorado
Country
United States
City
Atlanta
State/Province
Georgia
Country
United States
City
Chicago
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
Minneapolis
State/Province
Minnesota
Country
United States
City
St. Louis
State/Province
Missouri
Country
United States
City
Chapel Hill
State/Province
North Carolina
Country
United States
City
Cincinnati
State/Province
Ohio
Country
United States
City
Cleveland
State/Province
Ohio
Country
United States
City
Columbus
State/Province
Ohio
Country
United States
City
Philadelphia
State/Province
Pennsylvania
Country
United States
City
Pittsburgh
State/Province
Pennsylvania
Country
United States
City
Seattle
State/Province
Washington
Country
United States
City
Brussels
Country
Belgium
City
Leuven
Country
Belgium
City
Toronto
State/Province
Ontario
Country
Canada
City
Cologne
Country
Germany
City
Hannover
Country
Germany
City
Rotterdam
Country
Netherlands
City
Utrecht
Country
Netherlands
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
21825083
Citation
Clancy JP, Rowe SM, Accurso FJ, Aitken ML, Amin RS, Ashlock MA, Ballmann M, Boyle MP, Bronsveld I, Campbell PW, De Boeck K, Donaldson SH, Dorkin HL, Dunitz JM, Durie PR, Jain M, Leonard A, McCoy KS, Moss RB, Pilewski JM, Rosenbluth DB, Rubenstein RC, Schechter MS, Botfield M, Ordonez CL, Spencer-Green GT, Vernillet L, Wisseh S, Yen K, Konstan MW. Results of a phase IIa study of VX-809, an investigational CFTR corrector compound, in subjects with cystic fibrosis homozygous for the F508del-CFTR mutation. Thorax. 2012 Jan;67(1):12-8. doi: 10.1136/thoraxjnl-2011-200393. Epub 2011 Aug 8.
Results Reference
derived
Learn more about this trial
Study of VX-809 in Cystic Fibrosis Subjects With the ∆F508-CFTR Gene Mutation
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