Wilson DiseasePhase 1/2PM577aNCT07748403
A Study of the Safety and Efficacy of Prime Editing (PM577) in Participants With Wilson Disease (WD)
A Phase 1/2 study testing PM577a in people with Wilson Disease and Wilson's Disease, run by Prime Medicine, Inc. at 4 sites in 2 countries.
Trial summary
The purpose of this study is to evaluate the safety, tolerability, biological activity, and initial efficacy of PM577a, an investigational Prime Editing therapy, in adults and adolescents with Wilson disease (WD). Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Wilson Disease, Wilson's Disease, Wilsons Disease
- What is being tested?
- PM577a
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 4 sitesin 2 countries
- Study dates
- Sep 2026to Dec 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Confirmed Wilson Disease (WD) diagnosis as determined by medical history consistent with WD
- Historical genetic analysis demonstrating biallelic pathogenic, likely pathogenic, or suspected pathogenic ATP7B variants, including at least one p.H1069Q allele.
- Treated and stable on standard of care therapy for WD for the past 6 months prior to signing ICF, as documented by a history of adherence to SOC medications (i.e., penicillamine, trientine, and/or zinc) without significant medication or dose/frequency changes, per Investigator judgement.
- Demonstrated Adequate Copper Control confirmed at screening
- Willingness to maintain a stable, copper-conscious diet and avoid copper-containing supplements, from signing of the ICF until the physician determines that it is no longer necessary post-infusion.
- Willingness to abstain from alcohol use from start of the screening period through 3 months after PM577a infusion and adhere to recommendations of moderate alcohol consumption (as defined in this protocol) through primary follow-up period.
- Participants are expected to enroll in a separate long-term follow-up study for a total of approximately 15 years of follow-up following PM577a administration.
Who cannot join
- Known prior medically significant reactions (e.g., severe hypersensitivity, myocarditis) to an LNP-based or PEG-containing product (e.g., mRNA-based COVID vaccinations, MiraLAX) or any medication required as part of the clinical study protocol
- Receipt of any prior gene therapy for WD, including AAV-based therapy
- Receipt of any liver-directed LNP gene therapy (including siRNA or ASO therapies) or gene editing treatment.
- Unstable neurological conditions within the prior 12 months which may impact participant safety or participation in the study, including ability to complete study requirements or procedures as outlined in the clinical study protocol in the opinion of the Investigator
- In individuals with psychiatric involvement, current or fluctuant clinical instability with new or changing diagnoses or substantial medication regimen changes in the past 12 months that could limit their participation, in the opinion of the Investigator.
- Receipt of prior liver transplantation or listed for transplantation
Show all 23Show fewer
- Body Mass Index ≥ 35 kg/m2
- Evidence of Severe Hepatic Impairment or uncontrolled liver disease within 6 months before screening.
- Evidence of Moderate or Severe Renal Impairment in the last year
- History of significant liver disease other than WD
- Clinically significant coagulopathy or disorder of platelet function
- Active infectious disease including:
- Known or suspected active systemic infection
- Receipt of systemic antimicrobial therapy within 30 days of screening.
- Positive for presence of human immunodeficiency virus (HIV)-1 or HIV-2 (evidence of infection, regardless of viral load).
- History of known autoimmune or genetic causes of myopathy or myositis
- Prior or current malignancy or myeloproliferative disorder (excluding Stage 1 or lower, fully treated/excised malignant and pre-malignant disease of the skin, cervix or colon. Additionally, any other malignant and pre-malignant disease that the Investigator in consultation with the treating oncologist and study Medical Monitor deem has been fully treated/excised for > 5 years).
- Any condition, laboratory abnormality, or reason that could adversely affect participant safety or study results, as determined by the Investigator, including, but not limited to:
- Clinical evidence of unstable coronary disease as defined by history of myocardial infarction in the past 24 months, history of unstable angina
- Any severe clinical condition of limited life expectancy
- Pregnancy or breastfeeding in a postpartum female or absence of adequate contraception for fertile participants. Females of childbearing potential and non-sterile male participants who are or may become sexually active with female partners of childbearing potential are required to use highly effective contraception from Screening through at least 84 days after drug product infusion.
