A Study of Lumacaftor in Combination With Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older Who Are Homozygous for the F508del-CFTR Mutation (TRAFFIC)

Vertex Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Cystic Fibrosis, Homozygous for the F508del CFTR Mutation

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT01807923

VX12-809-103

Details and patient eligibility

About

The primary objective of the study was to evaluate the efficacy of lumacaftor in combination with ivacaftor at Week 24 in participants aged 12 years and older with cystic fibrosis (CF) who are homozygous for the F508del mutation on the CF transmembrane conductance regulator (CFTR) gene.

Full description

This was a Phase 3, randomized, double-blind, placebo-controlled, parallel-group multicenter study of orally administered lumacaftor in combination with ivacaftor in participants aged 12 years and older with CF who are homozygous for the F508del-CFTR mutation.

The study included a Screening Period (Day -28 through Day -1), a Treatment Period (Day 1 [first dose of study drug] to Week 24 ± 5 days), and a Safety Follow-up Visit (4 weeks ± 7 days after the Week 24 Visit).

Enrollment: 559 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Confirmed diagnosis of CF
• Homozygous for the F508del CFTR mutation
• Forced expiratory volume in 1 second (FEV1) greater than or equal to (>=) 40 percent (%) and less than or equal to (=<) 90% of predicted normal for age, sex, and height
• Willing to remain on a stable CF medication regimen through Week 24 or, if applicable, the Safety Follow up Visit

Exclusion criteria

• An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before first dose of study drug
• History of solid organ or hematological transplantation
• History of alcohol or drug abuse in the past year
• Ongoing or prior participation in an investigational drug study (including studies investigating lumacaftor and/or ivacaftor) within 30 days of screening
• Use of strong inhibitors, moderate inducers or strong inducers of Cytochrome P450 3A (CYP3A) within 14 days before Day 1 of dosing

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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559 participants in 3 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Placebo matched to lumacaftor (LUM, VX-809) and ivacaftor (IVA, VX-770) tablet every 12 hours (q12h), up to Week 24.

Treatment:

Drug: Placebo

LUM 600 mg qd/IVA 250 mg q12h

Experimental group

Description:

LUM 600 milligram (mg) plus IVA 250 mg fixed-dose combination (FDC) tablet in the morning and IVA 250 mg film-coated tablet in the evening, up to Week 24.

Treatment:

Drug: Ivacaftor

Drug: Lumacaftor Plus Ivacaftor Combination

LUM 400 mg q12h/ IVA 250 mg q12h

Experimental group

Description:

LUM 400 mg plus IVA 250 mg FDC tablet in the morning and in the evening, up to Week 24.

Treatment:

Drug: Lumacaftor Plus Ivacaftor Combination