Prevail Therapeutics' PR001 Gene Therapy Trial for Parkinson's Disease Progresses

Prevail Therapeutics查看公司主页, a subsidiary of Eli Lilly查看公司主页 and Company, is advancing its Phase 1/2a PROPEL clinical trial (NCT04127578查看临床试验) to evaluate PR001查看药品详情 (LY3884961), an investigational adeno-associated virus serotype 9 (AAV9) vector-based gene therapy, for Parkinson's disease (PD) patients with at least one mutation in the GBA1 (搜索)搜索该靶点 gene.

PROPEL Trial Design and Objectives

The PROPEL trial is a multicenter, open-label, ascending dose study initiated on January 3, 2020. The trial is designed to assess the safety and efficacy of two different doses of PR001查看药品详情 administered as a one-time treatment, along with six intravenous pulses of methylprednisolone over three months. Sirolimus may be used if methylprednisolone is not well-tolerated. The trial aims to enroll a total of 20 patients and has an estimated completion date of June 2029. Currently, the study is recruiting participants at centers in Colorado, Florida, New York, and Pennsylvania. A center in Chicago, Illinois, is listed as active but not recruiting, and several centers in Israel have completed their participation.

Endpoints and Assessments

The primary endpoints of the PROPEL trial include the cumulative number of treatment-emergent adverse events (TEAEs) and serious AEs over a 5-year period, as well as the incidence of procedure-related AEs or TEAEs as measured by brain MRI, spine MRI, and nerve conduction studies, also over 5 years. Additional primary endpoints involve assessing the TE immunogenicity of AAV9, glucocerebrosidase (GCase), and neurofilament light chain (NfL) in the blood and of AAV9 and GCase in the cerebrospinal fluid (CSF) through 24 months post-treatment. Changes from baseline in the immunogenicity of AAV9, GCase, and NfL in the blood through 24 months and of AAV9 and GCase in the CSF through 12 months are also being evaluated.

Secondary endpoints include changes in glycolipid, GCase, and enzyme activity levels in the blood and CSF at various time points post-treatment (7 days, 14 days, 21 days, 1 month, 1.5 months, 2 months, 3 months, 6 months, 9 months, and 12 months).

Inclusion and Exclusion Criteria

Eligible participants are those diagnosed with PD according to the UK Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria, aged 35 to 80 years, weighing between 88 and 242 lbs, with a BMI of 18 to 34 kg/m2, and having at least one pathogenic mutation in GBA1 (搜索)搜索该靶点. They must also be Hoehn and Yahr Stage III-IV in the Practically Defined OFF state. Additional criteria include a negative test for Mycobacterium tuberculosis, general ambulation, stable use of background medications for at least 8 weeks before PR001查看药品详情 treatment, a reliable study partner/informant, up-to-date cancer screenings, non-residence in a nursing home, and recent pneumococcal and shingles vaccinations.

Exclusion criteria include significant central nervous system (CNS) diseases other than PD that could confound the study, a Montreal Cognitive Assessment score below 14, contraindications to intracisternal injection, clinically significant laboratory test abnormalities, hypersensitivity or contraindications to corticosteroids or sirolimus, prior deep brain stimulator placement, focused ultrasound, or surgery for PD, prior cell or gene therapy, recent live vaccines, ambroxol use, contraindications to imaging methods or anesthesia, participation in other disease-modifying PD clinical trials within 3 months, and any condition that could interfere with the study or pose an unacceptable safety risk.

Broader Context and Future Directions

Prevail Therapeutics查看公司主页 is also investigating PR001查看药品详情 for type 2 Gaucher disease (搜索)搜索该疾病 (G2D), also linked to the GBA1 (搜索)搜索该靶点 gene, in the Phase 1/2 PROVIDE clinical trial (NCT04411654查看临床试验).