- History of moderate or severe Alcohol Use Disorder (AUD) or Drug Use Disorder (DUD) with < 3 years of continuous abstinence preceding the date of screening
- Participation in another clinical study with an investigational drug within 30 days of Screening or at least 5 times the half-life of the investigational drug (whichever is longer).
Trial locations and contacts
4 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
4 sites in 2 countries
United States3 sites, 3 recruiting
- Not yet recruiting
Northwestern University Division of Gastroenterology and Hepatology
Chicago, Illinois, 60611
Amanda Cheung, MD, 312-695-8178, irene.coronaavila@northwestern.edu
- Not yet recruiting
Yale New Haven Hospital
New Haven, Connecticut, 06510
Michael Schilsky, 203-737-1592, michael.schilsky@yale.edu
Gunjan Kukreja, 203-737-3422, gunjan.kukreja@yale.edu
- Recruiting
ARC Texas Liver Institute
San Antonio, Texas, 78215
Eric Lawitz, MD, 210-253-3426, lawitz@txliver.com
Tolu Okubote, 210-890-5851, tokubote@txliver.com
New Zealand1 site, 1 recruiting
- Recruiting
New Zealand Clinical Research (NZCR)
Grafton, Auckland, 1010
Ed Gane, MD, + 64 9 373 3474 ext. 7031, liberty.auckland@nzcr.co.nz
About this study
Official title: A Phase 1/2 Clinical Study to Evaluate Safety, Tolerability, Biological Activity, and Initial Efficacy of Prime Editing (PM577a) for the Treatment of Wilson Disease (WD) in Adult and Adolescent Participants With at Least One Allele Harboring the p.H1069Q Mutation in ATP7B
The purpose of this study is to evaluate the safety, tolerability, biological activity, and initial efficacy of PM577a, an investigational Prime Editing therapy, in adults and adolescents with Wilson disease (WD).
Wilson disease is caused by changes (mutations) in the ATP7B gene that prevent the body from removing excess copper normally. PM577a is designed to precisely correct one of the most common disease-causing ATP7B mutations (p.H1069Q) in liver cells with the goal of restoring normal copper metabolism.
This is the first study of PM577a in people. Participants will receive a single intravenous (IV) infusion of PM577a and will be monitored closely to evaluate safety, how the body responds to treatment, whether copper metabolism improves, and whether treatment may improve signs and symptoms of Wilson disease.
Read the detailed description
This is a Phase 1/2, open-label study evaluating PM577a in adults and adolescents with Wilson disease who have specific disease-causing changes in the ATP7B gene, including at least one p.H1069Q mutation.
The study will evaluate the safety of PM577a, determine an appropriate dose for future studies, and assess whether treatment restores copper metabolism and improves clinical measures of Wilson disease. Participants will receive a single IV infusion of PM577a and will undergo regular safety evaluations, laboratory testing, imaging, and clinical assessments for approximately 48 weeks after treatment. Participants will then be asked to enroll in a separate long-term follow-up study to continue monitoring safety and treatment effects.
- Conditions
- Wilson Disease, Wilson's Disease, Wilsons Disease
- Being tested
- PM577a
- Keywords
- H1069Q, gene therapy, gene editing, Prime Editing, PM577a
- Medical subject headings
- Hepatolenticular Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PM577aDrug
PM577a is being evaluated in participants with Wilson disease caused by biallelic pathogenic, likely pathogenic, or suspected pathogenic ATP7B variants, including at least one p.H1069Q allele.
| Study group | Role | What they receive |
|---|---|---|
| PM577a | Experimental | PM577a is a sterile suspension of lipid nanoparticle (LNP)-formulated Prime Editors (PEs) intended for single dose intravenous (IV) infusion for the treatment of Wilson disease (WD). Receives: Drug: PM577a |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of PM577a. Quantified by frequency and severity of treatment emergent adverse events (TEAEs).
