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

A Phase 1, Study of VX-828 in Healthy Subjects and in Subjects With Cystic Fibrosis

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).

Study Overview

• Status: Recruiting
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: VX-828; Drug: Placebo; Drug: Itraconazole; Drug: Midazolam; Drug: Placebo; Drug: Tezacaftor; Drug: VX-118; Drug: VX-828; Drug: Deutivacaftor

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.).

• Study Type: Interventional
• Enrollment (Estimated): 255
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Medical Information; Phone Number: 617-341-6777; Email: medicalinfo@vrtx.com

Study Locations

• United States
  • Florida
    • Hollywood, Florida, United States, 33021
      • Recruiting
      • Joe DiMaggio Cycstic Fibrosis & Pulmonary Center
    • Orlando, Florida, United States, 32803
      • Recruiting
      • AdventHealth Medical Group Pulmonology at Orlando Ridgewood
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Completed
      • Altasciences Clinical Kansas
  • Kentucky
    • Lexington, Kentucky, United States, 40508
      • Recruiting
      • Kentucky Children's Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Boston Children's Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • University of Minnesota -Pulmonology
  • Montana
    • Billings, Montana, United States, 59101
      • Recruiting
      • Billings Clinic, Pediatric Pulmonary Dept.
  • New York
    • Hawthorne, New York, United States, 10532
      • Recruiting
      • New York Medical College
  • Ohio
    • Toledo, Ohio, United States, 43606
      • Recruiting
      • ProMedica Toledo Children's Hospital & ProMedica Central Physicians, LLC
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Recruiting
      • Cook Children's Pulmonology
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Recruiting
      • University of Utah Hospital - Pulmonology
  • Vermont
    • Colchester, Vermont, United States, 05446
      • Recruiting
      • Vermont Lung Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: Single Ascending Dose (SAD); Participants will be randomized to receive a single dose of different dose levels of VX-828.	Drug: VX-828; Suspension for Oral Administration; Drug: VX-828; Tablets for Oral Administration
Placebo Comparator: Part A: Placebo; Participants will be randomized to receive placebo matched to VX-828.	Drug: Placebo; Suspension for Oral Administration; Drug: Placebo; Suspension and Tablets for Oral Administration
Experimental: Part B: Multiple Ascending Dose (MAD); 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; Suspension for Oral Administration; Drug: VX-828; Tablets for Oral Administration
Placebo Comparator: Part B: Placebo; Participants will be randomized to receive placebo matched to VX-828.	Drug: Placebo; Suspension for Oral Administration; Drug: Placebo; Suspension and Tablets for Oral Administration
Experimental: Part C: Drug Drug Interaction; 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; Suspension for Oral Administration; Drug: Itraconazole; Solution for Oral Administration; Drug: Midazolam; Syrup for Oral Administration; Drug: Tezacaftor; Tablets for Oral Administration; Other Names: VX-661; TEZ; Drug: VX-828; Tablets for Oral Administration; Drug: Deutivacaftor; Tablets for Oral Administration; Other Names: D-IVA; VX-561
Experimental: Part E: VX-828 in Combination with D-IVA with or without TEZ in CF; Participants with cystic fibrosis will receive VX-828 in combination with D-IVA with or without TEZ.	Drug: VX-828; Suspension for Oral Administration; Drug: Tezacaftor; Tablets for Oral Administration; Other Names: VX-661; TEZ; Drug: VX-828; Tablets for Oral Administration; Drug: Deutivacaftor; Tablets for Oral Administration; Other Names: D-IVA; VX-561
Experimental: Part D: VX-828 in combination with TEZ/VX-118 ,TEZ/D-IVA or D-IVA; Participants will be randomized to receive VX-828 in combination with TEZ/VX-118, TEZ/D-IVA, or D-IVA.	Drug: VX-828; Suspension for Oral Administration; Drug: Tezacaftor; Tablets for Oral Administration; Other Names: VX-661; TEZ; Drug: VX-118; Tablets for Oral Administration; Drug: VX-828; Tablets for Oral Administration; Drug: Deutivacaftor; Tablets for Oral Administration; Other Names: D-IVA; VX-561
Placebo Comparator: Part D: Placebo; 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: Placebo; Suspension for Oral Administration; Drug: Placebo; Suspension and Tablets for Oral Administration; Drug: Tezacaftor; Tablets for Oral Administration; Other Names: VX-661; TEZ; Drug: Deutivacaftor; Tablets for Oral Administration; Other Names: D-IVA; VX-561

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 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 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
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)

Secondary Outcome Measures

Outcome Measure	Time Frame
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: Area Under the Concentration Versus Time Curve (AUC) of VX-828, TEZ, and D-IVA and their Metabolites in Plasma	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: Absolute Change in Sweat Chloride	From Baseline and At Day 28

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2023
• Primary Completion (Estimated): April 23, 2026
• Study Completion (Estimated): April 23, 2026

Study Registration Dates

• First Submitted: November 23, 2023
• First Submitted That Met QC Criteria: November 23, 2023
• First Posted (Actual): December 4, 2023

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cystic Fibrosis; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azoles; Benzazepines; Benzodiazepines; Triazoles; Piperazines; Midazolam; Itraconazole; tezacaftor; deutivacaftor, tezacaftor , vanzacaftor
• Other Study ID Numbers: VX23-828-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/our-science/clinical-trials-data-sharing/

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No