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

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 atleast 3 months prior to screening.

4. Capable of giving signed informed consent, including compliance with therequirements and restrictions listed in the informed consent form (ICF) and in thisprotocol.

5. Females and males will be eligible for this study. Men and women of childbearingpotential must use a highly effective method of contraception consistently andcorrectly 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 ofthe study.

Exclusion Criteria:

1. Clinically significant neurological signs and symptoms and/or behavioraldisturbances.

2. Active and progressive bone disease expected to require surgical treatment in thenext 6 months.

3. History of total splenectomy or planned total splenectomy during the first 18 monthsof 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 ofexposure 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 conditionsbased on Investigator assessment.

9. History of certain cancers within 5 years of Screening.

10. Concomitant disease, condition or treatment which, in the opinion of theInvestigator, would pose an unacceptable risk to the patient or interfere with thepatient's ability to comply with study procedures or interfere with the conduct ofthe study.

11. Women of childbearing potential, pregnant (i.e., positive serum pregnancy result atScreening and Day 1) or breastfeeding or intending to become pregnant during thecourse of the trial.

12. Use of any GD-related chaperone therapy within 4 weeks prior to Screening orexpected need to initiate chaperone therapy during at least the first 18 months ofthe study.

13. Any type of prior gene or cell therapy.

14. Use of systemic immunosuppressant or steroid therapy other than protocol-specifiedimmunosuppression.

15. Participation in another therapeutic investigational drug or device study within 3months 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), includingclaustrophobia or the presence of contraindicated metal (ferromagnetic)implants/cardiac pacemaker.