Measured: Post-infusion through Week 48
Secondary outcomes (19)
Frequency and severity of Dose Limiting Toxicities (DLTs)
Measured: Infusion through the 14-day post infusion DLT observation period
Evidence of improved copper metabolism based on meeting the criteria to stop standard of care (SOC) therapy (chelation or zinc), including stable or improving non-ceruloplasmin bound copper levels and liver function tests.
Measured: Infusion through Week 48
Percent of participants with non-ceruloplasmin bound copper (NCC)
Measured: Weeks 12, 24, and 48 post-infusion
Percent change from baseline in ceruloplasmin levels
Measured: From PM577a infusion to Weeks 4, 6, 9, 12, 24, and 48 post-infusion
Percent of participants with ceruloplasmin within the normal range
Measured: Weeks 4, 6, 9, 12, 24, and 48 post-infusion
Percent of participants with improved non-ceruloplasmin bound copper measured by protein speciation (NCC-Sp)
Measured: Weeks 12, 24, and 48 post-infusion of PM577a
Change in serum radiocopper ratio
Measured: 24 hours/2 hours post-64Cu injection from baseline to Week 6 or later post-infusion of PM577a
Percent change in liver copper efflux
Measured by hepatic 64Cu PET standard uptake value (SUV)
Measured: 1.5 hours and 20 hours post 64Cu injection from baseline to Week 6 or later post-infusion of PM577a
Percentage of participants off of standard of care
Measured: Weeks 12 and 48 post-infusion of PM577a
On-target editing
Measured by liver biopsy specimen
Measured: Weeks 24 and 48 post-infusion
Percent change in Liver Copper Concentration
Assessed by liver biopsy
Measured: From baseline to Week 24, and to Week 48 post PM577a infusion
Change in Liver Stiffness
Measured using transient or shear wave elastography
Measured: from baseline to Week 48 post PM577a infusion
Evaluation of health-related quality of life (HRQoL) as compared to baseline
Measured using the age-appropriate EuroQol 5 Dimension 5-Level instrument (EQ-5D-5L)
Measured: From baseline through study completion (Week 48)
Percent of participants with stable or improved modified Unified Wilson's Disease Rating Scale (mUWDRS) score
Test is divided into 3 parts to assess for neurological and functional status in Wilson disease and divided into 3 parts. Part 1 (range 0-3), Part 2a (range 0-40), Part 2b (range 0-20) and Part 3 (range 0-147). Total cumulative range is 0-210. Higher scores indicate greater disease severity.
Measured: Week 48 post PM577a infusion compared to baseline
Percent of participants with stable or improved score on the Clinical Global Impression Improvement Scale (CGI-I)
Scores range from 1-7. Lower scores indicate a better outcome.
Measured: Measured over the course of the study (through Week 48) compared to baseline
Percent of participants with stable or improved score on the Clinical Global Impression Severity Scale (CGI-S)
Scores range from 1-7. Lower scores indicate a better outcome.
Measured: Measured over the course of the study (through Week 48) compared to baseline
Percent of participants with stable or improved Model for End-Stage Liver Disease (MELD) score
Scores range from 6 and upward, with higher scores indicating a more severe liver disease and a worse prognosis.
Measured: Measured at Week 48 post PM577a infusion compared to baseline
Percent of participants with stable or improved modified Nazer score
This score assesses prognosis in Wilson disease using total bilirubin, international normalized ratio (INR), aspartate aminotransferase (AST), white blood cell count (WBC), and serum albumin. Each component is scored from 0 to 4, producing a total score ranging from 0 to 20. Higher scores indicate a worse prognosis.
