search
Back to results

Roll-Over Study of Ivacaftor in Cystic Fibrosis Pediatric Subjects With a CF Transmembrane Conductance Regulator Gene (CFTR) Gating Mutation

Primary Purpose

Cystic Fibrosis

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Ivacaftor
Sponsored by
Vertex Pharmaceuticals Incorporated
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cystic Fibrosis focused on measuring Cystic Fibrosis

Eligibility Criteria

2 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

Observational Arm

Ivacaftor

Arm Description

Ivacaftor will be administered every 12 hours (q12h) from Day 1 through the Week 84 Visit. The ivacaftor dose will be: 50 mg q12h for subjects 2 to <6 years of age and <14 kg, 75 mg q12h for subjects 2 to <6 years of age and ≥ 14 kg, or 150 mg q12h for subjects ≥ 6 years of age.

Outcomes

Primary Outcome Measures

Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
AE: any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as Non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, Inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first dose of study drug through the end of study participation was considered treatment-emergent.

Secondary Outcome Measures

Absolute Change From Baseline of Parent Study in Sweat Chloride at Week 24, 48, 72 and 84
Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of greater than or equal to (>=) 15 microliter was required for determination of sweat chloride. Baseline was defined as the most recent measurement prior to intake of the first dose of study drug in study 108 Part B (NCT01705145).
Absolute Change From Baseline of Study 109 in Sweat Chloride at Week 24, 48, 72 and 84
Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of >=15 microliter was required for determination of sweat chloride. Baseline is defined as the most recent measurement prior to intake of the first dose of study drug in study 109 (NCT01946412).
Absolute Change From Baseline of Parent Study in Weight at Week 12, 24, 36, 48, 60, 72 and 84
Baseline was defined as the most recent measurement prior to intake of the first dose of study drug in study 108 Part B (NCT01705145)
Absolute Change From Baseline of Study 109 in Weight at Week 12, 24, 36, 48, 60, 72 and 84
Baseline is defined as the most recent measurement prior to intake of the first dose of study drug in study 109 (NCT01946412).
Absolute Change From Baseline of Parent Study in Stature at Week 12, 24, 36, 48, 60, 72 and 84
Stature was measured as height if children could stand unassisted and follow directions; otherwise, stature was measured as length. Baseline was defined as the most recent measurement prior to intake of the first dose of study drug in study 108 Part B (NCT01705145).
Absolute Change From Baseline of Study 109 in Stature at Week 12, 24, 36, 48, 60, 72 and 84
Stature was measured as height if children could stand unassisted and follow directions; otherwise, stature was measured as length. Baseline is defined as the most recent measurement prior to intake of the first dose of study drug in study 109 (NCT01946412).
Absolute Change From Baseline of Parent Study in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84
BMI = (Weight [in kg]) divided by (Stature [in meters]) ^2. Baseline was defined as the most recent measurement prior to intake of the first dose of study drug in study 108 Part B (NCT01705145).
Absolute Change From Baseline of Study 109 in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84
BMI = (Weight [in kg]) divided by (Stature [in meters]) ^2. Baseline is defined as the most recent measurement prior to intake of the first dose of study drug in study 109 (NCT01946412).

Full Information

First Posted
September 16, 2013
Last Updated
December 6, 2016
Sponsor
Vertex Pharmaceuticals Incorporated
Collaborators
Cystic Fibrosis Foundation
search

1. Study Identification

Unique Protocol Identification Number
NCT01946412
Brief Title
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

