Prevail Therapeutics_J3Z-MC-OJAE

What is the Purpose of this Study?

Primary: To evaluate the safety and tolerability of LY3884961 Secondary: To evaluate the clinical and biomarker effects of LY3884961 on the following parameters, as outlined in the Schedule of Events: - Spleen volume - Platelet count - GluSph level in blood - ?-Glucocerebrosidase (GCase) enzyme activity and protein levels in blood - Time from LY3884961 administration to ERT/SRT discontinuation - Time from discontinuation of ERT/SRT to re-initiation of ERT/SRT Exploratory: To evaluate the effect of a single, IV infusion of LY3884961 on the following parameters: - Compliment Proteins - Anti-AAV9 ELISA - Anti-GCase ELISA - Anti-AAV9 ELISpot - Anti-GCase ELISpot Measure of GD activity (including hemoglobin level, liver volume, bone marrow involvement, bone mineral density, and lung function) - Biomarkers of lysosomal dysfunction and inflammation - Measures of quality of life and disease burden

Eligibility

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.

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.

Show less

Where can I participate?

Beverly

More about this Clinical Trial

What is the full name of this clinical trial?

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

Study Details

Disease Type/Condition

Other

Principal Investigator

Lorber, Jeremy

Age Group

Adult

Phase

I/II

IRB Number

STUDY00003096

ClinicalTrials.gov ID

NCT05487599

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

clinicaltrials@cshs.org