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

2026. szeptember 28. frissítette: Prime Medicine, Inc.

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.

A tanulmány áttekintése

Állapot

Toborzás

Körülmények

Beavatkozás / kezelés

Részletes leírás

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.

Tanulmány típusa

Beavatkozó

Beiratkozás (Becsült)

42

Fázis

  • 2. fázis
  • 1. fázis

Kapcsolatok és helyek

Ez a rész a vizsgálatot végzők elérhetőségeit, valamint a vizsgálat lefolytatásának helyére vonatkozó információkat tartalmazza.

Tanulmányi helyek

  • Egyesült Államok
    • Connecticut
      • New Haven, Connecticut, Egyesült Államok, 06510
    • Illinois
      • Chicago, Illinois, Egyesült Államok, 60611
        • Még nincs toborzás
        • Northwestern University Division of Gastroenterology and Hepatology
        • Kapcsolatba lépni:
    • Texas
      • San Antonio, Texas, Egyesült Államok, 78215
        • Toborzás
        • ARC Texas Liver Institute
        • Kapcsolatba lépni:
        • Kapcsolatba lépni:
  • Új Zéland
    • Auckland
      • Grafton, Auckland, Új Zéland, 1010
        • Toborzás
        • New Zealand Clinical Research (NZCR)
        • Kapcsolatba lépni:

Részvételi kritériumok

A kutatók olyan embereket keresnek, akik megfelelnek egy bizonyos leírásnak, az úgynevezett jogosultsági kritériumoknak. Néhány példa ezekre a kritériumokra a személy általános egészségi állapota vagy a korábbi kezelések.

Jogosultsági kritériumok

Tanulmányozható életkorok

12 év és régebbi (Gyermek, Felnőtt, Idősebb felnőtt)

Egészséges önkénteseket fogad

Nem

Tanulmányozható nemek

Összes

Leírás

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).

Tanulási terv

Ez a rész a vizsgálati terv részleteit tartalmazza, beleértve a vizsgálat megtervezését és a vizsgálat mérését.

Hogyan készül a tanulmány?

Tervezési részletek

  • Elsődleges cél: Kezelés
  • Kiosztás: N/A
  • Beavatkozó modell: Egyetlen csoportos hozzárendelés
  • Maszkolás: Nincs (Open Label)

Fegyverek és beavatkozások

Résztvevő csoport / kar
Beavatkozás / kezelés
Kísérleti: 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).
Drog: 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.

Mit mér a tanulmány?

Elsődleges eredményintézkedések

Eredménymérő
Időkeret
Safety and tolerability of PM577a. Quantified by frequency and severity of treatment emergent adverse events (TEAEs).
Időkeret: Post-infusion through Week 48
Post-infusion through Week 48

Másodlagos eredményintézkedések

Eredménymérő
Intézkedés leírása
Időkeret
Frequency and severity of Dose Limiting Toxicities (DLTs)
Időkeret: Infusion through the 14-day post infusion DLT observation period
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.
Időkeret: Infusion through Week 48
Infusion through Week 48
Percent of participants with non-ceruloplasmin bound copper (NCC)
Időkeret: Weeks 12, 24, and 48 post-infusion
Weeks 12, 24, and 48 post-infusion
Percent change from baseline in ceruloplasmin levels
Időkeret: From PM577a infusion to Weeks 4, 6, 9, 12, 24, and 48 post-infusion
From PM577a infusion to Weeks 4, 6, 9, 12, 24, and 48 post-infusion
Percent of participants with ceruloplasmin within the normal range
Időkeret: Weeks 4, 6, 9, 12, 24, and 48 post-infusion
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)
Időkeret: Weeks 12, 24, and 48 post-infusion of PM577a
Weeks 12, 24, and 48 post-infusion of PM577a
Change in serum radiocopper ratio
Időkeret: 24 hours/2 hours post-64Cu injection from baseline to Week 6 or later post-infusion of PM577a
24 hours/2 hours post-64Cu injection from baseline to Week 6 or later post-infusion of PM577a
Percentage of participants off of standard of care
Időkeret: Weeks 12 and 48 post-infusion of PM577a
Weeks 12 and 48 post-infusion of PM577a
Percent change in liver copper efflux
Időkeret: 1.5 hours and 20 hours post 64Cu injection from baseline to Week 6 or later post-infusion of PM577a

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
On-target editing
Időkeret: Weeks 24 and 48 post-infusion

Measured by liver biopsy specimen
Weeks 24 and 48 post-infusion
Percent change in Liver Copper Concentration
Időkeret: From baseline to Week 24, and to Week 48 post PM577a infusion

Assessed by liver biopsy
From baseline to Week 24, and to Week 48 post PM577a infusion
Change in Liver Stiffness
Időkeret: from baseline to Week 48 post PM577a infusion

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
Időkeret: From baseline through study completion (Week 48)

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
Időkeret: Week 48 post PM577a infusion compared to baseline

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)
Időkeret: Measured over the course of the study (through Week 48) compared to baseline

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)
Időkeret: Measured over the course of the study (through Week 48) compared to baseline

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
Időkeret: Measured at Week 48 post PM577a infusion compared to baseline

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
Időkeret: Measured at Week 48 post PM577a infusion compared to baseline

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)
Időkeret: From baseline to Weeks 12, 24, and 48 post PM577a infusion

For participants who are not on standard of care at the specified timepoint
From baseline to Weeks 12, 24, and 48 post PM577a infusion

Együttműködők és nyomozók

Itt találhatja meg a tanulmányban érintett személyeket és szervezeteket.

Szponzor

Prime Medicine, Inc.

Tanulmányi rekorddátumok

Ezek a dátumok nyomon követik a ClinicalTrials.gov webhelyre benyújtott vizsgálati rekordok és összefoglaló eredmények benyújtásának folyamatát. A vizsgálati feljegyzéseket és a jelentett eredményeket a Nemzeti Orvostudományi Könyvtár (NLM) felülvizsgálja, hogy megbizonyosodjon arról, hogy megfelelnek-e az adott minőség-ellenőrzési szabványoknak, mielőtt közzéteszik őket a nyilvános weboldalon.

Tanulmány főbb dátumok

Tanulmány kezdete (Becsült)

2026. szeptember 1.

Elsődleges befejezés (Becsült)

2028. november 1.

A tanulmány befejezése (Becsült)

2028. december 1.

Tanulmányi regisztráció dátumai

Először benyújtva

2026. július 24.

Először nyújtották be, amely megfelel a minőségbiztosítási kritériumoknak

2026. július 31.

Első közzététel (Tényleges)

2026. augusztus 5.

Tanulmányi rekordok frissítései

Utolsó frissítés közzétéve (Tényleges)

2026. október 1.

Az utolsó frissítés elküldve, amely megfelel a minőségbiztosítási kritériumoknak

2026. szeptember 28.

Utolsó ellenőrzés

2026. szeptember 1.

Több információ

A tanulmányhoz kapcsolódó kifejezések

Kulcsszavak

További vonatkozó MeSH feltételek

Egyéb vizsgálati azonosító számok

  • Prime-0201
  • 2025-525034-62 (EudraCT szám)
  • 2025 (Az Egyesült Államok NIH támogatása/szerződése)

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Igen

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