Clinical trial NCT01707290: Rollover Study of Ivacaftor in Subjects With Cystic Fibrosis and a Non G551D CFTR Mutation
Official title: A Phase 3, Two-Arm, Rollover Study to Evaluate the Safety of Long Term Ivacaftor Treatment in Subjects 6 Years of Age and Older With Cystic Fibrosis and a Non-G551D 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: 2012-10-16
Enrollment: 125
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety of long-term ivacaftor treatment in participants with cystic fibrosis (CF) from Studies 110 (NCT01614457), 111 (NCT01614470), and 113 (NCT01685801).

Detailed description: Ivacaftor is the first Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulator to show an improvement in CFTR function and clinical benefit in participants with CF. Results from Phase 3 studies (NCT00909532 \[Study 102\] and NCT00909727 \[Study 103\]) showed that ivacaftor is effective in the treatment of participants 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 participants 6 years of age and older who have a G551D mutation in the CFTR gene.

Eligibility criteria: Inclusion Criteria:

* Participants from Study 110 or Study 111 entering the ivacaftor arm must have completed the assigned study drug treatment duration in the previous study.
* Participants from Study 113 entering the ivacaftor arm must have completed all study related treatments through the Follow-up Visit and met the Study 113 responder criteria during the previous study.
* Participants entering the observational arm must have completed at least 4 weeks of study drug treatment in their previous study (Study 110 or Study 111), must have completed the previous study but do not wish to enroll in the ivacaftor arm, or must have completed the previous study but do not meet the inclusion criteria of the ivacaftor arm.
* Participants of childbearing potential entering the ivacaftor arm must not be pregnant.
* Participants entering the ivacaftor arm must be willing to comply with contraception requirements.

Exclusion Criteria (Ivacaftor Arm Only):

* History of any illness or condition that might confound the results of the study or pose an additional risk in administering ivacaftor to the Participant.
* Use of moderate or strong inhibitors or inducers of cytochrome P450 (CYP) 3A.
* Evidence of cataract or lens opacity at or before the Day 1 Visit.

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) in Ivacaftor Arm
timeFrame: Day 1 up to Week 108 (Study 112)
Secondary outcomes:
measure: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 2, 12, 24, 36, 48, 60, 72, 84, 96, and 104
timeFrame: Baseline, Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104 (Study 112)
measure: Absolute Change From Baseline in Body Mass Index (BMI) at Week 2,12, 24, 36, 48, 60, 72, 84, 96 and 104
timeFrame: Baseline, Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104 (Study 112)
measure: Absolute Change From Baseline in Sweat Chloride at Week 2, 24, 48 and 104
timeFrame: Baseline, Week 2, 24, 48 and 104 (Study 112)
measure: Absolute Change From Baseline in Respiratory Domain of the Cystic Fibrosis Questionnaire Revised (CFQ-R) at Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104
timeFrame: Baseline, Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104 (Study 112)
measure: Number of Pulmonary Exacerbations Events
timeFrame: Through Week 104 (Study 112)
measure: Number of Participants With Serious Adverse Events (SAEs) in Observational Arm
timeFrame: up to 2 years (Study 112)
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Palo Alto
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Hartford
country: United States
state: Connecticut
city: Tampa
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
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: Ann Arbor
country: United States
state: Michigan
city: Detroit
country: United States
state: Michigan
city: Grand Rapids
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
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: Leuven
country: Belgium
city: Montpellier
country: France
city: Paris
country: France
city: Belfast
country: United Kingdom
city: Edinburgh
country: United Kingdom
Study officials:
affiliation: University of Pittsburgh
name: Joseph Pilewski, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pilewski JM, De Boeck K, Nick JA, Tian S, DeSouza C, Higgins M, Moss RB. Long-Term Ivacaftor in People Aged 6 Years and Older with Cystic Fibrosis with Ivacaftor-Responsive Mutations. Pulm Ther. 2020 Dec;6(2):303-313. doi: 10.1007/s41030-020-00129-2. Epub 2020 Sep 23.
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.