NCT05643495

Brief Summary

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

Trial Health

60
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
14

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Feb 2023

Shorter than P25 for phase_2

Geographic Reach
4 countries

13 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 29, 2022

Completed
9 days until next milestone

First Posted

Study publicly available on registry

December 8, 2022

Completed
3 months until next milestone

Study Start

First participant enrolled

February 23, 2023

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 19, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 19, 2024

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

September 8, 2025

Completed
Last Updated

September 8, 2025

Status Verified

August 1, 2025

Enrollment Period

1.5 years

First QC Date

November 29, 2022

Results QC Date

August 19, 2025

Last Update Submit

August 19, 2025

Conditions

Alpha-1 Antitrypsin Deficiency

Outcome Measures

Primary Outcomes (1)

  • Change in Blood Functional Alpha-1 Antitrypsin (AAT) Levels

    From Baseline at Week 48

Secondary Outcomes (5)

  • 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

  • Group B: Change in Z-polymer Accumulation in the Liver

    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

Study Arms (2)

Group A

EXPERIMENTAL

Participants received VX-864 every 12 hours (q12h) for 48 weeks or until study drug dosing was terminated.

Drug: VX-864

Group B

EXPERIMENTAL

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

Interventions

VX-864DRUG

Tablets for oral administration.

Group AGroup B

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (13)

University of Florida

Gainesville, Florida, 32610, United States

Location

Central Florida Pulmonary Group, P.A.

Orlando, Florida, 32803, United States

Location

The University of Iowa Hospitals and Clinics: Adult Pulmonary Clinic

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Hannibal Regional Healthcare System

Hannibal, Missouri, 63401, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

Marsico Clinical Research Center at UNC Pulmonary Clinic

Chapel Hill, North Carolina, 27517, United States

Location

Renovatio Clinical

Houston, Texas, 77380, United States

Location

University of Utah Health

Salt Lake City, Utah, 84108, United States

Location

Inova Fairfax Medical Campus

Falls Church, Virginia, 22042, United States

Location

University Hospital RWTH Aachen

Aachen, Germany

Location

Royal College of Surgeons in Ireland Clinical Research Centre, Beaumont Hospital

Beaumont, Ireland

Location

King's College Hospital

London, United Kingdom

Location

MeSH Terms

Conditions

alpha 1-Antitrypsin Deficiency

Condition Hierarchy (Ancestors)

Liver DiseasesDigestive System DiseasesLung DiseasesRespiratory Tract DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesSubcutaneous EmphysemaEmphysemaPathologic ProcessesPathological Conditions, Signs and Symptoms

Results Point of Contact

Title
Medical Monitor
Organization
Vertex Pharmaceuticals Incorporated
medicalinfo@vrtx.com
617-341-6777

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 29, 2022

First Posted

December 8, 2022

Study Start

February 23, 2023

Primary Completion

August 19, 2024

Study Completion

August 19, 2024

Last Updated

September 8, 2025

Results First Posted

September 8, 2025

Record last verified: 2025-08

Data Sharing

IPD Sharing
Will not share

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

Locations

DE(1)US(10)GB(1)IE(1)