A study to improve the delivery of AAV2-GDNF and gadoteridol into the brain for patients with Parkinson's disease

The primary objective is to evaluate the optimization of AB-1005 intraputaminal administration using a prescriptive infusion algorithm (PIA) via convection-enhanced delivery (CED). In Stage 1, the investigation focuses on consistent delivery under intraoperative magnetic resonance imaging (iMRI) monitoring. Stage 2 aims to validate the success of PIA-based infusion using an operating room-based workflow integrated with a standard stereotactic platform without iMRI guidance. This study is classified under therapy.

• Assess the safety and tolerability of PIA-based intraputaminal delivery of AB-1005 through 6 months post-surgery in patients with Parkinson's disease.

This study involves 12 participants diagnosed with Parkinson's disease. The study population includes both male and female patients. Eligible individuals are between the ages of 45 and 75 years. Inclusion requires a diagnosis duration exceeding 10 years and a Modified Hoehn and Yahr stage of III-IV during an OFF state. Clinical requirements include the presence of bradykinesia alongside rigidity, resting tremor, or postural instability. Participants must demonstrate a Movement Disorder Society Unified Parkinson’s Disease Rating Scale Part III score greater than 40 in the OFF state and a reduction of at least 30% following a levodopa challenge. A stable anti-PD medication regimen for no more than 4 weeks is required.

This open-label, multi-stage Phase 2 study aims to optimize the intraputaminal administration of AAV2-GDNF using a prescriptive infusion algorithm (PIA). The research is divided into two distinct stages: Stage 1 utilizes interventional magnetic resonance imaging (iMRI) monitoring to investigate PIA-based infusion via convection-enhanced delivery (CED), while Stage 2 evaluates the success of the PIA-based infusion without iMRI monitoring using an operating room-based workflow and a standard stereotactic platform. The primary endpoint is the end-of-infusion volumetric putaminal coverage as assessed by MRI. Secondary endpoints include the duration of the surgical procedure, accuracy of cannula tip placement, neurological examinations, and immunological responses to the viral vector or glial cell line-derived neurotrophic factor. The study includes a screening phase to assess eligibility based on Parkinson's disease diagnosis, motor symptoms, and medication stability, followed by the surgical intervention and a long-term follow-up. Participant involvement includes the initial screening, the administration of the solution for injection, and subsequent follow-up visits to monitor adverse events and clinical outcomes.

The experimental treatment consists of AAV2-GDNF, an adeno-associated viral vector serotype 2 encoding glial cell line-derived neurotrophic factor. This substance is prepared as a solution for injection and is administered via intraputaminal use at a dose of 12,000,000,000,000.

The auxiliary treatment involves gadoteridol, provided as ProHance. This solution for injection is administered through intraputaminal use at a dosage of 8 µmol.

The primary efficacy endpoint for this study is the end-of-infusion volumetric putaminal coverage, which is evaluated using MRI during both Stage 1 and Stage 2. Secondary endpoints include the duration of surgical procedure, the change in total volumetric putaminal coverage within 60 to 120 minutes from the end of infusion in Stage 1, and the accuracy of cannula tip placement at the first and last targeted infusion stops in the putamen.

Further assessment involves the following parameters for Stage 1 and Stage 2:

• MoCA score
• BDI-II score
• C-SSRS
• Vital sign parameters
• Neurological and physical examinations
• Clinical laboratory measures
• Neuroimaging findings
• Immunological responses to AAV2 and/or GDNF
• Incidence and severity of adverse events, including SAEs, TEAEs related to the device, surgical procedure, or study drug