A Phase 3 Rollover Study of Lumacaftor in Combination With Ivacaftor in Subjects 12 Years and Older With Cystic Fibrosis

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT01931839
• Date of registration: 26/08/2013
• Prospective Registration: Yes
• Primary sponsor: Vertex Pharmaceuticals Incorporated
• Public title: A Phase 3 Rollover Study of Lumacaftor in Combination With Ivacaftor in Subjects 12 Years and Older With Cystic Fibrosis
• Scientific title: A Phase 3, Rollover Study to Evaluate the Safety and Efficacy of Long-term Treatment With Lumacaftor in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Homozygous or Heterozygous for the F508del-CFTR Mutation
• Date of first enrolment: October 2013
• Target sample size: 1164
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01931839
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 3

Countries of recruitment

Australia, Austria, Belgium, Canada, Czech Republic, Denmark, France, Germany, Ireland, Italy, Netherlands, Spain, Sweden, United Kingdom, United States

Key inclusion & exclusion criteria

Inclusion Criteria:

- Signed informed consent form (ICF), and where appropriate, signed assent form.

- Participants entering the Part A Treatment Cohort: Completed 24 weeks of study drug
treatment in Study 103 or Study 104 and elect to enroll in Part A treatment cohort.

- Participants entering the Part B Treatment Cohort: Completed 56 days of study drug
treatment in Cohort 4 of Study 102 and elect to enroll in Part B treatment cohort.

- Participants entering the Part A Observational Cohort: Completed 24 weeks of study
drug treatment in Study 103 or Study 104, but do not elect to enroll in the Part A
Treatment Cohort or do not qualify to enroll in Part A treatment cohort.

- Willing to remain on a stable CF medication regimen through the end of study (Part A
and Part B Treatment Cohorts only).

Exclusion Criteria:

- Any comorbidity or laboratory abnormality 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 participant (e.g., cirrhosis with portal hypertension).

- Pregnant and nursing females. Females of childbearing potential must have a negative
pregnancy test at the Day 1 Visit.

- History of drug intolerance in the prior study that would pose an additional risk to
the participant in the opinion of investigator or Vertex.

- History of poor compliance with study drug and/or procedures in the previous study as
deemed by the investigator.

- Participation in an investigational drug trial (including studies investigating
lumacaftor and/or ivacaftor, or studies requiring blood collections with or without
administration of study drug)



Age minimum: 12 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Cystic Fibrosis, Homozygous or Heterozygous for the F508del-CFTR Mutation

Intervention(s)

Drug: Lumacaftor Plus Ivacaftor Combination

Drug: Ivacaftor

Primary Outcome(s)

Part A Treatment Cohort: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time Frame: Day 1 up to Week 105 (Study 105)]

Part B Treatment Cohort: Number of Participants With Treatment-Emergent AEs and SAEs [Time Frame: Day 1 up to Week 105 (Study 105)]

Secondary Outcome(s)

Part A Treatment Cohort: Absolute Change From Baseline in Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Domain Score at Day 15, Week 8, 16, 24, 48 and 72 [Time Frame: Baseline (Study 103/104/105), Day 15, Week 8, 16, 24, 48, 72 (Study 105)]

Part B Treatment Cohort: Absolute Change From Baseline in Percent Predicted FEV1 at Day 15, Week 8, 16, 24, 36, 48, 60 and 72 [Time Frame: Baseline (Study 102), Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105)]

Part A Treatment Cohort: Relative Change From Baseline in Percent Predicted FEV1 at Day 15, Week 8, 16, 24, 36, 48, 60 and 72 [Time Frame: Baseline (Study 103/104/105), Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105)]

Part A Treatment Cohort: Time-to-First Pulmonary Exacerbation [Time Frame: Baseline (Study 103/104) up to Week 100 (Study 105) for Arm 1 and 3 (Cumulative study period); Baseline (Study 105) up to Week 100 (Study 105) for Arm 2 and 4 (current study period)]

Part B Treatment Cohort: Percentage of Participants With Response Based on Relative Change in Percent Predicted FEV1 From Baseline [Time Frame: Baseline (Study 102), Day 15, Week 8, 16, 24, 36, 48, 60, 72 (Study 105)]

Part A Treatment Cohort: Absolute Change From Baseline in BMI Z-score at Day 15, Week 8, 16, 24, 36, 48, 60 and 72 [Time Frame: Baseline (Study 103/104/105), Day 15, Week 8, 16, 24, 36, 48, 60, 72 (Study 105)]

Part A Treatment Cohort: Absolute Change From Baseline in Body Weight at Day 15, Week 8, 16, 24, 36, 48, 60 and 72 [Time Frame: Baseline (Study 103/104/105), Day 15, Week 8, 16, 24, 36, 48, 60, 72 (Study 105)]

Part A Treatment Cohort: Percentage of Participants With at Least 1 Pulmonary Exacerbation [Time Frame: Baseline (Study 103/104) up to Week 100 (Study 105) for Arm 1 and 3 (Cumulative study period); Baseline (Study 105) up to Week 100 (Study 105) for Arm 2 and 4 (current study period)]

Part B Treatment Cohort: Absolute Change From Baseline in Body Weight at Day 15, Week 8, 16, 24, 36, 48, 60 and 72 [Time Frame: Baseline (Study 102), Day 15, Week 8, 16, 24, 36, 48, 60, 72 (Study 105)]

Part B Treatment Cohort: Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 15, Week 8, 16, 24, 48 and 72 [Time Frame: Baseline (Study 102 Study), Day 15, Week 8, 16, 24, 48, 72 (Study 105)]

Part A Observation Cohort: Number of Participants With Serious Adverse Events (SAEs) [Time Frame: up to 2 years]

Part A Treatment Cohort: Number of Pulmonary Exacerbations Events Per Patient-Year [Time Frame: Baseline (Study 103/104) up to Week 100 (Study 105) for Arm 1 and 3 (Cumulative study period); Baseline (Study 105) up to Week 100 (Study 105) for Arm 2 and 4 (current study period)]

Part A Treatment Cohort: Percentage of Participants With Response Based on Relative Change in Percent Predicted FEV1 From Baseline [Time Frame: Baseline (Study 103/104/105); Day 15, Week 8, 16, 24, 36, 48, 60, 72, 84, 96 (Study 105)]

Part B Treatment Cohort: Relative Change From Baseline in Percent Predicted FEV1 at Day 15, Week 8, 16, 24, 36, 48, 60 and 72 [Time Frame: Baseline (Study 102), Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105)]

Part A Treatment Cohort: Absolute Change From Baseline in Body Mass Index (BMI) at Day 15, Week 8, 16, 24, 36, 48, 60 and 72 [Time Frame: Baseline (Study 103/104/105), Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105)]

Part A Treatment Cohort: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) At Day 15, Week 8, 16, 24, 36, 48, 60 and 72 [Time Frame: Baseline (Study 103/104/105); Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105)]

Part B Treatment Cohort: Absolute Change From Baseline in BMI at Day 15, Week 8, 16, 24, 36, 48, 60 and 72 [Time Frame: Baseline (Study 102), Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105)]

Secondary ID(s)

VX12-809-105

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 12/05/2017
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01931839