A Clinical Trial of PR001 (LY3884961) in Patients With Peripheral Manifestations of Gaucher Disease (PROCEED)

An Open-label, Dose-Finding, Phase 1/2 Study to Evaluate the Safety and Tolerability of a Single Intravenous Dose of LY3884961 in Patients With Peripheral Manifestations of Gaucher Disease (PROCEED)

Study J3Z-MC-OJAE is a Phase 1/2, multicenter, open-label, dose-finding study of LY3884961 evaluating the safety and tolerability in adults with peripheral manifestations of GD.

Up to 3 dose levels of LY3884961 will be assessed in 3 dose-finding cohorts of 3 patients. Following this, up to 6 patients may be enrolled into an expansion cohort.

For each enrolled patient, the study will be approximately 5 years in duration, including up to a 45-day screening period. During the first 18 months after dosing, subjects will be evaluated for the effects of LY3884961 on safety, tolerability, immunogenicity, biomarkers, and efficacy. Patients will be followed up for an additional 42 months to monitor safety, immunogenicity, and selected biomarker and efficacy parameters.

Study Overview

• Status: Recruiting
• Conditions: Gaucher Disease; Gaucher Disease, Type 1
• Intervention / Treatment: Genetic: LY3884961

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Prevail Therapeutics; Phone Number: (917) 336-9310; Email: prevail.patients@lilly.com

Study Locations

• Spain
  • Madrid, Spain, 28034
    • Recruiting
    • Hospital Universitario Ramon y Cajal, Calle Colmenar Viejo Km 9100
    • Contact: Jesus Villarrubia; Phone Number: +34913368967; Email: jesus.villarrubia@salud.madrid.org
  • Zaragoza, Spain, 50006
    • Recruiting
    • Hospital Quironsalud Zaragoza, Paseo Mariano Renovales Sn
    • Contact: Teresa Navarro; Phone Number: +690762382; Email: teresanair@feeteg.org
• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710-3017
      • Recruiting
      • Duke University Health System
      • Contact: Gretchen Clinical Research Coordinator; Phone Number: 919-660-0757; Email: Gretchen.nichting@duke.edu
  • Virginia
    • Fairfax, Virginia, United States, 22030-6066
      • Recruiting
      • Lysosomal Rare Disorders Research and Treatment Center
      • Contact: Lauren Noll; Phone Number: 571-732-4655; Email: lnoll@ldrtc.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18-65 years inclusive at the time of informed consent.
2. Bi-allelic GBA1 mutations must be centrally confirmed.
3. On ERT or SRT for at least 2 years and on a stable, maximum tolerated dose, for at least 3 months prior to screening.
4. Capable of giving signed informed consent, including compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
5. Females and males will be eligible for this study. Men and women of childbearing potential must use a highly effective method of contraception consistently and correctly for the duration of the study, including the long-term follow-up.
6. Patients must agree to abstain from blood donations for at least the first year of the study.

Exclusion Criteria:

1. Clinically significant neurological signs and symptoms and/or behavioral disturbances.
2. Active and progressive bone disease expected to require surgical treatment in the next 6 months.
3. History of total splenectomy or planned total splenectomy during the first 18 months of the study. (Partial splenectomy not exclusionary).
4. Splenomegaly > 10 MN as evaluated by centrally read abdominal MRI
5. Evidence of clinically significant liver disease, fragile liver, or history of exposure to hepatotoxins.
6. Thrombocytopenia with platelet count < 40 × 103 per μL.
7. Severe hyperlipidemia (triglycerides > 1,000 mg/dL).
8. Current diagnosis of unstable or clinically significant cardiovascular conditions based on Investigator assessment.
9. History of certain cancers within 5 years of Screening.
10. Concomitant disease, condition or treatment which, in the opinion of the Investigator, would pose an unacceptable risk to the patient or interfere with the patient's ability to comply with study procedures or interfere with the conduct of the study.
11. Women of childbearing potential, pregnant (i.e., positive serum pregnancy result at Screening and Day 1) or breastfeeding or intending to become pregnant during the course of the trial.
12. Use of any GD-related chaperone therapy within 4 weeks prior to Screening or expected need to initiate chaperone therapy during at least the first 18 months of the study.
13. Any type of prior gene or cell therapy.
14. Use of systemic immunosuppressant or steroid therapy other than protocol-specified immunosuppression.
15. Participation in another therapeutic investigational drug or device study within 3 months or 5 half-lives of the study agent, whichever is longer.
16. Have an anti-AAV9 antibody titer of >1:40 as determined by central laboratory.
17. Clinically significant abnormalities in laboratory test results at Screening.
18. Have any contraindications for magnetic resonance imaging (MRI), including claustrophobia or the presence of contraindicated metal (ferromagnetic)implants/cardiac pacemaker.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY3884961; LY3884961 is an advanced therapy investigational medicinal product administered as a single intravenous infusion.	Genetic: LY3884961; • LY3884961 is a replication-incompetent recombinant adeno-associated virus (AAV) vector. The vector is composed of a ss DNA genome packaged in an AAV-derived protein capsid.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) with AE's graded as mild, moderate, or severe.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spleen volume	Change and percent change from baseline	5 years
Platelet count	Change from baseline	5 years
Discontinuation of enzyme replacement therapy (ERT)/substrate reduction therapy (SRT)	Time from dosing to discontinuation of ERT/SRT	5 years
Re-initiation of ERT/SRT (if necessary)	Time to re-initiation of ERT/SRT (if necessary) Time to re-initiation of ERT/SRT (if necessary)	5 years
GCase levels	Change from baseline	5 years
GluSph levels	Change from baseline	5 years

Collaborators and Investigators

• Sponsor: Prevail Therapeutics
• Collaborators: Eli Lilly and Company
• Investigators: Study Director: Sarah Neuhaus, DO, Prevail Therapeutics, a wholly owned subsidiary of Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2022
• Primary Completion (Estimated): October 2, 2030
• Study Completion (Estimated): October 2, 2030

Study Registration Dates

• First Submitted: June 1, 2022
• First Submitted That Met QC Criteria: August 1, 2022
• First Posted (Actual): August 4, 2022

Study Record Updates

• Last Update Posted (Actual): February 22, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Gene Therapy; glucocerebrosidase; Gaucher Disease; Gaucher; AAV9; GBA1 mutation; GBA; Type 1 Gaucher; bi-allelic glucocerebrosidase-1; GD1
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Lipidoses; Lipid Metabolism, Inborn Errors; Gaucher Disease; Physiological Effects of Drugs; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Prednisone; Sirolimus
• Other Study ID Numbers: J3Z-MC-OJAE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No