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

A Phase 1/2 Dose Escalation Study Evaluating the Safety, and Tolerability and Efficacy of VX-522 in Subjects 18 Years of Age and Older With Cystic Fibrosis and a CFTR Genotype Not Responsive to CFTR Modulator Therapy

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: IVA; Drug: VX-522 mRNA therapy

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 (Actual): 26
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Melbourne, Australia
    • The Alfred Hospital - Pulmonology
• Belgium
  • Ghent, Belgium
    • Universitair Ziekenhuis Gent
• Canada
  • Calgary, Canada
    • University of Calgary Medical Clinic of the Foothills Medical Centre
  • Québec, Canada
    • IUCPQ Pavillon Recherche U-1771
• Germany
  • Essen, Germany
    • Ruhrlandklinik
• Sweden
  • Stockholm, Sweden
    • Karolinska University Hospital - Pulmonology
• United Kingdom
  • Cambridge, United Kingdom
    • Papworth Hospital NHS Foundation Trust
  • Glasgow, United Kingdom
    • Queen Elizabeth University Hospital - Pulmonology
  • London, United Kingdom
    • Royal Brompton Hospital
  • Manchester, United Kingdom
    • Wythenshawe Hospital - OPD
  • Penarth, United Kingdom
    • All Wales Adult Cystic Fibrosis Centre, University Hospital Llandough
  • Southampton, United Kingdom
    • University Hospital Southampton NHS Fountion - Southampton General Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham - Child Health Research Unit
  • California
    • Long Beach, California, United States, 90806
      • Memorial Health Services on behalf of Long Beach Memorial Medical Center d/b/a Miller Children's Hospital Long Beach
    • Palo Alto, California, United States, 94304
      • Stanford University - Palo Alto - Pulmonology
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Clinical & Translational Science Unit (CTSU) - Pulmonology
  • Maryland
    • Baltimore, Maryland, United States, 21225
      • PAREXEL International - Baltimore
    • Baltimore, Maryland, United States, 21287
      • The Johns Hopkins University - Johns Hopkins Hospital - Pulmonology
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
    • Boston, Massachusetts, United States, 02114
      • MGH - MGfC Pediatric Cystic Fibrosis Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota -Pulmonology
  • Missouri
    • St Louis, Missouri, United States, 63110
      • St. Louis Children's Hospital - Pulmonology
  • Ohio
    • Cincinnati, Ohio, United States, 45220
      • UC Health Holmes Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina - Pulmonology
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Hospital - Pulmonology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key 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: ≥ 50% 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Ascending Dose (SAD); Participants grouped into different cohorts will receive a single ascending dose of VX-522.	Drug: VX-522 mRNA therapy; Oral inhalation using nebulizer.
Experimental: Multiple Ascending Dose (MAD) Cohort 1: VX-522; Participants will receive multiple ascending doses of VX-522.	Drug: VX-522 mRNA therapy; Oral inhalation using nebulizer.
Experimental: MAD Cohort 1: VX-522+ IVA; Following run-in period with ivacaftor (IVA), participants will receive multiple ascending doses of VX-522 with IVA.	Drug: IVA; Tablet for oral administration.; Other Names: VX-770; ivacaftor; Drug: VX-522 mRNA therapy; Oral inhalation using nebulizer.
Experimental: MAD Cohort 2: VX-522+ IVA; Following run-in period with ivacaftor (IVA), participants will receive multiple ascending doses of VX-522 with IVA.	Drug: IVA; Tablet for oral administration.; Other Names: VX-770; ivacaftor; Drug: VX-522 mRNA therapy; Oral inhalation using nebulizer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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]

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated
• Collaborators: Moderna, Inc

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2023
• Primary Completion (Actual): April 21, 2026
• Study Completion (Estimated): September 9, 2026

Study Registration Dates

• First Submitted: December 19, 2022
• First Submitted That Met QC Criteria: December 19, 2022
• First Posted (Actual): December 30, 2022

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 20, 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; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Chloride Channel Agonists; ivacaftor
• Other Study ID Numbers: VX21-522-001; 2022-000726-25 (EudraCT Number); 2023-504786-23-00 (Other Identifier: EU CT Number)

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.: Yes