Clinical trial NCT00865904: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Keywords: ∆F508
F508del
Cystic Fibrosis Transmembrane Conductance Regulator
CFTR
Pancreatic diseases
Lung diseases
Genetic disease, inborn
Infant, newborn, diseases
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2009-03-19
Enrollment: 93
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Safety and Tolerability Based on Adverse Events (AEs)
timeFrame: Up to 14 days after last dose (last dose = Day 28)
Secondary outcomes:
measure: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Day 28
timeFrame: Baseline, Day 28
measure: Change From Baseline in Percent Predicted FEV1 at Day 28
timeFrame: Baseline, Day 28
measure: Change From Baseline in Forced Vital Capacity (FVC) at Day 28
timeFrame: Baseline, Day 28
measure: Change From Baseline in Forced Expiratory Flow Over the Middle Half of the FVC (FEF25-75) at Day 28
timeFrame: Baseline, Day 28
measure: Change From Baseline in Sweat Chloride at Day 28
timeFrame: Baseline, Day 28
measure: Change From Baseline in Nasal Potential Difference (NPD) of Zero Chloride Plus Isoproterenol Response at Day 28
timeFrame: Baseline, Day 28
measure: Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28
timeFrame: Baseline, Day 28
measure: Maximum Plasma Concentration (Cmax) of VX-809
timeFrame: 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)
measure: Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of VX-809
timeFrame: 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)
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Palo Alto
country: United States
state: California
city: San Diego
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Iowa City
country: United States
state: Iowa
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Minneapolis
country: United States
state: Minnesota
city: St. Louis
country: United States
state: Missouri
city: Chapel Hill
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Seattle
country: United States
state: Washington
city: Brussels
country: Belgium
city: Leuven
country: Belgium
city: Toronto
country: Canada
state: Ontario
city: Cologne
country: Germany
city: Hannover
country: Germany
city: Rotterdam
country: Netherlands
city: Utrecht
country: Netherlands
Study officials:
affiliation: Vertex Pharmaceuticals Incorporated
name: Medical Monitor
role: STUDY_DIRECTOR
References:
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.
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.