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

Vertex Pharmaceuticals

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Cystic Fibrosis

Treatments: Drug: IVA; Drug: VX-522 mRNA therapy

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT05668741

2023-504786-23-00 (Other Identifier)

2022-000726-25 (EudraCT Number)

VX21-522-001

Details and patient eligibility

About

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.

Enrollment: 33 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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: ≥ 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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33 participants in 3 patient groups

Single Ascending Dose (SAD)

Experimental group

Description:

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

Treatment:

Drug: VX-522 mRNA therapy

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

Experimental group

Description:

Participants grouped into different cohorts will receive multiple ascending doses of VX-522 in treatment arm 1 (T1).

Treatment:

Drug: VX-522 mRNA therapy

MAD Arm 2: VX522+ IVA

Experimental group

Description:

Following run-in period with ivacaftor (IVA), participants grouped into different cohorts will receive multiple ascending doses of VX-522 with IVA in treatment arm (T2).

Treatment:

Drug: VX-522 mRNA therapy

Drug: IVA