A Study of the Safety and Efficacy of Prime Editing (PM577) in Participants With Wilson Disease (WD)
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age12+
SponsorPrime Medicine, Inc.
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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
Trial design
Design model
Single group
Treatments tested in this trial
PM577a
DrugPM577a 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.
Treatment groups
42 Participants
are divided into 1 treatment groupGroup A: PM577aExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Safety and tolerability of PM577a. Quantified by frequency and severity of treatment emergent adverse events (TEAEs).
Time frame
Post-infusion through Week 48Secondary outcomes
1
Frequency and severity of Dose Limiting Toxicities (DLTs)
Time frame
Infusion through the 14-day post infusion DLT observation period2
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 483
Percent of participants with non-ceruloplasmin bound copper (NCC)
Time frame
Weeks 12, 24, and 48 post-infusion4
Percent change from baseline in ceruloplasmin levels
Time frame
From PM577a infusion to Weeks 4, 6, 9, 12, 24, and 48 post-infusionSponsors and contacts
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Source ClinicalTrials.gov