Measured: Measured at Week 48 post PM577a infusion compared to baseline
Percent change in 24-hour urinary copper excretion (UCE)
For participants who are not on standard of care at the specified timepoint
Measured: From baseline to Weeks 12, 24, and 48 post PM577a infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2026
- Study startSep 2026 (estimated)
- Primary completionNov 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Wilson DiseaseStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Prime Medicine, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07748403
- Sponsor's protocol ID
- Prime-0201
- Other IDs
- 2025-525034-62, 2025
- Acronym
- PM577a
- Status last verified
- Sep 2026
- First submitted
- 24 Jul 2026
- Last updated
- 1 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Clinical Study to Evaluate Safety, Tolerability, Biological Activity, and Initial Efficacy of Prime Editing (PM577a) for the Treatment of Wilson Disease (WD) in Adult and Adolescent Participants With at Least One Allele Harboring the p.H1069Q Mutation in ATP7B
- ClinicalTrials.gov ID
- NCT07748403
- Acronym / sponsor ID
- PM577a / Prime-0201
- Conditions
- Wilson Disease, Wilson's Disease, Wilsons Disease
- Keywords
- H1069Q, gene therapy, gene editing, Prime Editing, PM577a
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- Prime Medicine, Inc.Industry (pharma, biotech, devices)
- Study start
- Sep 2026 (estimated)
- Primary completion
- Nov 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 5 Aug 2026 (actual)
- Results
- Not posted in the source record
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 is to evaluate the safety, tolerability, biological activity, and initial efficacy of PM577a, an investigational Prime Editing therapy, in adults and adolescents with Wilson disease (WD).
Wilson disease is caused by changes (mutations) in the ATP7B gene that prevent the body from removing excess copper normally. PM577a is designed to precisely correct one of the most common disease-causing ATP7B mutations (p.H1069Q) in liver cells with the goal of restoring normal copper metabolism.
This is the first study of PM577a in people. Participants will receive a single intravenous (IV) infusion of PM577a and will be monitored closely to evaluate safety, how the body responds to treatment, whether copper metabolism improves, and whether treatment may improve signs and symptoms of Wilson disease.
Detailed description
This is a Phase 1/2, open-label study evaluating PM577a in adults and adolescents with Wilson disease who have specific disease-causing changes in the ATP7B gene, including at least one p.H1069Q mutation.
The study will evaluate the safety of PM577a, determine an appropriate dose for future studies, and assess whether treatment restores copper metabolism and improves clinical measures of Wilson disease. Participants will receive a single IV infusion of PM577a and will undergo regular safety evaluations, laboratory testing, imaging, and clinical assessments for approximately 48 weeks after treatment. Participants will then be asked to enroll in a separate long-term follow-up study to continue monitoring safety and treatment effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PM577a | Experimental | Drug: PM577aPM577a is a sterile suspension of lipid nanoparticle (LNP)-formulated Prime Editors (PEs) intended for single dose intravenous (IV) infusion for the treatment of Wilson disease (WD). |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Confirmed Wilson Disease (WD) diagnosis as determined by medical history consistent with WD
- Historical genetic analysis demonstrating biallelic pathogenic, likely pathogenic, or suspected pathogenic ATP7B variants, including at least one p.H1069Q allele.
- Treated and stable on standard of care therapy for WD for the past 6 months prior to signing ICF, as documented by a history of adherence to SOC medications (i.e., penicillamine, trientine, and/or zinc) without significant medication or dose/frequency changes, per Investigator judgement.
- Demonstrated Adequate Copper Control confirmed at screening
- Willingness to maintain a stable, copper-conscious diet and avoid copper-containing supplements, from signing of the ICF until the physician determines that it is no longer necessary post-infusion.
Key exclusion criteria (23 listed)
- Known prior medically significant reactions (e.g., severe hypersensitivity, myocarditis) to an LNP-based or PEG-containing product (e.g., mRNA-based COVID vaccinations, MiraLAX) or any medication required as part of the clinical study protocol
- Receipt of any prior gene therapy for WD, including AAV-based therapy
- Receipt of any liver-directed LNP gene therapy (including siRNA or ASO therapies) or gene editing treatment.
