A Phase 1/2 Study of VX-522 in Participants With Cystic Fibrosis (CF)

Phase 1

Recruiting

• Conditions: Cystic Fibrosis
• Interventions: Drug: VX-522 mRNA therapy; Drug: IVA

• Registration Number: NCT05668741
• Lead Sponsor: Vertex Pharmaceuticals Incorporated

Brief Summary

The purpose of this study is to evaluate the safety, and tolerability and efficacy of VX-522 in participants 18 years of age and older with cystic fibrosis and a cystic fibrosis transmembrane conductance regulator (CFTR) genotype not responsive to CFTR modulator therapy.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-12-19
• Study First Submitted QC: 2022-12-19
• Study First Posted: 2022-12-30
• Study Start: 2023-02-27
• Status Verified: 2025-09
• Last Update Submitted: 2025-11-18
• Last Update Posted: 2025-11-19
• Primary Completion: 2026-12-23
• Study Completion: 2027-05-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 39

Inclusion Criteria

• Body mass index is less than (<) 30.0 kilograms per meter square (kg/m^2)

• A total body weight greater than (>) 50 kg

• Stable CF disease

• CFTR gene mutations on both alleles that are not responsive to CFTR modulator therapy

  o Example mutations include but are not limited to, mutations that do not produce CFTR protein (i.e., Class I): nonsense mutations (e.g., G542X, W1282X) and canonical splice mutations (e.g., 621+1G->T)

• Forced expiratory volume in 1 second (FEV1) value for SAD: greater than or equal to (≥)40 percent (%), MAD: ≥ 40% to less than or equal to (≤) 90%

Key

Exclusion Criteria

• History of uncontrolled asthma within a year prior to screening
• History of solid organ or hematological transplantation
• Hepatic cirrhosis with portal hypertension, moderate hepatic impairment (Child Pugh Score 7 to 9), or severe hepatic impairment (Child Pugh Score 10 to 15)
• Arterial oxygen saturation on room air less than (<) 94% at screening

Other protocol defined Inclusion/Exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Single Ascending Dose (SAD)	VX-522 mRNA therapy	Participants grouped into different cohorts will receive a single ascending dose of VX-522.
Multiple Ascending Dose (MAD) Cohort 1: VX-522	VX-522 mRNA therapy	Participants will receive multiple ascending doses of VX-522.
MAD Cohort 1: VX-522+ IVA	VX-522 mRNA therapy	Following run-in period with ivacaftor (IVA), participants will receive multiple ascending doses of VX-522 with IVA.
MAD Cohort 1: VX-522+ IVA	IVA	Following run-in period with ivacaftor (IVA), participants will receive multiple ascending doses of VX-522 with IVA.
MAD Cohort 2: VX-522+ IVA	VX-522 mRNA therapy	Following run-in period with ivacaftor (IVA), participants will receive multiple ascending doses of VX-522 with IVA.
MAD Cohort 2: VX-522+ IVA	IVA	Following run-in period with ivacaftor (IVA), participants will receive multiple ascending doses of VX-522 with IVA.

Primary Outcome Measures

Name	Time	Method
Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	From Day 1 Through Week 8 [SAD and MAD]

Secondary Outcome Measures

Name	Time	Method
MAD: Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)	From Baseline at Day 29
MAD: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	From Day 1 Through Safety Follow-up Visit [up to Week 28]

Trial Locations

Locations (42)

University of Alabama at Birmingham - Child Health Research Unit; 🇺🇸 Birmingham, Alabama, United States

Memorial Health Services on behalf of Long Beach Memorial Medical Center d/b/a Miller Children's Hospital Long Beach; 🇺🇸 Long Beach, California, United States

Stanford University - Palo Alto - Pulmonology; 🇺🇸 Palo Alto, California, United States

National Jewish Health; 🇺🇸 Denver, Colorado, United States

Shands Hospital - Pulmonology; 🇺🇸 Gainesville, Florida, United States

Northwestern Memorial Hospital - Feinberg Pavilion; 🇺🇸 Chicago, Illinois, United States

Clinical & Translational Science Unit (CTSU) - Pulmonology; 🇺🇸 Kansas City, Kansas, United States

PAREXEL International - Baltimore; 🇺🇸 Baltimore, Maryland, United States

The Johns Hopkins University - Johns Hopkins Hospital - Pulmonology; 🇺🇸 Baltimore, Maryland, United States

MGH - MGfC Pediatric Cystic Fibrosis Center; 🇺🇸 Boston, Massachusetts, United States

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