Evaluation of VX-828 in Healthy Participants and in Participants With Cystic Fibrosis

Vertex Pharmaceuticals

Status and phase: Enrolling; Phase 1

Conditions: Cystic Fibrosis

Treatments: Drug: VX-118; Drug: VX-828; Drug: Placebo; Drug: Midazolam; Drug: Deutivacaftor; Drug: Itraconazole; Drug: Tezacaftor

Study type: Interventional

Funder types: Industry

Identifiers

NCT06154447

VX23-828-001

Details and patient eligibility

About

The purpose of the study is to evaluate safety, tolerability, and pharmacokinetics of VX-828 and VX-828 in triple combination (TC) with Tezacaftor (TEZ)/ VX-118 or TEZ/ deutivacaftor (D-IVA) in healthy participants and VX-828 in combination with D-IVA with or without TEZ in participants with cystic fibrosis (CF).

Full description

This clinical trial information was submitted voluntarily under the applicable law and, therefore, certain submission deadlines may not apply. (That is, clinical trial information for this applicable clinical trial was submitted under section 402(j)(4)(A) of the Public Health Service Act and 42 CFR 11.60 and is not subject to the deadlines established by sections 402(j)(2) and (3) of the Public Health Service Act or 42 CFR 11.24 and 11.44.).

Enrollment: 255 estimated patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

Parts A-D:

• Participants between the ages of 18 and 55 years
• Body mass index (BMI) of 18.0 to 32.0 kilogram per meter square (kg/m^2)
• A total body weight of more than (>) 50 kg
• Nonsmoker or ex-smoker for at least 3 months before screening with current nonsmoking status confirmed by urine or blood cotinine at screening
• Cohort C2 only: Willing to provide a single DNA sample

Part E:

• Participants 18 years or older
• Confirmed diagnosis of CF as determined by the investigator
• A total body weight of more than or equal to (>=) 35 kg
• Participants must be heterozygous for F508del with a second CFTR allele carrying a minimal function mutation that is not responsive to ELX/TEZ/IVA therapy
• Participants must have a forced expiratory volume in 1 second (FEV1) of greater than or equal to (≥) 40% of predicted normal for age, sex, and height

Key Exclusion Criteria:

Parts A-D:

• History of febrile illness or other acute illness within 14 days before the first dose of study drug
• Any condition possibly affecting drug absorption

Part E:

• An acute illness not related to CF (e.g., gastroenteritis) within 14 days before the first dose of study drug
• History of solid organ or hematological transplantation
• History of clinically significant cirrhosis with or without portal hypertension
• Lung infection with organisms associated with a more rapid decline in pulmonary status

Other protocol defined Inclusion/Exclusion criteria will apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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255 participants in 8 patient groups, including a placebo group

Part A: Single Ascending Dose (SAD)

Experimental group

Description:

Participants will be randomized to receive a single dose of different dose levels of VX-828.

Treatment:

Drug: VX-828

Drug: VX-828

Part A: Placebo

Placebo Comparator group

Description:

Participants will be randomized to receive placebo matched to VX-828.

Treatment:

Drug: Placebo

Drug: Placebo

Part B: Multiple Ascending Dose (MAD)

Experimental group

Description:

Participants will be randomized to receive multiple doses of different dose levels of VX-828. The dose levels will be determined based on the data from Part A.

Treatment:

Drug: VX-828

Drug: VX-828

Part B: Placebo

Placebo Comparator group

Description:

Participants will be randomized to receive placebo matched to VX-828.

Treatment:

Drug: Placebo

Drug: Placebo

Part C: Drug Drug Interaction

Experimental group

Description:

Participants will receive a single dose of VX-828, followed by a washout period, Itraconazole administration, and concomitant administration of itraconazole and VX-828; or participants will receive Midazolam followed by VX-828/TEZ/D-IVA administration, and concomitant administration of VX-828/TEZ/D-IVA and Midazolam. Part C will be an open-label optional cohort.

Treatment:

Drug: Tezacaftor

Drug: Deutivacaftor

Drug: Itraconazole

Drug: VX-828

Drug: Midazolam

Drug: VX-828

Part D: VX-828 in Triple Combination (TC) with TEZ/VX-118 or TEZ/D-IVA

Experimental group

Description:

Participants will be randomized to receive VX-828 in TC with TEZ/VX-118 or TEZ/D-IVA.

Treatment:

Drug: Tezacaftor

Drug: Deutivacaftor

Drug: VX-828

Drug: VX-828

Drug: VX-118

Part D: Placebo

Placebo Comparator group

Description:

Participants will be randomized to receive placebo matched to VX-828/TEZ/VX-118 or placebo matched to VX-828 in TC with TEZ/D-IVA.

Treatment:

Drug: Tezacaftor

Drug: Deutivacaftor

Drug: Placebo

Drug: Placebo

Part E: VX-828 in Combination with D-IVA with or without TEZ in CF

Experimental group

Description:

Participants with cystic fibrosis will receive VX-828 in combination with D-IVA with or without TEZ.

Treatment:

Drug: Tezacaftor

Drug: Deutivacaftor

Drug: VX-828

Drug: VX-828