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

Rollover Study of Ivacaftor in Subjects With Cystic Fibrosis and a Non G551D CFTR Mutation

Sponsors

Lead sponsor: Vertex Pharmaceuticals Incorporated

Collaborator: Cystic Fibrosis Foundation

Source Vertex Pharmaceuticals Incorporated
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.

Overall Status Completed
Start Date February 2013
Completion Date April 2016
Primary Completion Date April 2016
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) in Ivacaftor Arm Day 1 up to Week 108 (Study 112)
Secondary Outcome
Measure Time Frame
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 Baseline, Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104 (Study 112)
Absolute Change From Baseline in Body Mass Index (BMI) at Week 2,12, 24, 36, 48, 60, 72, 84, 96 and 104 Baseline, Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104 (Study 112)
Absolute Change From Baseline in Sweat Chloride at Week 2, 24, 48 and 104 Baseline, Week 2, 24, 48 and 104 (Study 112)
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 Baseline, Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104 (Study 112)
Number of Pulmonary Exacerbations Events Through Week 104 (Study 112)
Number of Participants With Serious Adverse Events (SAEs) in Observational Arm up to 2 years (Study 112)
Enrollment 125
Condition
Intervention

Intervention type: Drug

Intervention name: Ivacaftor

Description: 150 mg tablet, oral use, every 12 hours (q12h)

Arm group label: Ivacaftor

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.

Gender: All

Minimum age: 6 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Joseph Pilewski, MD Principal Investigator University of Pittsburgh
Location
facility
| Birmingham, Alabama, United States
| Palo Alto, California, United States
| Denver, Colorado, United States
| Hartford, Connecticut, United States
| Tampa, Florida, United States
| Atlanta, Georgia, United States
| Chicago, Illinois, United States
| Iowa City, Iowa, United States
| Lexington, Kentucky, United States
| Baltimore, Maryland, United States
| Boston, Massachusetts, United States
| Ann Arbor, Michigan, United States
| Detroit, Michigan, United States
| Grand Rapids, Michigan, United States
| Minneapolis, Minnesota, United States
| St. Louis, Missouri, United States
| Omaha, Nebraska, United States
| New York, New York, United States
| Syracuse, New York, United States
| Valhalla, New York, United States
| Chapel Hill, North Carolina, United States
| Philadelphia, Pennsylvania, United States
| Pittsburgh, Pennsylvania, United States
| Charleston, South Carolina, United States
| Nashville, Tennessee, United States
| Dallas, Texas, United States
| Fort Worth, Texas, United States
| Houston, Texas, United States
| Salt Lake City, Utah, United States
| Richmond, Virginia, United States
| Seattle, Washington, United States
| Morgantown, West Virginia, United States
| Madison, Wisconsin, United States
| Leuven, Belgium
| Montpellier, France
| Paris, France
| Belfast, United Kingdom
| Edinburgh, United Kingdom
Location Countries

Belgium

France

United Kingdom

United States

Verification Date

April 2017

Responsible Party

Responsible party type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: Ivacaftor

Arm group type: Experimental

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 group label: Observational

Arm group type: No Intervention

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.

Acronym KONTINUE
Study Design Info

Allocation: Non-Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov