A Study Evaluating the Safety and Efficacy of VX-659 Combination Therapy in Subjects With Cystic Fibrosis

Vertex Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Cystic Fibrosis

Treatments: Drug: TEZ/IVA; Drug: Placebo (matched to VX-659/TEZ/IVA); Drug: VX-659; Drug: TEZ; Drug: VX-561; Drug: IVA; Drug: Placebo (matched to VX-659/TEZ/VX-561)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03224351

2016-003585-11 (EudraCT Number)

VX16-659-101

Details and patient eligibility

About

This is a Phase 2, randomized, double-blind, placebo- and tezacaftor/ivacaftor (TEZ/IVA)-controlled, parallel-group, 3-part, multicenter study designed to evaluate the safety and efficacy of VX-659 in triple combination (TC) with TEZ and IVA in subjects with cystic fibrosis (CF) who are homozygous for the F508del mutation of the CF transmembrane conductance regulator (CFTR) gene (F/F genotype), or who are heterozygous for the F508del mutation and a minimal function (MF) CFTR mutation not likely to respond to TEZ, IVA, or TEZ/IVA (F/MF genotypes).

Enrollment: 124 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Body weight ≥35 kg.

• Subjects must have an eligibleCFTR genotype.

  • Part 1 and Part 3: Heterozygous for F508del and an MF mutation (F/MF)
  • Part 2: Homozygous for F508del (F/F)

• FEV1 value ≥40% and ≤90% of predicted mean for age, sex, and height

Key Exclusion Criteria:

• History of clinically significant cirrhosis with or without portal hypertension.
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency
• Lung infection with organisms associated with a more rapid decline in pulmonary status.
• History of solid organ or hematological transplantation.

Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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124 participants in 8 patient groups, including a placebo group

Part 1: Placebo

Placebo Comparator group

Description:

Participants received placebo matched to VX-659/TEZ/IVA in TC treatment period for 4 weeks and placebo matched TEZ/IVA in washout period for 4 days.

Treatment:

Drug: Placebo (matched to VX-659/TEZ/IVA)

Part 1: VX-659/TEZ/IVA TC - Low Dose

Experimental group

Description:

Participants received VX-659 80 milligram (mg) once daily (qd)/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days.

Treatment:

Drug: IVA

Drug: VX-659

Drug: TEZ/IVA

Part 1: VX-659/TEZ/IVA TC - Medium Dose

Experimental group

Description:

Participants received VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days.

Treatment:

Drug: IVA

Drug: VX-659

Drug: TEZ/IVA

Part 1: VX-659/TEZ/IVA TC - High Dose

Experimental group

Description:

Participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days.

Treatment:

Drug: IVA

Drug: VX-659

Drug: TEZ/IVA

Part 2: TEZ/IVA

Active Comparator group

Description:

Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks.

Treatment:

Drug: IVA

Drug: TEZ/IVA

Part 2: VX-659/TEZ/IVA TC

Experimental group

Description:

Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks.

Treatment:

Drug: IVA

Drug: VX-659

Drug: TEZ/IVA

Part 3: Placebo

Placebo Comparator group

Description:

Participants received placebo matched to VX-659/TEZ/VX-561 in TC treatment period for 4 weeks.

Treatment:

Drug: Placebo (matched to VX-659/TEZ/VX-561)

Part 3: VX-659/TEZ/VX-561 TC

Experimental group

Description:

Participants received VX-659 400 mg qd/TEZ 100 mg qd/VX-561 200 mg qd in TC treatment period for 4 weeks.

Treatment:

Drug: VX-659

Drug: VX-561

Drug: TEZ