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.
Inclusion Criteria:
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:
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:
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).
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).
Grafton, Auckland 1010, New Zealand
Prescreening Study to Identify Potential Wilson Disease Participants for Gene-Editing Clinical Trial
A Phase 1/2/3 Study of UX701 Gene Therapy in Adults With Wilson Disease
A Clinical Study to Evaluate the Safety and Efficacy of LY-M003 Injection in Patients With Wilson Disease
A Clinical Study on the Treatment of Wilson Disease With ATP7B mRNA/LNP (DSL101)
A Phase I/II Study of VTX-801 in Adult Patients With Wilson's Disease
Study of ALXN1840 Versus Standard of Care in Pediatric Participants With Wilson Disease