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

Vertex Pharmaceuticals

Status and phase: Completed; Phase 3

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

Treatments: Drug: Ivacaftor; Drug: Lumacaftor Plus Ivacaftor Combination

Study type: Interventional

Funder types: Industry

Identifiers

NCT01931839

VX12-809-105

Details and patient eligibility

About

The purpose of this study is to evaluate the efficacy and safety of long-term treatment with lumacaftor in combination with ivacaftor in people 12 years and older with Cystic Fibrosis.

Full description

This is a Phase 3, parallel group, multicenter, rollover study in participants with CF who are homozygous or heterozygous for the F508del CFTR mutation and who previously participated in Study 103 (Study VX12-809-103, NCT01807923), Study 104 (Study VX12-809-104, NCT01807949), or Cohort 4 of Study 102 (Study VX09-809-102, NCT01225211).

Enrollment: 1,164 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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1,164 participants in 7 patient groups

Arm 1 Part A: LUM 600 mg qd/ IVA 250 mg q12h

Experimental group

Description:

Participants who received lumacaftor (LUM, VX-809) 600 milligram (mg) plus ivacaftor (IVA, VX-770) 250 mg fixed-dose combination (FDC) tablet orally in the morning and IVA 250 mg film-coated tablet orally in the evening, in the previous study VX12-809-103 or VX12-809-104, and will receive the same treatment in this study VX12-809-105 up to Week 96.

Treatment:

Drug: Lumacaftor Plus Ivacaftor Combination

Drug: Ivacaftor

Arm 2 Part A: Placebo - LUM 600 mg qd/ IVA 250 mg q12h

Experimental group

Description:

Participants who received placebo matched to LUM and IVA tablet in the previous study VX12-809-103 or VX12-809-104, and will receive LUM 600 mg plus IVA 250 mg FDC tablet orally in the morning and IVA 250 mg film-coated tablet orally in the evening in this study VX12-809-105 up to Week 96.

Treatment:

Drug: Lumacaftor Plus Ivacaftor Combination

Drug: Ivacaftor

Arm 3 Part A: LUM 400 mg q12h/ IVA 250 mg q12h

Experimental group

Description:

Participants who received LUM 400 mg plus IVA 250 mg FDC tablet orally in the morning and evening in the previous study VX12-809-103 or VX12-809-104, and will receive the same treatment in this study VX12-809-105 up to Week 96.

Treatment:

Drug: Lumacaftor Plus Ivacaftor Combination

Arm 4 Part A: Placebo - LUM 400 mg q12h/ IVA 250 mg q12h

Experimental group

Description:

Participants who received placebo matched to LUM and IVA tablet in the previous study VX12-809-103 or VX12-809-104, and will receive LUM 400 mg plus IVA 250 mg FDC tablet orally in the morning and evening in this study VX12-809-105 up to Week 96.

Treatment:

Drug: Lumacaftor Plus Ivacaftor Combination

Arm 5 Part A: Observational Cohort

No Intervention group

Description:

Participants who received either LUM 600 mg plus IVA 250 mg FDC tablet orally in the morning and IVA 250 mg film-coated tablet orally in the evening OR LUM 400 mg plus IVA 250 mg FDC tablet orally in the morning and evening OR placebo matched to LUM and IVA in the morning and evening, in the previous study VX12-809-103 or VX12-809-104, and will be observed (will not receive study drug) in this study VX12-809-105 for up to 2 years.

Arm 6 Part B: LUM 400 mg q12h/ IVA 250 mg q12h

Experimental group

Description:

Participants who received LUM 400 mg plus IVA 250 mg FDC tablet orally in the morning and evening in Cohort 4 of the previous study VX09-809-102, and will receive the same treatment in this study VX12-809-105 up to Week 96.

Treatment:

Drug: Lumacaftor Plus Ivacaftor Combination

Arm 7 Part B: Placebo - LUM 400 mg q12h/ IVA 250 mg q12h

Experimental group

Description:

Participants who received placebo matched to LUM and IVA tablet in Cohort 4 of the previous study VX09-809-102, and will receive LUM 400 mg plus IVA 250 mg FDC tablet orally in the morning and evening in this study VX12-809-105 up to Week 96.

Treatment:

Drug: Lumacaftor Plus Ivacaftor Combination