2. Study Status

Record Verification Date
December 2016
Overall Recruitment Status
Completed
Study Start Date
December 2013 (undefined)
Primary Completion Date
December 2015 (Actual)
Study Completion Date
December 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vertex Pharmaceuticals Incorporated
Collaborators
Cystic Fibrosis Foundation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
Keywords
Cystic Fibrosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
33 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Observational Arm
Arm Type
No Intervention
Arm Title
Ivacaftor
Arm Type
Experimental
Arm Description
Ivacaftor will be administered every 12 hours (q12h) from Day 1 through the Week 84 Visit. The ivacaftor dose will be: 50 mg q12h for subjects 2 to <6 years of age and <14 kg, 75 mg q12h for subjects 2 to <6 years of age and ≥ 14 kg, or 150 mg q12h for subjects ≥ 6 years of age.
Intervention Type
Drug
Intervention Name(s)
Ivacaftor
Other Intervention Name(s)
VX-770, Kalydeco
Primary Outcome Measure Information:
Title
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
AE: any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as Non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, Inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first dose of study drug through the end of study participation was considered treatment-emergent.
Time Frame
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 Outcome Measure Information:
Title
Absolute Change From Baseline of Parent Study in Sweat Chloride at Week 24, 48, 72 and 84
Description
Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of greater than or equal to (>=) 15 microliter was required for determination of sweat chloride. Baseline was defined as the most recent measurement prior to intake of the first dose of study drug in study 108 Part B (NCT01705145).
Time Frame
Baseline (study 108), Week 24, 48, 72 and 84 (study 109)
Title
Absolute Change From Baseline of Study 109 in Sweat Chloride at Week 24, 48, 72 and 84
Description
Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of >=15 microliter was required for determination of sweat chloride. Baseline is defined as the most recent measurement prior to intake of the first dose of study drug in study 109 (NCT01946412).
Time Frame
Baseline (study 109), Week 24, 48, 72 and 84 (study 109)
Title
Absolute Change From Baseline of Parent Study in Weight at Week 12, 24, 36, 48, 60, 72 and 84
Description
Baseline was defined as the most recent measurement prior to intake of the first dose of study drug in study 108 Part B (NCT01705145)
Time Frame
Baseline (study 108), Week 12, 24, 36, 48, 60, 72 and 84 (study 109)
Title
Absolute Change From Baseline of Study 109 in Weight at Week 12, 24, 36, 48, 60, 72 and 84
Description
Baseline is defined as the most recent measurement prior to intake of the first dose of study drug in study 109 (NCT01946412).
Time Frame
Baseline (study 109), Week 12, 24, 36, 48, 60, 72 and 84 (study 109)
Title
Absolute Change From Baseline of Parent Study in Stature at Week 12, 24, 36, 48, 60, 72 and 84
Description
Stature was measured as height if children could stand unassisted and follow directions; otherwise, stature was measured as length. Baseline was defined as the most recent measurement prior to intake of the first dose of study drug in study 108 Part B (NCT01705145).
Time Frame
Baseline (study 108), Week 12, 24, 36, 48, 60, 72 and 84 (study 109)
Title
Absolute Change From Baseline of Study 109 in Stature at Week 12, 24, 36, 48, 60, 72 and 84
Description
Stature was measured as height if children could stand unassisted and follow directions; otherwise, stature was measured as length. Baseline is defined as the most recent measurement prior to intake of the first dose of study drug in study 109 (NCT01946412).
Time Frame
Baseline (study 109), Week 12, 24, 36, 48, 60, 72 and 84 (study 109)
Title
Absolute Change From Baseline of Parent Study in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84
Description
BMI = (Weight [in kg]) divided by (Stature [in meters]) ^2. Baseline was defined as the most recent measurement prior to intake of the first dose of study drug in study 108 Part B (NCT01705145).
Time Frame
Baseline (study 108), Week 12, 24, 36, 48, 60, 72 and 84 (study 109)
Title
Absolute Change From Baseline of Study 109 in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84
Description
BMI = (Weight [in kg]) divided by (Stature [in meters]) ^2. Baseline is defined as the most recent measurement prior to intake of the first dose of study drug in study 109 (NCT01946412).
Time Frame
Baseline (study 109), Week 12, 24, 36, 48, 60, 72 and 84 (study 109)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria (Ivacaftor Arm): Completed the last study visit of the treatment period of the previous study (NCT01705145) 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 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): Subjects who prematurely discontinued from the previous study 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 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 Subjects receiving commercially-available ivacaftor treatment 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adebayo Lawal, M.D.
Organizational Affiliation
Vertex Pharmaceuticals Incorporated
Official's Role
Study Director
Facility Information:
City
Birmingham
State/Province
Alabama
Country
United States
City
Denver
State/Province
Colorado
Country
United States
City
Atlanta
State/Province
Georgia
Country
United States
City
Indianapolis
State/Province
Indiana
Country
United States
City
Boston
State/Province
Massachusetts
Country
United States
City
Grand Rapids
State/Province
Michigan
Country
United States
City
Minneapolis
State/Province
Minnesota
Country
United States
City
Kansas city
State/Province
Missouri
Country
United States
City
Omaha
State/Province
Nebraska
Country
United States
City
Salt Lake City
State/Province
Utah
Country
United States
City
Richmond
State/Province
Virginia
Country
United States
City
Seattle
State/Province
Washington
Country
United States
City
Vancouver
State/Province
British Columbia
Country
Canada
City
Edinburgh
Country
United Kingdom
City
Liverpool
Country
United Kingdom
City
London
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
31053538
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.
Results Reference
derived

Learn more about this trial

Roll-Over Study of Ivacaftor in Cystic Fibrosis Pediatric Subjects With a CF Transmembrane Conductance Regulator Gene (CFTR) Gating Mutation

We'll reach out to this number within 24 hrs