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

Parkinson's Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03562494
• Other study ID #: PD-1105
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: October 17, 2018
• Est. completion date: November 2024

Study information

• Verified date: December 2023
• Source: Neurocrine Biosciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 14
• Est. completion date: November 2024
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

Key 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

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Biological:
• VY-AADC02
Adeno-associated viral vector serotype 2 encoding human aromatic L-amino acid decarboxylase (AAV2- hAADC) infusion into the brain

Other:
• Sham (Placebo) Surgery
Bilateral partial burr/twist holes without dura penetration

Locations

Country	Name	City	State
United States	Emory University Hospital	Atlanta	Georgia
United States	University of Colorado	Aurora	Colorado
United States	Northwestern Medical Faculty Foundation	Chicago	Illinois
United States	Ohio State University Clinical Trials Management Office	Columbus	Ohio
United States	UC Irvine	Irvine	California
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	NYU Langone Medical Center	New York	New York
United States	University of Philadelphia, Dept of Neurology	Philadelphia	Pennsylvania
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

Sponsors (2)

Lead Sponsor	Collaborator
Neurocrine Biosciences	Voyager Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with treatment-emergent adverse events (TEAEs)		Up to 5 years after surgery