VY-AADC02 for Parkinson's Disease With Motor Fluctuations (RESTORE-1)

Study Overview
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Brief Summary
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The objective of this study is to assess the safety of VY-AADC02 in participants with Parkinson's disease (PD) with motor fluctuations.

Official Title
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A Randomized, Sham Surgery Controlled, Double-blind, Multi-center, Phase 1 Clinical Trial, Evaluating the Safety of VY-AADC02 in Moderate to Advanced Parkinson's Disease Patients With Motor Fluctuations

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Biological: VY-AADC02
* Other: Sham (Placebo) Surgery


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Males and females, 40 to 75 years of age (inclusive) Diagnosis of PD, consistent with United Kingdom Brain Bank Criteria Motor responsiveness to dopaminergic therapy, demonstrated by improvement in Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS III score) Disease duration from diagnosis of ≥4 years An average of ≥3 hours of OFF time (that is, periods of insufficient control of motor PD symptoms) per day over 3 consecutive days as confirmed by the PD Diary A stable, optimal regimen of Parkinson's medications including levodopa for at least weeks prior to screening evaluation. Participants must have a minimum duration of levodopa treatment of ≥1 year In the judgment of the Investigator, stable Parkinson's features and symptoms for at least 4 weeks prior to screening evaluation Agrees to defer any elective neurological surgery, including deep brain stimulation or ablation procedure for PD, levodopa or apomorphine infusion, or the addition of new dopaminergic formulations until after the study is completed, if medically appropriate Ability to travel to study visits Key Exclusion Criteria: Atypical or secondary parkinsonism, including but not limited to symptoms believed to be due to trauma, brain tumor, infection, cerebrovascular disease, other neurological disease, or to drugs, chemicals, or toxins, as determined by the Investigator Montreal Cognitive Assessment (MoCA) score <26 New or unstable psychiatric conditions (psychosis, depression) within 1 year of screening Brain imaging abnormalities in the striatum or other regions that would substantially increase risk of surgery Contraindication to magnetic resonance imaging (MRI) and/or gadolinium-based contrast agents Prior brain surgery, infusion therapies or planned treatments that could complicate the study procedure or negatively impact study evaluations as determined from participant interview, screening MRI, or medical records History of malignancy other than treated carcinoma in situ within 3 years of screening evaluation Prior gene transfer, current treatment with any investigational agent (drug or device) within 2 months of screening evaluation, or participation or plans to participate in another research study Severe, biphasic and/or uncontrolled dyskinesia Disabling or uncontrolled impulse control disorders

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 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: Randomized, Sham Surgery Controlled, Double-blind, Multi-center
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VY-AADC02 (NBIb-1817)<br>Single administration of up to 3.6 x 10^12 vector genomes (vg) of VY-AADC02 | Biological: VY-AADC02<br>* Adeno-associated viral vector serotype 2 encoding human aromatic L-amino acid decarboxylase (AAV2- hAADC) infusion into the brain<br>|
| Placebo Comparator: Sham (Placebo) Surgery<br>Sham surgical procedure | Other: Sham (Placebo) Surgery<br>* Bilateral partial burr/twist holes without dura penetration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-emergent adverse events (TEAEs) |  | Up to 5 years after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AADC, Parkinson's Disease (PD), Aromatic L-Amino Acid Decarboxylase, AAV, VY-AADC02, AAV2-hAADC, DDC, Gene Therapy, Levodopa, Dopamine, Neurosurgery, NBIb-1817, Motor Fluctuations