a clinical trial of pr001 (ly3884961) in patients with peripheral manifestations of gaucher disease (proceed)

Conditions: Gaucher Disease; Gaucher Disease, Type 1

Summary: 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.


Eligibility criteria:
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.