Alpha-1 Antitrypsin DeficiencyPhase 2NCT05643495
A Study to Evaluate Efficacy and Safety of VX-864 in Participants With the PiZZ Genotype
A Phase 2 study testing VX-864 in people with Alpha-1 Antitrypsin Deficiency, run by Vertex Pharmaceuticals Incorporated at 13 sites in 4 countries.
Trial summary
The purpose of this study evaluates the efficacy and safety of VX-864 in participants with the PiZZ genotype over 48 weeks. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Alpha-1 Antitrypsin Deficiency
- What is being tested?
- VX-864
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 13 sitesin 4 countries
- Study dates
- 23 Feb 2023to 19 Aug 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must have a PiZZ genotype confirmed at screening
- Plasma AAT levels indicating severe deficiency at screening
Who cannot join
- 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.
Trial locations and contacts
13 sites in 4 countries.
13 sites in 4 countries
United States10 sites
Marsico Clinical Research Center at UNC Pulmonary Clinic
Chapel Hill, North Carolina, 27517
Inova Fairfax Medical Campus
Falls Church, Virginia, 22042
University of Florida
Gainesville, Florida, 32610
Hannibal Regional Healthcare System
Hannibal, Missouri, 63401
Renovatio Clinical
Houston, Texas, 77380
The University of Iowa Hospitals and Clinics: Adult Pulmonary Clinic
Iowa City, Iowa, 52242
University of Kansas Medical Center
Kansas City, Kansas, 66160
Columbia University Irving Medical Center
New York, New York, 10032
Central Florida Pulmonary Group, P.A.
Orlando, Florida, 32803
University of Utah Health
Salt Lake City, Utah, 84108
Ireland1 site
Royal College of Surgeons in Ireland Clinical Research Centre, Beaumont Hospital
Beaumont
About this study
Official title: 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.
- Conditions
- Alpha-1 Antitrypsin Deficiency
- Being tested
- VX-864
- Medical subject headings
- alpha 1-Antitrypsin Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VX-864Drug
Tablets for oral administration.
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | Participants received VX-864 every 12 hours (q12h) for 48 weeks or until study drug dosing was terminated. Receives: 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. Receives: Drug: VX-864 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Blood Functional Alpha-1 Antitrypsin (AAT) Levels
Measured: From Baseline at Week 48
Secondary outcomes (5)
Change in Blood Functional AAT Levels
Measured: From Baseline up to Week 48
Change in Blood Antigenic AAT Levels
Measured: From Baseline up to Week 48
Change in Blood Z-polymer Levels
Measured: From Baseline up to Week 48
Group B: Change in Z-polymer Accumulation in the Liver
Measured: From Baseline up to Week 48
Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measured: Day 1 up to Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2022
- Study start23 Feb 2023
- Primary completion19 Aug 2024
- Study completion19 Aug 2024
Why it stopped: Study drug dosing was permanently discontinued at the Sponsor's discretion based on frequency and nature of skin and subcutaneous tissue disorders.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alpha-1 Antitrypsin DeficiencyStudies of the same condition, open and under way.
- More trials run by Vertex Pharmaceuticals IncorporatedThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vertex Pharmaceuticals Incorporated
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05643495
- Sponsor's protocol ID
- VX22-864-108
- Other IDs
- 2022-002746-40
- Status last verified
- Aug 2025
- First submitted
- 29 Nov 2022
- Last updated
- 8 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: 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
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05643495
- Acronym / sponsor ID
- VX22-864-108
- Conditions
- Alpha-1 Antitrypsin Deficiency
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study drug dosing was permanently discontinued at the Sponsor's discretion based on frequency and nature of skin and subcutaneous tissue disorders.
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Vertex Pharmaceuticals IncorporatedIndustry (pharma, biotech, devices)
- Study start
- 23 Feb 2023 (actual)
- Primary completion
- 19 Aug 2024 (actual)
- Study completion
- 19 Aug 2024 (actual)
- First posted
- 8 Dec 2022 (actual)
- Results
- Posted 8 Sep 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study evaluates the efficacy and safety of VX-864 in participants with the PiZZ genotype over 48 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Drug: VX-864Participants received VX-864 every 12 hours (q12h) for 48 weeks or until study drug dosing was terminated. |
| Group B | Experimental | Drug: VX-864Participants 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Participants must have a PiZZ genotype confirmed at screening
- Plasma AAT levels indicating severe deficiency at screening
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VX-864Tablets for oral administration. | Drug | Group A, Group B |
Primary outcome
Change in Blood Functional Alpha-1 Antitrypsin (AAT) Levels
Time frame: From Baseline at Week 48
5 secondary outcomes
Change in Blood Functional AAT Levels
Time frame: From Baseline up to Week 48
Change in Blood Antigenic AAT Levels
Time frame: From Baseline up to Week 48
Change in Blood Z-polymer Levels
Time frame: From Baseline up to Week 48
Group B: Change in Z-polymer Accumulation in the Liver
Time frame: From Baseline up to Week 48
Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Day 1 up to Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
13 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing VX-864 in people with Alpha-1 Antitrypsin Deficiency, run by Vertex Pharmaceuticals Incorporated at 13 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States, Germany, Ireland, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Sep 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Blood Functional Alpha-1 Antitrypsin (AAT) Levels (time frame: From Baseline at Week 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Sep 2025.