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

NCT07748403 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: Prime-02012025-525034-622025
• Study Type: interventional
• Target: 42
• Locations: 2 countries
• Sites: 4

Brief 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). 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.

Conditions

Wilson Disease; Wilsons Disease

Keywords

H1069Q; gene therapy; gene editing; Prime Editing; PM577a

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of PM577a. Quantified by frequency and severity of treatment emergent adverse events (TEAEs).

  Post-infusion through Week 48

Secondary Outcomes (19)

• 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

Study Arms (1)

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).

Drug: PM577a

Interventions

PM577a DRUG

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.

PM577a

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• 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).

Sponsors & Collaborators

• Prime Medicine, Inc.: lead

Study Sites (4)

Yale New Haven Hospital

New Haven, Connecticut, 06510, United States

NOT YET RECRUITING

Northwestern University Division of Gastroenterology and Hepatology

Chicago, Illinois, 60611, United States

NOT YET RECRUITING

ARC Texas Liver Institute

San Antonio, Texas, 78215, United States

RECRUITING

New Zealand Clinical Research (NZCR)

Grafton, Auckland, 1010, New Zealand

RECRUITING

MeSH Terms

Conditions

Hepatolenticular Degeneration

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Metal Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2026
• First Posted: August 5, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: October 1, 2026

Record last verified: 2026-09

Locations

NZ (1); US (3)