Clinical trial NCT01614457: Study of Ivacaftor in Subjects With Cystic Fibrosis (CF) Who Have the R117H-CF Transmembrane Conductance Regulator (CFTR) Mutation (KONDUCT)
Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Ivacaftor in Subjects With Cystic Fibrosis Who Have the R117H-CFTR 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: 70
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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 the R117H-CFTR mutation.

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
* Must have at least 1 allele of the R117H CFTR mutation
* Percent predicted forced expiratory volume in 1 second (FEV1) 40 percent (%) to 90% (for subjects aged 12 years or older) or 40% to 105% (for subjects aged 6 to 11 years) 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:

* CFTR gene mutation leading to CFTR channel with gating defect (that is, any 1 of the following mutations: G551D, G178R, G551S, S549N, S549R, G970R, G1244E, S1251N, S1255P, or G1349D)
* 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
* Abnormal liver function, at screening, defined as greater than or equal to (\>=) 3 time upper limit of normal (ULN), of any 3 or more of the following: serum aspartate transaminase (AST), serum alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT), serum alkaline phosphatase (ALP), total bilirubin
* Colonization with organisms associated with a more rapid decline in pulmonary status (for example, Burkholderia cenocepacia, Burkholderia dolosa, and Mycobacterium abscessus) at screening
* 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
* Any "non-CF-related" illness within 2 weeks before Day 1 (first dose of study drug). "Illness" was defined as an acute (serious or non-serious) condition (for example, gastroenteritis)
* Use of any inhibitors or inducers of cytochrome (CYP) P450 3A

Primary outcomes:
measure: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 24
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Change From Baseline in Body Mass Index (BMI) at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Sweat Chloride Through Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 24
timeFrame: Baseline, Week 24
measure: Time to First Pulmonary Exacerbation
timeFrame: Day 0 to 15, Day 16 to 56, Day 57 to 112, Day 113 to 168
measure: Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to follow-up (3 to 4 weeks after last dose [last dose = Week 24])
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Palo Alto
country: United States
state: California
city: Hartford
country: United States
state: Connecticut
city: Tampa
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Iowa City
country: United States
state: Iowa
city: Lexington
country: United States
state: Kentucky
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Grand Rapids
country: United States
state: Michigan
city: St. Louis
country: United States
state: Missouri
city: Omaha
country: United States
state: Nebraska
city: New York
country: United States
state: New York
city: Syracuse
country: United States
state: New York
city: Valhalla
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Nashville
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Richmond
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Morgantown
country: United States
state: West Virginia
city: Madison
country: United States
state: Wisconsin
city: Belfast
country: United Kingdom
city: Edinburgh
country: United Kingdom
Study officials:
affiliation: Stanford University
name: Richard Moss, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Moss RB, Flume PA, Elborn JS, Cooke J, Rowe SM, McColley SA, Rubenstein RC, Higgins M; VX11-770-110 (KONDUCT) Study Group. Efficacy and safety of ivacaftor in patients with cystic fibrosis who have an Arg117His-CFTR mutation: a double-blind, randomised controlled trial. Lancet Respir Med. 2015 Jul;3(7):524-33. doi: 10.1016/S2213-2600(15)00201-5. Epub 2015 Jun 9.