A Double-blind Study to Evaluate the Safety of Glutamic Acid Decarboxylase Gene Transfer in Parkinson's Participants

Study Overview
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Brief Summary
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The objective of this clinical trial is to evaluate the safety and tolerability of adeno-associated virus (AAV)-mediated delivery of glutamic acid decarboxylase (GAD) gene transfer into the subthalamic nuclei (STN) of participants with Parkinson's Disease.

Detailed Description
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The planned length of participation in the study for each participant will be approximately 7 months. This includes a screening period of up to 40 days, randomization and surgery, and a follow-up period of 26 weeks.

Official Title
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A Randomized, Double-Blind, Sham-Controlled Study to Evaluate the Safety and Tolerability of Glutamic Acid Decarboxylase Gene Transfer to the Subthalamic Nuclei in Participants With Parkinson's Disease

Conditions
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Parkinson Disease

Intervention / Treatment
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* Genetic: AAV-GAD Dose 1
* Genetic: AAV-GAD Dose 2
* Procedure: Sham Surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed Parkinson's Disease Levodopa responsiveness for at least 12 months UPDRS Part 3 score of ≥25 points in the off state Exclusion Criteria: Past history of brain surgery to treat Parkinson's Disease Any history of cerebral insult or central nervous system infection Atypical Parkinson's Disease Focal or lateralized neurologic deficits Evidence of significant medical or psychiatric disorders Cognitive impairment as defined by Montreal Cognitive Assessment (MoCA)≤20 Beck Depression Inventory-II score of ≥ 20

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants are enrolled in one of three groups in parallel for the duration of the study.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AAV-GAD Dose 1 treatment group<br>Eligible participants will receive bilateral infusion of AAV-GAD Dose 1 into the STN | Genetic: AAV-GAD Dose 1<br>* Bilateral infusion of AAV-GAD Dose 1<br>|
| Experimental: AAV-GAD Dose 2 treatment group<br>Eligible participants will receive bilateral infusion of AAV-GAD Dose 2 into the STN | Genetic: AAV-GAD Dose 2<br>* Bilateral infusion of AAV-GAD Dose 2<br>|
| Sham Comparator: Sham treatment group<br>Eligible participants will undergo a sham surgical procedure | Procedure: Sham Surgery<br>* Sham infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of AAV-GAD delivered to the STN in patients with Parkinson's Disease | Number of participants with adverse events and serious adverse events | Baseline to Week 26 |