Treatment for Gaucher Disease with LY3884961

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)

This study is testing a new treatment called LY3884961 to see if it is safe and effective for adults with Gaucher Disease.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Prevail Therapeutics (Industry-sponsored)
• Locations: 8 sites (Chicago, Illinois and 7 other locations)
• Trial ID: NCT05487599 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and tolerability of LY3884961 in adults with peripheral manifestations of Gaucher Disease. It is a Phase 1/2, multicenter, open-label, dose-finding study that will assess up to three dose levels of the treatment in small cohorts of patients. Participants will be monitored for safety, immunogenicity, biomarkers, and efficacy over a duration of approximately five years, including a follow-up period after initial dosing.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18-65 with bi-allelic GBA1 mutations who have been on enzyme replacement therapy or substrate reduction therapy for at least two years.

Not a fit: Patients with significant neurological symptoms or active bone disease requiring surgical intervention may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve the management of Gaucher Disease and enhance the quality of life for affected patients.

How similar studies have performed: While this approach is novel, similar studies targeting Gaucher Disease have shown promise in the past, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

1. Age greater or equal to 18 years at the time of informed consent.
2. Bi-allelic pathogenic GBA1 variants 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, tissue and organ donation; and must agree to abstain from tissue and organ donation for the duration of the study, including long-term follow-up.

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 magnetic resonance imaging (MRI)
5. Evidence of clinically significant liver disease, fragile liver, or history of exposure to hepatotoxins.
6. Thrombocytopenia with platelet count \< 40 × 10\^3 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/or Check-in) 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 MRI, including claustrophobia or the presence of contraindicated metal (ferromagnetic)implants/cardiac pacemaker.

Where this trial is running

Chicago, Illinois and 7 other locations

• Ann and Robert H Lurie Children's Hospital of Chicago — Chicago, Illinois, United States (Recruiting)
• Duke University Health System — Durham, North Carolina, United States (Recruiting)
• Lysosomal & Rare Disorders Research and Treatment Center — Fairfax, Virginia, United States (Recruiting)
• Westmead Hospital-Cnr Hawkesbury and Darcy Rds — Westmead, New South Wales, Australia (Completed)
• Hospital de Clinicas de Porto Alegre (HCPA) — Porto Alegre, Rio Grande do Sul, Brazil (Recruiting)
• SphinCS Clinical Science for LSD — Höchheim, Germany (Recruiting)
• Hospital Quironsalud Zaragoza, Paseo Mariano Renovales Sn — Zaragoza, Spain (Recruiting)
• Royal Free Hospital NHS Trust — London, United Kingdom (Recruiting)

Study contacts

• Study coordinator: Prevail Therapeutics

Conditions Gaucher Disease; Gaucher Disease, Type 1