- Unstable neurological conditions within the prior 12 months which may impact participant safety or participation in the study, including ability to complete study requirements or procedures as outlined in the clinical study protocol in the opinion of the Investigator
- In individuals with psychiatric involvement, current or fluctuant clinical instability with new or changing diagnoses or substantial medication regimen changes in the past 12 months that could limit their participation, in the opinion of the Investigator.
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 |
|---|---|---|
| PM577aPM577a is being evaluated in participants with Wilson disease caused by biallelic pathogenic, likely pathogenic, or suspected pathogenic ATP7B variants, including at least one p.H1069Q allele. | Drug | PM577a |
Primary outcome
Safety and tolerability of PM577a. Quantified by frequency and severity of treatment emergent adverse events (TEAEs).
Time frame: Post-infusion through Week 48
19 secondary outcomes
Frequency and severity of Dose Limiting Toxicities (DLTs)
Time frame: Infusion through the 14-day post infusion DLT observation period
Evidence of improved copper metabolism based on meeting the criteria to stop standard of care (SOC) therapy (chelation or zinc), including stable or improving non-ceruloplasmin bound copper levels and liver function tests.
Time frame: Infusion through Week 48
Percent of participants with non-ceruloplasmin bound copper (NCC)
Time frame: Weeks 12, 24, and 48 post-infusion
Percent change from baseline in ceruloplasmin levels
Time frame: From PM577a infusion to Weeks 4, 6, 9, 12, 24, and 48 post-infusion
Percent of participants with ceruloplasmin within the normal range
Time frame: Weeks 4, 6, 9, 12, 24, and 48 post-infusion
Percent of participants with improved non-ceruloplasmin bound copper measured by protein speciation (NCC-Sp)
Time frame: Weeks 12, 24, and 48 post-infusion of PM577a
Change in serum radiocopper ratio
Time frame: 24 hours/2 hours post-64Cu injection from baseline to Week 6 or later post-infusion of PM577a
Percent change in liver copper efflux
Time frame: 1.5 hours and 20 hours post 64Cu injection from baseline to Week 6 or later post-infusion of PM577a
Percentage of participants off of standard of care
Time frame: Weeks 12 and 48 post-infusion of PM577a
On-target editing
Time frame: Weeks 24 and 48 post-infusion
Percent change in Liver Copper Concentration
Time frame: From baseline to Week 24, and to Week 48 post PM577a infusion
Change in Liver Stiffness
Time frame: from baseline to Week 48 post PM577a infusion
Evaluation of health-related quality of life (HRQoL) as compared to baseline
Time frame: From baseline through study completion (Week 48)
Percent of participants with stable or improved modified Unified Wilson's Disease Rating Scale (mUWDRS) score
Time frame: Week 48 post PM577a infusion compared to baseline
Percent of participants with stable or improved score on the Clinical Global Impression Improvement Scale (CGI-I)
Time frame: Measured over the course of the study (through Week 48) compared to baseline
Percent of participants with stable or improved score on the Clinical Global Impression Severity Scale (CGI-S)
Time frame: Measured over the course of the study (through Week 48) compared to baseline
Percent of participants with stable or improved Model for End-Stage Liver Disease (MELD) score
Time frame: Measured at Week 48 post PM577a infusion compared to baseline
Percent of participants with stable or improved modified Nazer score
Time frame: Measured at Week 48 post PM577a infusion compared to baseline
Percent change in 24-hour urinary copper excretion (UCE)
Time frame: From baseline to Weeks 12, 24, and 48 post PM577a infusion
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2026.
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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.
Northwestern University Division of Gastroenterology and Hepatology
Chicago, United States
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing PM577a in people with Wilson Disease and Wilson's Disease, run by Prime Medicine, Inc. at 4 sites in 2 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 7 inclusion and 23 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: looking for participants now, as of the sponsor's last update on 1 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States, New Zealand. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability of PM577a. Quantified by frequency and severity of treatment emergent adverse events (TEAEs). (time frame: Post-infusion through 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 1 Oct 2026.