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

Phase 1

Completed

• Conditions: Parkinson's Disease
• Interventions: Biological: VY-AADC02; Other: Sham (Placebo) Surgery

• Registration Number: NCT03562494
• Lead Sponsor: Neurocrine Biosciences

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-05-16
• Study First Submitted QC: 2018-06-07
• Study First Posted: 2018-06-19
• Study Start: 2018-10-17
• Primary Completion: 2024-10-30
• Study Completion: 2024-10-30
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-05
• Last Update Posted: 2024-12-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 14

Inclusion Criteria

1. Males and females, 40 to 75 years of age (inclusive)
2. Diagnosis of PD, consistent with United Kingdom Brain Bank Criteria
3. Motor responsiveness to dopaminergic therapy, demonstrated by improvement in Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS III score)
4. Disease duration from diagnosis of ≥4 years
5. 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
6. 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
7. In the judgment of the Investigator, stable Parkinson's features and symptoms for at least 4 weeks prior to screening evaluation
8. 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
9. Ability to travel to study visits

Key

Exclusion Criteria

1. 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
2. Montreal Cognitive Assessment (MoCA) score <26
3. New or unstable psychiatric conditions (psychosis, depression) within 1 year of screening
4. Brain imaging abnormalities in the striatum or other regions that would substantially increase risk of surgery
5. Contraindication to magnetic resonance imaging (MRI) and/or gadolinium-based contrast agents
6. 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
7. History of malignancy other than treated carcinoma in situ within 3 years of screening evaluation
8. 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
9. Severe, biphasic and/or uncontrolled dyskinesia
10. Disabling or uncontrolled impulse control disorders

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
VY-AADC02 (NBIb-1817)	VY-AADC02	Single administration of up to 3.6 x 10\^12 vector genomes (vg) of VY-AADC02
Sham (Placebo) Surgery	Sham (Placebo) Surgery	Sham surgical procedure

Primary Outcome Measures

Name	Time	Method
Number of participants with treatment-emergent adverse events (TEAEs)	Up to 5 years after surgery

Trial Locations

Locations (11)

UC Irvine; 🇺🇸 Irvine, California, United States

University of Philadelphia, Dept of Neurology; 🇺🇸 Philadelphia, Pennsylvania, United States

Northwestern Medical Faculty Foundation; 🇺🇸 Chicago, Illinois, United States

Ohio State University Clinical Trials Management Office; 🇺🇸 Columbus, Ohio, United States

University of Pittsburgh Medical Center (UPMC); 🇺🇸 Pittsburgh, Pennsylvania, United States

UC Davis Health System; 🇺🇸 Sacramento, California, United States

University of California, San Francisco; 🇺🇸 San Francisco, California, United States

University of Colorado; 🇺🇸 Aurora, Colorado, United States

Emory University Hospital; 🇺🇸 Atlanta, Georgia, United States

NYU Langone Medical Center; 🇺🇸 New York, New York, United States

University of Kansas Medical Center; 🇺🇸 Kansas City, Kansas, United States