A Study of the Safety and Efficacy of Prime Editing (PM577) in Participants With Wilson Disease (WD) (PM577a)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Wilson Disease; Wilson's Disease; Wilsons Disease
• Intervention / Treatment: Drug: PM577a

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 Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• New Zealand
  • Auckland
    • Grafton, Auckland, New Zealand, 1010
      • New Zealand Clinical Research (NZCR)
      • Contact: Ed Gane, MD; Email: liberty.auckland@nzcr.co.nz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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
• 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:

  1. Known or suspected active systemic infection
  2. Receipt of systemic antimicrobial therapy within 30 days of screening.
  3. 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:

  1. Clinical evidence of unstable coronary disease as defined by history of myocardial infarction in the past 24 months, history of unstable angina
  2. 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PM577a; 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).	Drug: PM577a; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability of PM577a. Quantified by frequency and severity of treatment emergent adverse events (TEAEs).	Post-infusion through Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency and severity of Dose Limiting Toxicities (DLTs)		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.		Infusion through Week 48
Percent of participants with non-ceruloplasmin bound copper (NCC)		Weeks 12, 24, and 48 post-infusion
Percent change from baseline in ceruloplasmin levels		From PM577a infusion to Weeks 4, 6, 9, 12, 24, and 48 post-infusion
Percent of participants with ceruloplasmin within the normal range		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)		Weeks 12, 24, and 48 post-infusion of PM577a
Change in serum radiocopper ratio		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)	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		Weeks 12 and 48 post-infusion of PM577a
On-target editing	Measured by liver biopsy specimen	Weeks 24 and 48 post-infusion
Percent change in Liver Copper Concentration	Assessed by liver biopsy	From baseline to Week 24, and to Week 48 post PM577a infusion
Change in Liver Stiffness	Measured using transient or shear wave elastography	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)	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.	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 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 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 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 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	From baseline to Weeks 12, 24, and 48 post PM577a infusion

Collaborators and Investigators

• Sponsor: Prime Medicine, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: July 24, 2026
• First Submitted That Met QC Criteria: July 31, 2026
• First Posted (Actual): August 5, 2026

Study Record Updates

• Last Update Posted (Actual): August 11, 2026
• Last Update Submitted That Met QC Criteria: August 10, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: gene therapy; gene editing; H1069Q; Prime Editing; PM577a
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Digestive System Diseases; Neurodegenerative Diseases; Liver Diseases; Movement Disorders; Heredodegenerative Disorders, Nervous System; Basal Ganglia Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Metal Metabolism, Inborn Errors; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Hepatolenticular Degeneration
• Other Study ID Numbers: Prime-0201; 2025-525034-62 (EudraCT Number)

Drug and device information, study documents

• 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.: Yes