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

NCT05668741 | Active Not Recruiting Phase 1 FDA Drug

• 3 other identifiers: VX21-522-0012022-000726-252023-504786-23-00
• Study Type: interventional
• Target: 26
• Locations: 7 countries
• Sites: 26

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.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• 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]

Study Arms (4)

Single Ascending Dose (SAD)

EXPERIMENTAL

Participants grouped into different cohorts will receive a single ascending dose of VX-522.

Drug: VX-522 mRNA therapy

Multiple Ascending Dose (MAD) Cohort 1: VX-522

EXPERIMENTAL

Participants will receive multiple ascending doses of VX-522.

Drug: VX-522 mRNA therapy

MAD Cohort 1: VX-522+ IVA

EXPERIMENTAL

Following run-in period with ivacaftor (IVA), participants will receive multiple ascending doses of VX-522 with IVA.

Drug: VX-522 mRNA therapy; Drug: IVA

MAD Cohort 2: VX-522+ IVA

EXPERIMENTAL

Following run-in period with ivacaftor (IVA), participants will receive multiple ascending doses of VX-522 with IVA.

Drug: VX-522 mRNA therapy; Drug: IVA

Interventions

VX-522 mRNA therapy DRUG

Oral inhalation using nebulizer.

MAD Cohort 1: VX-522+ IVA; MAD Cohort 2: VX-522+ IVA; Multiple Ascending Dose (MAD) Cohort 1: VX-522; Single Ascending Dose (SAD)

IVA DRUG

Tablet for oral administration.

Also known as: ivacaftor, VX-770

MAD Cohort 1: VX-522+ IVA; MAD Cohort 2: VX-522+ IVA

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%

You may not qualify if:

• 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

Sponsors & Collaborators

• Moderna, Inc: collaborator
• Vertex Pharmaceuticals Incorporated: lead

Study Sites (26)

University of Alabama at Birmingham - Child Health Research Unit

Birmingham, Alabama, 35233, United States

Location

Memorial Health Services on behalf of Long Beach Memorial Medical Center d/b/a Miller Children's Hospital Long Beach

Long Beach, California, 90806, United States

Location

Stanford University - Palo Alto - Pulmonology

Palo Alto, California, 94304, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

Clinical & Translational Science Unit (CTSU) - Pulmonology

Kansas City, Kansas, 66160, United States

Location

PAREXEL International - Baltimore

Baltimore, Maryland, 21225, United States

Location

The Johns Hopkins University - Johns Hopkins Hospital - Pulmonology

Baltimore, Maryland, 21287, United States

Location

MGH - MGfC Pediatric Cystic Fibrosis Center

Boston, Massachusetts, 02114, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Minnesota -Pulmonology

Minneapolis, Minnesota, 55455, United States

Location

St. Louis Children's Hospital - Pulmonology

St Louis, Missouri, 63110, United States

Location

UC Health Holmes Hospital

Cincinnati, Ohio, 45220, United States

Location

Medical University of South Carolina - Pulmonology

Charleston, South Carolina, 29425, United States

Location

University of Utah Hospital - Pulmonology

Salt Lake City, Utah, 84132, United States

Location

The Alfred Hospital - Pulmonology

Melbourne, Australia

Location

Universitair Ziekenhuis Gent

Ghent, Belgium

Location

University of Calgary Medical Clinic of the Foothills Medical Centre

Calgary, Canada

Location

IUCPQ Pavillon Recherche U-1771

Québec, Canada

Location

Ruhrlandklinik

Essen, Germany

Location

Karolinska University Hospital - Pulmonology

Stockholm, Sweden

Location

Papworth Hospital NHS Foundation Trust

Cambridge, United Kingdom

Location

Queen Elizabeth University Hospital - Pulmonology

Glasgow, United Kingdom

Location

Royal Brompton Hospital

London, United Kingdom

Location

Wythenshawe Hospital - OPD

Manchester, United Kingdom

Location

All Wales Adult Cystic Fibrosis Centre, University Hospital Llandough

Penarth, United Kingdom

Location

University Hospital Southampton NHS Fountion - Southampton General Hospital

Southampton, United Kingdom

Location

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

ivacaftor

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2022
• First Posted: December 30, 2022
• Study Start: February 27, 2023
• Primary Completion: April 21, 2026
• Study Completion (Estimated): September 9, 2026
• Last Updated: May 22, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); SE (1); GB (6); CA (2); DE (1); US (14); BE (1)