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

NCT06154447 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: VX23-828-001
• Study Type: interventional
• Target: 165
• Locations: 1 country
• Sites: 12

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).

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (8)

• 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 111)

• 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 Outcomes (11)

• 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)

Study Arms (8)

Part A: Single Ascending Dose (SAD)

EXPERIMENTAL

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

Drug: VX-828

Part A: Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Part B: Multiple Ascending Dose (MAD)

EXPERIMENTAL

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.

Drug: VX-828

Part B: Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Part C: Drug Drug Interaction

EXPERIMENTAL

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.

Drug: VX-828; Drug: Itraconazole; Drug: Midazolam; Drug: Tezacaftor; Drug: Deutivacaftor

Part D: VX-828 in combination with TEZ/VX-118 ,TEZ/D-IVA or D-IVA

EXPERIMENTAL

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

Drug: VX-828; Drug: Tezacaftor; Drug: VX-118; Drug: Deutivacaftor

Part D: Placebo

PLACEBO COMPARATOR

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

Drug: Tezacaftor; Drug: Placebo; Drug: Deutivacaftor

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

EXPERIMENTAL

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

Drug: Tezacaftor; Drug: Deutivacaftor; Drug: VX-828

Interventions

VX-828 DRUG

Suspension for Oral Administration

Part A: Single Ascending Dose (SAD); Part B: Multiple Ascending Dose (MAD); Part C: Drug Drug Interaction; Part D: VX-828 in combination with TEZ/VX-118 ,TEZ/D-IVA or D-IVA

Placebo DRUG

Suspension for Oral Administration

Part A: Placebo; Part B: Placebo

Midazolam DRUG

Syrup for Oral Administration

Part C: Drug Drug Interaction

Tezacaftor DRUG

Tablets for Oral Administration

Also known as: TEZ, VX-661

Part C: Drug Drug Interaction; Part D: Placebo; Part D: VX-828 in combination with TEZ/VX-118 ,TEZ/D-IVA or D-IVA; Part E: VX-828 in Combination with D-IVA with or without TEZ in CF

VX-118 DRUG

Tablets for Oral Administration

Part D: VX-828 in combination with TEZ/VX-118 ,TEZ/D-IVA or D-IVA

Deutivacaftor DRUG

Tablets for Oral Administration

Also known as: D-IVA, VX-561

Part C: Drug Drug Interaction; Part D: Placebo; Part D: VX-828 in combination with TEZ/VX-118 ,TEZ/D-IVA or D-IVA; Part E: VX-828 in Combination with D-IVA with or without TEZ in CF

Itraconazole DRUG

Solution for Oral Administration

Part C: Drug Drug Interaction

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead

Study Sites (12)

Joe DiMaggio Cycstic Fibrosis & Pulmonary Center

Hollywood, Florida, 33021, United States

Location

AdventHealth Medical Group Pulmonology at Orlando Ridgewood

Orlando, Florida, 32803, United States

Location

Altasciences Clinical Kansas

Overland Park, Kansas, 66212, United States

Location

Kentucky Children's Hospital

Lexington, Kentucky, 40508, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Minnesota -Pulmonology

Minneapolis, Minnesota, 55455, United States

Location

Billings Clinic, Pediatric Pulmonary Dept.

Billings, Montana, 59101, United States

Location

New York Medical College

Hawthorne, New York, 10532, United States

Location

ProMedica Toledo Children's Hospital & ProMedica Central Physicians, LLC

Toledo, Ohio, 43606, United States

Location

Cook Children's Pulmonology

Fort Worth, Texas, 76104, United States

Location

University of Utah Hospital - Pulmonology

Salt Lake City, Utah, 84132, United States

Location

Vermont Lung Center

Colchester, Vermont, 05446, United States

Location

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Itraconazole; Midazolam; tezacaftor; deutivacaftor, tezacaftor , vanzacaftor

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2023
• First Posted: December 4, 2023
• Study Start: December 12, 2023
• Primary Completion (Estimated): July 16, 2026
• Study Completion (Estimated): July 16, 2026
• Last Updated: May 26, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (12)