A Study to Evaluate the Safety and Efficacy of VX-121 Combination Therapy in Subjects With Cystic Fibrosis

Vertex Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Cystic Fibrosis

Treatments: Drug: Placebo; Drug: VX-121; Drug: TEZ; Drug: VX-561; Drug: TEZ/IVA; Drug: IVA

Study type: Interventional

Funder types: Industry

Identifiers

NCT03912233

VX18-121-101

Details and patient eligibility

About

The purpose of this study is to evaluate the safety, tolerability and efficacy of VX-121 combination therapy in subjects with cystic fibrosis (CF).

Enrollment: 87 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Part 1: Heterozygous for F508del and an MF mutation (F/MF)
• Part 2: Homozygous for F508del (F/F)
• FEV1 value ≥40% and ≤90% of the predicted mean for age, sex, and height

Key Exclusion Criteria:

• History of clinically significant cirrhosis with or without portal hypertension
• 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: Sequential Assignment

Masking: Quadruple Blind

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87 participants in 6 patient groups, including a placebo group

Part 1: Placebo

Placebo Comparator group

Description:

Participants received placebo matched to VX-121/TEZ/VX-561 triple combination (TC) for 4 weeks in the treatment period and placebo matched to TEZ/VX-561 for 18 days in the washout period.

Treatment:

Drug: Placebo

Part 1: VX-121/TEZ/VX-561 TC - Low Dose

Experimental group

Description:

Participants received VX-121 5 milligram (mg) once daily (qd)/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period

Treatment:

Drug: VX-121

Drug: VX-561

Drug: TEZ

Part 1: VX-121/TEZ/VX-561 TC - Medium Dose

Experimental group

Description:

Participants received VX-121 10 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period.

Treatment:

Drug: VX-121

Drug: VX-561

Drug: TEZ

Part 1: VX-121/TEZ/VX-561 TC - High Dose

Experimental group

Description:

Participants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period.

Treatment:

Drug: VX-121

Drug: VX-561

Drug: TEZ

Part 2: TEZ/IVA

Active Comparator group

Description:

Following run-in period with TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) for 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the treatment period and TEZ 100 mg/IVA 150 mg q12h for 4 weeks in the washout period.

Treatment:

Drug: TEZ/IVA

Drug: IVA

Part 2: VX-121/TEZ/VX-561 TC - High Dose

Experimental group

Description:

Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the washout period.

Treatment:

Drug: VX-121

Drug: VX-561

Drug: TEZ