Clinical trial NCT06154447: Evaluation of VX-828 in Healthy Participants and in Participants With Cystic Fibrosis
Official title: A Phase 1, Study of VX-828 in Healthy Subjects and in Subjects With Cystic Fibrosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2023-12-04
Enrollment: 255
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed 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.).

Eligibility 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.

Primary outcomes:
measure: Part A: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From Signing of Informed Consent Form (ICF) up to Safety Follow Up (Up to Day 67)
measure: Part B: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From Signing of Informed Consent Form (ICF) up to Safety Follow Up (Up to Day 80)
measure: Part D: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From Signing of Informed Consent Form (ICF) up to Safety Follow Up (Up to Day 80)
measure: Part E: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From Signing of Informed Consent Form (ICF) up to End of Study (Up to Day 83)
measure: Part C: Maximum Observed Concentration (Cmax) of VX-828 in Plasma in the Absence and Presence of Itraconazole
timeFrame: From Day 1 up to Day 71
measure: Part C: Area Under the Concentration Versus Time Curve (AUC) of VX-828 in Plasma in the Absence and Presence of Itraconazole
timeFrame: From Day 1 up to Day 71
measure: Part C: Maximum Observed Concentration (Cmax) of Midazolam in Plasma in the Absence and Presence of VX-828/TEZ/D-IVA
timeFrame: From Day 1 up to Day 30
measure: Part C: Area Under the Concentration Versus Time Curve (AUC) of Midazolam in Plasma in the Absence and Presence of VX-828/TEZ/D-IVA
timeFrame: From Day 1 up to Day 30
Secondary outcomes:
measure: Part A: Maximum Observed Concentration (Cmax) of VX-828 in Plasma
timeFrame: From Day 1 up to Day 67
measure: Part A: Area Under the Concentration Versus Time Curve (AUC) of VX-828 in Plasma
timeFrame: From Day 1 up to Day 67
measure: Part B: Maximum Observed Concentration (Cmax) of VX-828 at Day 28 in Plasma
timeFrame: From Day 1 up to Day 80
measure: Part B: Area Under the Concentration Versus Time Curve (AUC) of VX-828 at Day 28 in Plasma
timeFrame: From Day 1 up to Day 80
measure: Part C: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From Signing of Informed Consent Form (ICF) up to Safety Follow Up (Up to Day 82)
measure: Part D: Maximum Observed Concentration (Cmax) of VX-828, TEZ and D-IVA and their Metabolites at Day 28 in Plasma
timeFrame: Day 28
measure: Part D: Area Under the Concentration Versus Time Curve (AUC) of VX-828, TEZ and D-IVA and their Metabolites at Day 28 in Plasma
timeFrame: Day 28
measure: Part E: Maximum Observed Concentration (Cmax) of VX-828, TEZ, and D-IVA and their Metabolites in Plasma
timeFrame: Day 1 and Day 28
measure: Part E: Area Under the Concentration Versus Time Curve (AUC) of VX-828, TEZ, and D-IVA and their Metabolites in Plasma
timeFrame: Day 28
measure: Part E: Pre-dose Plasma Concentration (Ctrough) of VX-828, TEZ, D-IVA and its Metabolites
timeFrame: Pre-dose at Day 4, Day 8, Day 15, Day 22, Day 35, Day 49, Day 63, Day 80
measure: Part E: Absolute Change in Sweat Chloride
timeFrame: From Baseline and At Day 28
Other outcomes:
Locations:
city: Overland Park
country: United States
facility: Altasciences Clinical Kansas
state: Kansas
Study officials:
References: