Study of VX-121 in Healthy Subjects and in Subjects With Cystic Fibrosis

Vertex Pharmaceuticals

Status and phase: Completed; Phase 2; Phase 1

Conditions: Cystic Fibrosis

Treatments: Drug: Placebo (matched to IVA); Drug: Placebo (matched to VX-121 tablet); Drug: VX-121 (Tablet); Drug: Placebo (matched to TEZ/IVA); Drug: Placebo (matched to VX-121 suspension); Drug: VX-121 (Suspension); Drug: IVA; Drug: TEZ/IVA

Study type: Interventional

Funder types: Industry

Identifiers

NCT03768089

2018-000126-55 (EudraCT Number)

VX17-121-001

Details and patient eligibility

About

The purpose of this study is to evaluate safety and tolerability of VX-121 in healthy subjects and in subjects with cystic fibrosis (CF).

Enrollment: 115 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Part A, B, and C: Healthy Volunteers

  • Female subjects must be of non-childbearing potential
  • Between the ages of 18 and 55 years, inclusive
  • Body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive, and a total body weight >50 kg

• Part D: Subjects with CF

  • Heterozygous for F508del and an MF mutation (F/MF)
  • FEV1 value ≥40% and ≤90% of predicted mean for age, sex, and height
  • Body weight ≥35 kg

Key Exclusion Criteria:

• Part A, B and C: Healthy Volunteers

  • Any condition possibly affecting drug absorption
  • History of febrile illness or other acute illness within 5 days before the first study drug dose

• Part D: Subjects with CF

  • History of clinically significant cirrhosis with or without portal hypertension
  • History of solid organ or hematological transplantation
  • Lung infection with organisms associated with a more rapid decline in pulmonary status

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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115 participants in 18 patient groups, including a placebo group

Part A: Pooled Placebo (Cohorts A1-5; Except A3)

Placebo Comparator group

Description:

Participants received single dose of placebo matched to VX-121.

Treatment:

Drug: Placebo (matched to VX-121 suspension)

Part A: VX-121 (Cohort A1)

Experimental group

Description:

Participants received single dose of VX-121 10 milligrams (mg).

Treatment:

Drug: VX-121 (Suspension)

Part A: VX-121 (Cohort A2)

Experimental group

Description:

Participants received single dose of VX-121 20 mg.

Treatment:

Drug: VX-121 (Suspension)

Part A: VX-121 (Cohort A3)

Experimental group

Description:

Participants received single dose of VX-121 5 mg or matched placebo without milk, followed by open label VX-121 5 mg with milk.

Treatment:

Drug: Placebo (matched to VX-121 suspension)

Drug: VX-121 (Suspension)

Part A: VX-121 (Cohort A4)

Experimental group

Description:

Participants received single dose of VX-121 40 mg.

Treatment:

Drug: VX-121 (Suspension)

Part A: VX-121 (Cohort A5)

Experimental group

Description:

Participants received single dose of VX-121 60 mg.

Treatment:

Drug: VX-121 (Suspension)

Part A: VX-121 (Cohort A9)

Experimental group

Description:

Participants received single dose of VX-121 10 mg suspension on Day 1, VX-121 10 mg tablet on Day 9, followed by VX-121 10 mg tablet with milk on Day 17.

Treatment:

Drug: VX-121 (Tablet)

Drug: VX-121 (Suspension)

Part B: Pooled Placebo (Cohorts B1-4)

Placebo Comparator group

Description:

Participants received placebo matched to VX-121 for 10 days.

Treatment:

Drug: Placebo (matched to VX-121 suspension)

Part B: VX-121 (Cohort B1)

Experimental group

Description:

Participants received VX-121 10 mg once daily (qd) for 10 days.

Treatment:

Drug: VX-121 (Suspension)

Part B: VX-121 (Cohort B2)

Experimental group

Description:

Participants received VX-121 20 mg qd for 10 days.

Treatment:

Drug: VX-121 (Suspension)

Part B: VX-121 (Cohort B3)

Experimental group

Description:

Participants received VX-121 40 mg qd for 10 days.

Treatment:

Drug: VX-121 (Suspension)

Part B: VX-121 (Cohort B4)

Experimental group

Description:

Participants received VX-121 60 mg qd for 10 days.

Treatment:

Drug: VX-121 (Suspension)

Part C: Pooled Placebo (Cohorts C1-3)

Placebo Comparator group

Description:

Participants received placebo matched to VX-121/TEZ/IVA for 14 days.

Treatment:

Drug: Placebo (matched to IVA)

Drug: Placebo (matched to TEZ/IVA)

Drug: Placebo (matched to VX-121 suspension)

Part C: VX-121 (Cohort C1)

Experimental group

Description:

Participants received VX-121 10 mg qd/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) for 14 days.

Treatment:

Drug: TEZ/IVA

Drug: IVA

Drug: VX-121 (Suspension)

Part C: VX-121 (Cohort C2)

Experimental group

Description:

Participants received VX-121 20 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 14 days.

Treatment:

Drug: TEZ/IVA

Drug: IVA

Drug: VX-121 (Suspension)

Part C: VX-121 (Cohort C3)

Experimental group

Description:

Participants received VX-121 5 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 14 days.

Treatment:

Drug: TEZ/IVA

Drug: IVA

Drug: VX-121 (Suspension)

Part D: Placebo

Placebo Comparator group

Description:

Participants received placebo matched to VX-121/TEZ/IVA for 4 weeks.

Treatment:

Drug: Placebo (matched to IVA)

Drug: Placebo (matched to TEZ/IVA)

Drug: Placebo (matched to VX-121 tablet)

Part D: VX-121/TEZ/IVA

Experimental group

Description:

Participants received VX-121 5 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks.

Treatment:

Drug: TEZ/IVA

Drug: IVA

Drug: VX-121 (Tablet)