Back to resultsRollover Study of Ivacaftor in Subjects With Cystic Fibrosis and a Non G551D CFTR Mutation (KONTINUE)
Primary Purpose
Cystic Fibrosis
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Ivacaftor
Sponsored by
About this trial
This is an interventional treatment trial for Cystic Fibrosis
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Ivacaftor
Observational
Arm Description
Participants who received Ivacaftor 150 milligram (mg) tablet and/or Placebo matched to Ivacaftor tablet orally, every 12 hours (q12h) in the previous study VX11-770-110 (Study 110; NCT01614457), VX12-770-111 (Study 111; NCT01614470) or VX12-770-113 (Study 113; NCT01685801); received Ivacaftor 150 mg tablet q12h in this VX12-770-112 (Study 112; NCT01707290) up to 104 weeks.
Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet, orally, q12h in the previous Study 110 (NCT01614457) or Study 111 (NCT01614470), were observed (did not receive study drug) in this Study 112 (NCT01707290) for up to 2 years.
Outcomes
Primary Outcome Measures
Number of Participants With Treatment Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) in Ivacaftor Arm
AE: any untoward medical occurrence in a participants 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 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, In-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. TEAEs were defined as adverse events with start date or increased severity on and after the first dose of study drug through Week 108.
Secondary Outcome Measures
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
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 6 to 17 years and for female participants aged 6 to 15 years. Baseline was defined as the most recent measurement before intake of the first dose of study drug (Ivacaftor) in Study 112. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.
Absolute Change From Baseline in Body Mass Index (BMI) at Week 2,12, 24, 36, 48, 60, 72, 84, 96 and 104
BMI was defined as weight in kg divided by height in m^2. Baseline was defined as the most recent measurement before intake of the first dose of study drug (Ivacaftor) in Study 112. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.
Absolute Change From Baseline in Sweat Chloride at Week 2, 24, 48 and 104
Sweat samples were collected using an approved collection device. Baseline was defined as the most recent measurement before intake of the first dose of study drug (Ivacaftor) in Study 112. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.
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
The CFQ-R is a validated participant reported outcome measuring health related quality of life for participants with CF. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health related quality of life. Baseline was defined as the most recent measurement before intake of the first dose of study drug (ivacaftor) in Study 112. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.
Number of Pulmonary Exacerbations Events
Pulmonary exacerbation events include those events which require treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms. The number of events were reported. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.
Number of Participants With Serious Adverse Events (SAEs) in Observational Arm
SAE was defined as a 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, In-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event.
Full Information
NCT ID
NCT01707290
First Posted
October 9, 2012
Last Updated
April 3, 2017
Sponsor
Vertex Pharmaceuticals Incorporated
Collaborators
Cystic Fibrosis Foundation
1. Study Identification
Unique Protocol Identification Number
NCT01707290
Brief Title
Rollover Study of Ivacaftor in Subjects With Cystic Fibrosis and a Non G551D CFTR Mutation
Acronym
KONTINUE
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
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
February 2013 (undefined)
Primary Completion Date
April 2016 (Actual)
Study Completion Date
April 2016 (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
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
125 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ivacaftor
Arm Type
Experimental
Arm Description
Participants who received Ivacaftor 150 milligram (mg) tablet and/or Placebo matched to Ivacaftor tablet orally, every 12 hours (q12h) in the previous study VX11-770-110 (Study 110; NCT01614457), VX12-770-111 (Study 111; NCT01614470) or VX12-770-113 (Study 113; NCT01685801); received Ivacaftor 150 mg tablet q12h in this VX12-770-112 (Study 112; NCT01707290) up to 104 weeks.
Arm Title
Observational
Arm Type
No Intervention
Arm Description
Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet, orally, q12h in the previous Study 110 (NCT01614457) or Study 111 (NCT01614470), were observed (did not receive study drug) in this Study 112 (NCT01707290) for up to 2 years.
Intervention Type
Drug
Intervention Name(s)
Ivacaftor
Other Intervention Name(s)
Kalydeco, VX-770
Intervention Description
150 mg tablet, oral use, every 12 hours (q12h)
Primary Outcome Measure Information:
Title
Number of Participants With Treatment Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) in Ivacaftor Arm
Description
AE: any untoward medical occurrence in a participants 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 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, In-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. TEAEs were defined as adverse events with start date or increased severity on and after the first dose of study drug through Week 108.
Time Frame
Day 1 up to Week 108 (Study 112)
Secondary Outcome Measure Information:
Title
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
Description
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 6 to 17 years and for female participants aged 6 to 15 years. Baseline was defined as the most recent measurement before intake of the first dose of study drug (Ivacaftor) in Study 112. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.
Time Frame
Baseline, Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104 (Study 112)
Title
Absolute Change From Baseline in Body Mass Index (BMI) at Week 2,12, 24, 36, 48, 60, 72, 84, 96 and 104
Description
BMI was defined as weight in kg divided by height in m^2. Baseline was defined as the most recent measurement before intake of the first dose of study drug (Ivacaftor) in Study 112. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.
Time Frame
Baseline, Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104 (Study 112)
Title
Absolute Change From Baseline in Sweat Chloride at Week 2, 24, 48 and 104
Description
Sweat samples were collected using an approved collection device. Baseline was defined as the most recent measurement before intake of the first dose of study drug (Ivacaftor) in Study 112. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.
Time Frame
Baseline, Week 2, 24, 48 and 104 (Study 112)
Title
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
Description
The CFQ-R is a validated participant reported outcome measuring health related quality of life for participants with CF. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health related quality of life. Baseline was defined as the most recent measurement before intake of the first dose of study drug (ivacaftor) in Study 112. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.
Time Frame
Baseline, Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104 (Study 112)
Title
Number of Pulmonary Exacerbations Events
Description
Pulmonary exacerbation events include those events which require treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms. The number of events were reported. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.
Time Frame
Through Week 104 (Study 112)
Title
Number of Participants With Serious Adverse Events (SAEs) in Observational Arm
Description
SAE was defined as a 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, In-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event.
Time Frame
up to 2 years (Study 112)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joseph Pilewski, MD
Organizational Affiliation
University of Pittsburgh
Official's Role
Principal Investigator
Facility Information:
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Birmingham
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Palo Alto
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Leuven
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Belfast
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Edinburgh
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United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
32965659
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.
Results Reference
derived
PubMed Identifier
26070913
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.
Results Reference
derived
Learn more about this trial
Rollover Study of Ivacaftor in Subjects With Cystic Fibrosis and a Non G551D CFTR Mutation
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