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

• ClinicalTrials.gov Identifier: NCT05668741
• Recruitment Status: Recruiting
• First Posted: December 30, 2022
• Last Update Posted: May 9, 2024
• Sponsor: Vertex Pharmaceuticals Incorporated
• Collaborator: Moderna, Inc
• Information provided by (Responsible Party): Vertex Pharmaceuticals Incorporated

Tracking Information

• First Submitted Date: December 19, 2022
• First Posted Date: December 30, 2022
• Last Update Posted Date: May 9, 2024
• Actual Study Start Date: February 27, 2023
• Estimated Primary Completion Date: March 2025 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: March 12, 2024): Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From Day 1 Through Safety Follow-up Visit [up to Week 24 for SAD, and Week 28 for T1 and T2 (MAD)] ]
• Original Primary Outcome Measures (submitted: December 19, 2022): Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From Day 1 Through Safety Follow-up Visit (Week 24) ]

Current Secondary Outcome Measures (submitted: March 12, 2024)

• T1 (MAD): Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) [ Time Frame: From Baseline at Day 29 ]
• T2 (MAD): Change From Pre-Run-in Baseline in ppFEV1 [ Time Frame: From Pre-Run Baseline at Day 29 ]

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase 1/2 Study of VX-522 in Participants With Cystic Fibrosis (CF)
• Official Title: 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Cystic Fibrosis

Intervention

• Drug: VX-522 mRNA therapy
  Oral inhalation using nebulizer.
• Drug: IVA
  Tablet for oral administration.
  Other Names:

  • ivacaftor
  • VX-770

Study Arms

• Experimental: Single Ascending Dose (SAD)
  Participants grouped into different cohorts will receive a single ascending dose of VX-522.
  Intervention: Drug: VX-522 mRNA therapy
• Experimental: Multiple Ascending Dose (MAD) Arm 1
  Participants grouped into different cohorts will receive multiple ascending doses of VX-522 in treatment arm 1 (T1).
  Intervention: Drug: VX-522 mRNA therapy
• Experimental: MAD Arm 2: VX522+ IVA
  Following run-in period with ivacaftor (IVA), participants will receive multiple doses of VX-522 with IVA in treatment arm (T2).
  Interventions:

  • Drug: VX-522 mRNA therapy
  • Drug: IVA

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 12, 2024): 36
• Original Estimated Enrollment (submitted: December 19, 2022): 9
• Estimated Study Completion Date: March 2025
• Estimated Primary Completion Date: March 2025 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Medical Information; 617-341-6777; medicalinfo@vrtx.com

• Listed Location Countries: Australia, Canada, United Kingdom, United States

Administrative Information

• NCT Number: NCT05668741
• Other Study ID Numbers: VX21-522-001; 2022-000726-25 ( EudraCT Number ); 2023-504786-23-00 ( Other Identifier: EU CT Number )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/independent-research/clinical-trial-data-sharing

• Current Responsible Party: Vertex Pharmaceuticals Incorporated
• Original Responsible Party: Same as current
• Current Study Sponsor: Vertex Pharmaceuticals Incorporated
• Original Study Sponsor: Same as current
• Collaborators: Moderna, Inc
• Investigators: Not Provided
• PRS Account: Vertex Pharmaceuticals Incorporated
• Verification Date: April 2024