Clinical trial NCT01946412: Roll-Over Study of Ivacaftor in Cystic Fibrosis Pediatric Subjects With a CF Transmembrane Conductance Regulator Gene (CFTR) Gating Mutation
Official title: A Phase 3, 2-Arm, Roll-Over Study to Evaluate the Long-term Safety and Pharmacodynamics of Ivacaftor Treatment in Pediatric Subjects With Cystic Fibrosis and a CFTR Gating Mutation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Keywords: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
Collaborators: name: Cystic Fibrosis Foundation
First posted: 2013-09-19
Enrollment: 33
Sex: ALL
Minimum age (years): 2
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 provide information regarding the long-term safety and pharmacodynamics of ivacaftor treatment in the pediatric population younger than 6 years of age with Cystic Fibrosis (CF) who have a CFTR gating mutation in at least 1 allele and will further explore the efficacy of long-term ivacaftor treatment in this population of patients with CF.


Eligibility criteria: Inclusion Criteria (Ivacaftor Arm):

1. Completed the last study visit of the treatment period of the previous study (NCT01705145)
2. Hematology, serum chemistry, and vital signs results on Day 1 with no clinically significant abnormalities that would interfere with the study assessments, as judged by the investigator
3. As judged by the investigator, parent or legal guardian must be able to understand protocol requirements, restrictions, and instructions and the parent or legal guardian should be able to ensure that the subject assents to participation in the study to the degree the subject can assent, and that the subject will comply with and is likely to complete the study as planned

Inclusion Criteria (Observational Arm):

1. Subjects who completed their assigned study drug treatment in the previous study (NCT01705145) and elected not to enroll in the ivacaftor arm and subjects who prematurely discontinued treatment in the previous study and received at least 1 dose of study drug treatment in the previous study will be eligible for enrollment in the observational arm.

Exclusion Criteria (Ivacaftor Arm):

1. Subjects who prematurely discontinued from the previous study
2. History of any illness or condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject
3. Subjects with a history of study treatment intolerance as observed in their previous study that, in the opinion of the investigator, might pose an additional risk in administering study drug to the subject
4. Subjects receiving commercially-available ivacaftor treatment
5. Subject was unable to complete an adequate slit-lamp examination at the last ophthalmologic examination in the previous study

Exclusion Criteria: (Observational Arm)

1. Subjects receiving ivacaftor treatment will not be eligible for enrollment in the observational arm.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 up to Week 97 (for participants who completed study drug dosing); Day 1 up to 24 weeks after the last dose (up to Week 108, for participants who prematurely discontinued study drug dosing)
Secondary outcomes:
measure: Absolute Change From Baseline of Parent Study in Sweat Chloride at Week 24, 48, 72 and 84
timeFrame: Baseline (study 108), Week 24, 48, 72 and 84 (study 109)
measure: Absolute Change From Baseline of Study 109 in Sweat Chloride at Week 24, 48, 72 and 84
timeFrame: Baseline (study 109), Week 24, 48, 72 and 84 (study 109)
measure: Absolute Change From Baseline of Parent Study in Weight at Week 12, 24, 36, 48, 60, 72 and 84
timeFrame: Baseline (study 108), Week 12, 24, 36, 48, 60, 72 and 84 (study 109)
measure: Absolute Change From Baseline of Study 109 in Weight at Week 12, 24, 36, 48, 60, 72 and 84
timeFrame: Baseline (study 109), Week 12, 24, 36, 48, 60, 72 and 84 (study 109)
measure: Absolute Change From Baseline of Parent Study in Stature at Week 12, 24, 36, 48, 60, 72 and 84
timeFrame: Baseline (study 108), Week 12, 24, 36, 48, 60, 72 and 84 (study 109)
measure: Absolute Change From Baseline of Study 109 in Stature at Week 12, 24, 36, 48, 60, 72 and 84
timeFrame: Baseline (study 109), Week 12, 24, 36, 48, 60, 72 and 84 (study 109)
measure: Absolute Change From Baseline of Parent Study in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84
timeFrame: Baseline (study 108), Week 12, 24, 36, 48, 60, 72 and 84 (study 109)
measure: Absolute Change From Baseline of Study 109 in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84
timeFrame: Baseline (study 109), Week 12, 24, 36, 48, 60, 72 and 84 (study 109)
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Denver
country: United States
state: Colorado
city: Atlanta
country: United States
state: Georgia
city: Indianapolis
country: United States
state: Indiana
city: Boston
country: United States
state: Massachusetts
city: Grand Rapids
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
city: Kansas city
country: United States
state: Missouri
city: Omaha
country: United States
state: Nebraska
city: Salt Lake City
country: United States
state: Utah
city: Richmond
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Vancouver
country: Canada
state: British Columbia
city: Edinburgh
country: United Kingdom
city: Liverpool
country: United Kingdom
city: London
country: United Kingdom
Study officials:
affiliation: Vertex Pharmaceuticals Incorporated
name: Adebayo Lawal, M.D.
role: STUDY_DIRECTOR
References:
citation: Rosenfeld M, Cunningham S, Harris WT, Lapey A, Regelmann WE, Sawicki GS, Southern KW, Chilvers M, Higgins M, Tian S, Cooke J, Davies JC; KLIMB study group. An open-label extension study of ivacaftor in children with CF and a CFTR gating mutation initiating treatment at age 2-5 years (KLIMB). J Cyst Fibros. 2019 Nov;18(6):838-843. doi: 10.1016/j.jcf.2019.03.009. Epub 2019 Apr 30.