A Clinical Trial of CAP-003 Gene Therapy in Adult Patients With GBA1 Associated Parkinson's Disease

A Phase 1/2 Dose-Escalation Trial to Evaluate Safety, Tolerability, and Efficacy of a Single Dose of CAP-003 Gene Therapy Administered to Patients With Parkinson's Disease With GBA1 Gene Mutation (PD-GBA)

The goal of this clinical trial is to learn about the safety of CAP-003 gene therapy in adults with GBA1 associated Parkinson's Disease. It will also provide information about whether CAP-003 demonstrates efficacy in these adults.

Participants will have a single intravenous infusion of CAP-003 and visit the clinic regularly for 2 years for checkups and tests.

This is a Phase 1/2, first-in-human, open-label, multi-centre, dose escalation trial to assess the safety, tolerability, and efficacy of a single intravenous (IV) dose of CAP-003 administered to adult patients aged 21 to 75 with Parkinson's Disease associated with GBA1 mutation.

Approximately 31 participants will be dosed in this trial. Phase 1 is a dose escalation phase that will dose approximately 6 participants divided into 2 cohorts (Cohort 1 and Cohort 2) while Phase 2 will have 1 dose cohort and dose approximately 25 participants. Participants in Phase 1 will be dosed sequentially in each cohort. Phase 2 will allow participants to be dosed concurrently if safety and tolerability data from Phase 1 are deemed acceptable.

Participants will receive a single IV infusion of CAP-003 and will then be followed for 2 years with safety measures, assessments to measure changes from Baseline in motor and non-motor scales, cognitive function, patient and clinical global impression of severity and improvement, disease progression, sleep scale and suicide severity rating.

Upon completion of the study or at the participant's final visit they will be invited to participate in a 3 year safety follow up study.

Inclusion Criteria:

• Male or female, 21 to 75 years
• Has diagnosis of Parkinson's disease (PD) per UK Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria;
• Has modified Hoehn and Yahr Stage I to III in the 'OFF' state;
• Presence of a pathogenic or likely pathogenic GBA1 mutation confirmed;
• Must be generally ambulatory, not dependent on wheelchair;
• Has a body weight of ≥40 kg (88 lb) to ≤110 kg (242 lb) and a body mass index (BMI) of 18 to 34 kg/m2;
• Participant has a reliable study partner/informant (eg, family member, friend) willing and able to participate in the trial as a source of information on the participant's health status and cognitive and functional abilities;
• Is living in the community (ie not in a nursing home)

Exclusion Criteria:

• Presence of a bi-allelic GBA1 mutation, or presence of LRRK2 2019S or other LRRK2 mutation;
• Diagnosis of significant central nervous system (CNS) disease other than PD that may be a cause for the participant's PD symptoms or may confound study objectives;
• Montreal Cognitive Assessment (MoCA) score of ≤22;
• History of deep brain stimulator placement, focused ultrasound therapy, or other intercranial surgery for PD;
• Hypersensitivity or contraindications to corticosteroid;
• Prior gene or cell therapy;
• Positive test result for anti-capsid total antibodies (tAb);
• Unable to undergo lumbar puncture;
• Diagnosis of Gaucher disease;
• Clinically significant abnormalities in safety lab tests, vital signs;
• Other illnesses or medications that may affect the interpretation of the study results.