Clinical trial NCT01614470: Study of Ivacaftor in Subjects With Cystic Fibrosis (CF) Who Have a Non-G551D CF Transmembrane Conductance Regulator (CFTR) Gating Mutation
Official title: A Phase 3, Two-Part, Randomized, Double-Blind, Placebo-Controlled, Crossover Study With an Open-Label Period to Evaluate the Efficacy and Safety of Ivacaftor in Subjects With Cystic Fibrosis Who Have a Non-G551D CFTR Gating Mutation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
Collaborators: name: Cystic Fibrosis Foundation
First posted: 2012-06-08
Enrollment: 39
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of ivacaftor in subjects with cystic fibrosis (CF) who have a non-G551D cystic fibrosis transmembrane regulator (CFTR) gating mutation (any one of the following CFTR mutations: G178R, G551S, S549N, S549R, G970R, G1244E, S1251N, S1255P, or G1349D).

Detailed description: Ivacaftor is the first CFTR modulator to show an improvement in CFTR function and clinical benefit in subjects with CF. Results from Phase 3 studies (VX08-770-102 \[Study 102\] \[NCT00909532\] and VX08-770-103 \[Study 103\] \[NCT00909727\]) showed that ivacaftor is effective in the treatment of subjects with CF who have the G551D-CFTR mutation, as evidenced by sustained improvements in CFTR channel function (measured by reduction in sweat chloride concentration) and corresponding substantial, durable improvements in lung function, pulmonary exacerbations, respiratory symptoms, and weight gain. Ivacaftor was also well tolerated, as evidenced by the rates and reasons for premature discontinuation and results of safety assessments.

Ivacaftor (Trade Name Kalydeco; 150 mg tablets) was initially approved in the United States for the treatment of CF in subjects 6 years of age and older who have a G551D mutation in the CFTR gene.

Eligibility criteria: Inclusion Criteria:

* Male or female with confirmed diagnosis of CF
* At least 1 allele of the following CFTR gating mutations: G178R, S549N, S549R, G551S, G970R, G1244E, S1251N, S1255P, G1349D
* Percent predicted forced expiratory volume in 1 second (FEV1) greater than or equal to (\>=) 40 percent (%) predicted normal for age, sex, and height
* 6 years of age or older
* Minimum weight of 15 kilogram (kg) at screening
* Females of childbearing potential must not be pregnant
* Willing to comply with contraception requirements

Exclusion Criteria:

* G551D-CFTR mutation on at least 1 allele
* History of any illness or condition that might confound the results of the study or pose an additional risk in administering ivacaftor to the subject
* An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before the first dose of study drug
* History of solid organ or hematological transplantation
* History of alcohol, medication or illicit drug abuse within 1 year before the first dose of study drug
* Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within 30 days before screening
* Use of inhaled hypertonic saline treatment
* Use of any inhibitors or inducers of cytochrome (CYP) P450 3A
* Evidence of cataract or lens opacity at screening

Primary outcomes:
measure: Part 1: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8
timeFrame: Part 1: Baseline (pre-dose Day 1), Week 8
measure: Part 2: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through 24 Weeks of Treatment (Week 36 Visit)
timeFrame: Baseline (pre-dose Week 12), Week 36
Secondary outcomes:
measure: Part 1: Change From Baseline in Body Mass Index (BMI) at Week 8
timeFrame: Part 1: Baseline (pre-dose Day 1), Week 8
measure: Part 2: Change From Baseline in Body Mass Index (BMI) at 24 Weeks of Treatment (Week 36 Visit)
timeFrame: Baseline (pre-dose Week 12), Week 36
measure: Part 1: Change From Baseline in Sweat Chloride Through Week 8
timeFrame: Part 1: Baseline (pre-dose Day 1), Week 8
measure: Part 2: Change From Baseline in Sweat Chloride Through 24 Weeks of Treatment (Week 36 Visit)
timeFrame: Baseline (pre-dose Week 12), Week 36
measure: Part 1: Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 8
timeFrame: Part 1: Baseline (pre-dose Day 1), Week 8
measure: Part 2: Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through 24 Weeks of Treatment (Week 36 Visit)
timeFrame: Baseline (pre-dose Week 12), Week 36
measure: Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Part 1: From signing of informed consent up to Week 20
measure: Part 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Part 2: Week 20 up to Week 40
Other outcomes:
Locations:
city: Tampa
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Boston
country: United States
state: Massachusetts
city: Ann Arbor
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
city: St. Louis
country: United States
state: Missouri
city: Houston
country: United States
state: Texas
city: Leuven
country: Belgium
city: Lyon
country: France
city: Montpellier
country: France
city: Paris
country: France
Study officials:
affiliation: University of Leuven
name: Christine De Boeck, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: