A Study to Evaluate Efficacy and Safety of VX-864 in Participants With the PiZZ Genotype

A Phase 2, Open-label Study Evaluating Efficacy and Safety of VX-864 in Subjects With Alpha-1 Antitrypsin Deficiency Who Have the PiZZ Genotype, Over 48 Weeks

The purpose of this study evaluates the efficacy and safety of VX-864 in participants with the PiZZ genotype over 48 weeks.

Study Overview

• Status: Terminated
• Conditions: Alpha-1 Antitrypsin Deficiency
• Intervention / Treatment: Drug: VX-864

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Aachen, Germany
    • University Hospital RWTH Aachen
• Ireland
  • Beaumont, Ireland
    • Royal College of Surgeons in Ireland Clinical Research Centre, Beaumont Hospital
• United Kingdom
  • London, United Kingdom
    • King's College Hospital
• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Orlando, Florida, United States, 32803
      • Central Florida Pulmonary Group, P.A.
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • The University of Iowa Hospitals and Clinics: Adult Pulmonary Clinic
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Missouri
    • Hannibal, Missouri, United States, 63401
      • Hannibal Regional Healthcare System
  • New York
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27517
      • Marsico Clinical Research Center at UNC Pulmonary Clinic
  • Texas
    • Houston, Texas, United States, 77380
      • Renovatio Clinical
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah Health
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Medical Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Participants must have a PiZZ genotype confirmed at screening
• Plasma AAT levels indicating severe deficiency at screening

Key Exclusion Criteria:

• History of a medical condition that could negatively impact the ability to complete the study
• Solid organ, or hematological transplantation or is currently on a transplant list
• History of use of gene therapy or Ribonucleic acid interference (RNAi) therapy at any time previously
• Participants for whom discontinuation of augmentation therapy is not considered to be in their best interest, based on the clinical judgement of the treating physician

Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; Participants received VX-864 every 12 hours (q12h) for 48 weeks or until study drug dosing was terminated.	Drug: VX-864; Tablets for oral administration.
Experimental: Group B; Participants undergo a liver biopsy before receiving VX-864 q12h for 48 weeks or until study drug dosing was terminated, and undergo a second liver biopsy at either Week 24 or Week 48.	Drug: VX-864; Tablets for oral administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Blood Functional Alpha-1 Antitrypsin (AAT) Levels	From Baseline at Week 48

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in Blood Functional AAT Levels	From Baseline up to Week 48
Change in Blood Antigenic AAT Levels	From Baseline up to Week 48
Change in Blood Z-polymer Levels	From Baseline up to Week 48
Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Day 1 up to Week 52
Group B: Change in Z-polymer Accumulation in the Liver	From Baseline up to Week 48

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2023
• Primary Completion (Actual): August 19, 2024
• Study Completion (Actual): August 19, 2024

Study Registration Dates

• First Submitted: November 29, 2022
• First Submitted That Met QC Criteria: November 29, 2022
• First Posted (Actual): December 8, 2022

Study Record Updates

• Last Update Posted (Estimated): September 8, 2025
• Last Update Submitted That Met QC Criteria: August 19, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Liver Diseases; Subcutaneous Emphysema; Emphysema; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; alpha 1-Antitrypsin Deficiency
• Other Study ID Numbers: VX22-864-108; 2022-002746-40 (EudraCT 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/independent-research/clinical-trial-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