Evaluation of VX-828 in Healthy Participants and in Participants With Cystic Fibrosis
Phase 1
Recruiting
- Conditions
- Cystic Fibrosis
- Interventions
- Registration Number
- NCT06154447
- Lead Sponsor
- Vertex Pharmaceuticals Incorporated
- 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.).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 255
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A: Single Ascending Dose (SAD) VX-828 Participants will be randomized to receive a single dose of different dose levels of VX-828. Part A: Placebo Placebo Participants will be randomized to receive placebo matched to VX-828. Part B: Multiple Ascending Dose (MAD) VX-828 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. Part B: Placebo Placebo Participants will be randomized to receive placebo matched to VX-828. Part C: Drug Drug Interaction VX-828 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. Part C: Drug Drug Interaction Itraconazole 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. Part C: Drug Drug Interaction Midazolam 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. Part C: Drug Drug Interaction Tezacaftor 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. Part C: Drug Drug Interaction Deutivacaftor 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. Part D: VX-828 in Triple Combination (TC) with TEZ/VX-118 or TEZ/D-IVA VX-828 Participants will be randomized to receive VX-828 in TC with TEZ/VX-118 or TEZ/D-IVA. Part D: VX-828 in Triple Combination (TC) with TEZ/VX-118 or TEZ/D-IVA Tezacaftor Participants will be randomized to receive VX-828 in TC with TEZ/VX-118 or TEZ/D-IVA. Part D: VX-828 in Triple Combination (TC) with TEZ/VX-118 or TEZ/D-IVA VX-118 Participants will be randomized to receive VX-828 in TC with TEZ/VX-118 or TEZ/D-IVA. Part D: VX-828 in Triple Combination (TC) with TEZ/VX-118 or TEZ/D-IVA Deutivacaftor Participants will be randomized to receive VX-828 in TC with TEZ/VX-118 or TEZ/D-IVA. Part D: Placebo Tezacaftor 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. Part D: Placebo Placebo 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. Part D: Placebo Deutivacaftor 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. Part E: VX-828 in Combination with D-IVA with or without TEZ in CF Tezacaftor Participants with cystic fibrosis will receive VX-828 in combination with D-IVA with or without TEZ. Part E: VX-828 in Combination with D-IVA with or without TEZ in CF Deutivacaftor Participants with cystic fibrosis will receive VX-828 in combination with D-IVA with or without TEZ. Part E: VX-828 in Combination with D-IVA with or without TEZ in CF VX-828 Participants with cystic fibrosis will receive VX-828 in combination with D-IVA with or without TEZ.
- Primary Outcome Measures
Name Time Method Part A: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) From Signing of Informed Consent Form (ICF) up to Safety Follow Up (Up to Day 67) Part B: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) From Signing of Informed Consent Form (ICF) up to Safety Follow Up (Up to Day 80) Part D: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) From Signing of Informed Consent Form (ICF) up to Safety Follow Up (Up to Day 80) Part E: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) From Signing of Informed Consent Form (ICF) up to End of Study (Up to Day 83) Part C: Maximum Observed Concentration (Cmax) of VX-828 in Plasma in the Absence and Presence of Itraconazole From Day 1 up to Day 71 Part C: Area Under the Concentration Versus Time Curve (AUC) of VX-828 in Plasma in the Absence and Presence of Itraconazole From Day 1 up to Day 71 Part C: Maximum Observed Concentration (Cmax) of Midazolam in Plasma in the Absence and Presence of VX-828/TEZ/D-IVA From Day 1 up to Day 30 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 From Day 1 up to Day 30
- Secondary Outcome Measures
Name Time Method Part A: Maximum Observed Concentration (Cmax) of VX-828 in Plasma From Day 1 up to Day 67 Part A: Area Under the Concentration Versus Time Curve (AUC) of VX-828 in Plasma From Day 1 up to Day 67 Part B: Maximum Observed Concentration (Cmax) of VX-828 at Day 28 in Plasma From Day 1 up to Day 80 Part B: Area Under the Concentration Versus Time Curve (AUC) of VX-828 at Day 28 in Plasma From Day 1 up to Day 80 Part C: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) From Signing of Informed Consent Form (ICF) up to Safety Follow Up (Up to Day 82) Part D: Maximum Observed Concentration (Cmax) of VX-828, TEZ and D-IVA and their Metabolites at Day 28 in Plasma Day 28 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 Day 28 Part E: Maximum Observed Concentration (Cmax) of VX-828, TEZ, and D-IVA and their Metabolites in Plasma Day 1 and Day 28 Part E: Pre-dose Plasma Concentration (Ctrough) of VX-828, TEZ, D-IVA and its Metabolites Pre-dose at Day 4, Day 8, Day 15, Day 22, Day 35, Day 49, Day 63, Day 80 Part E: Area Under the Concentration Versus Time Curve (AUC) of VX-828, TEZ, and D-IVA and their Metabolites in Plasma Day 28 Part E: Absolute Change in Sweat Chloride From Baseline and At Day 28
Related Research Topics
Explore scientific publications, clinical data analysis, treatment approaches, and expert-compiled information related to the mechanisms and outcomes of this trial. Click any topic for comprehensive research insights.
What molecular mechanisms does VX-828 target in cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction?
How does VX-828's triple combination with Tezacaftor/VX-118 or D-IVA compare to standard-of-care CFTR modulators in clinical trials?
Which biomarkers are used to assess pharmacokinetics and response prediction in NCT06154447?
What are the potential adverse events associated with VX-828 and how are they managed in phase 1 trials?
How do Vertex Pharmaceuticals' CFTR modulators like VX-828 compare to competitor drugs in cystic fibrosis treatment?
Trial Locations
- Locations (1)
Altasciences Clinical Kansas
🇺🇸Overland Park, Kansas, United States
Altasciences Clinical Kansas🇺🇸Overland Park, Kansas, United States