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

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Parkinson's Disease
• Intervention / Treatment: Biological: VY-AADC02; Other: Sham (Placebo) Surgery

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Irvine, California, United States, 92697
      • UC Irvine
    • Sacramento, California, United States, 95817
      • UC Davis Health System
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Medical Faculty Foundation
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • New York
    • New York, New York, United States, 10017
      • NYU Langone Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Clinical Trials Management Office
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • University of Philadelphia, Dept of Neurology
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center (UPMC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III score in the OFF state	Baseline to Day 360
Change in MDS-UPDRS II score	Baseline to Day 360

Other Outcome Measures

Outcome Measure	Time Frame
Safety outcome measured by treatment emergent adverse events (TEAEs), serious adverse events (SAEs), changes in vital signs and clinical laboratory analysis, and immunogenicity	Baseline to Day 360

Collaborators and Investigators

• Sponsor: Neurocrine Biosciences
• Collaborators: Voyager Therapeutics
• Investigators: Study Director: Clinical Development Lead, Neurocrine Biosciences

Publications and helpful links

General Publications

• McFarthing K, Prakash N, Simuni T. CLINICAL TRIAL HIGHLIGHTS: 1. GENE THERAPY FOR PARKINSON'S, 2. PHASE 3 STUDY IN FOCUS - INTEC PHARMA'S ACCORDION PILL, 3. CLINICAL TRIALS RESOURCES. J Parkinsons Dis. 2019;9(2):251-264. doi: 10.3233/JPD-199001. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2018
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): November 1, 2024

Study Registration Dates

• First Submitted: May 16, 2018
• First Submitted That Met QC Criteria: June 7, 2018
• First Posted (Actual): June 19, 2018

Study Record Updates

• Last Update Posted (Actual): December 15, 2023
• Last Update Submitted That Met QC Criteria: December 8, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Gene Therapy; Dopamine; AAV; Levodopa; Neurosurgery; Parkinson's Disease (PD); AADC; DDC; Motor Fluctuations; Aromatic L-Amino Acid Decarboxylase; VY-AADC02; AAV2-hAADC; NBIb-1817
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: PD-1105

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No