Clinical trial NCT03562494: VY-AADC02 for Parkinson's Disease With Motor Fluctuations (RESTORE-1)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Parkinson's Disease
Keywords: Parkinson's Disease (PD)
Aromatic L-Amino Acid Decarboxylase
AADC
AAV
VY-AADC02
AAV2-hAADC
DDC
Gene Therapy
Levodopa
Dopamine
Neurosurgery
NBIb-1817
Motor Fluctuations
Lead sponsor: Neurocrine Biosciences
Sponsor class: INDUSTRY
Collaborators: name: Voyager Therapeutics
First posted: 2018-06-19
Enrollment: 14
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, Sham Surgery Controlled, Double-blind, Multi-center
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with treatment-emergent adverse events (TEAEs)
timeFrame: Up to 5 years after surgery
Secondary outcomes:
Other outcomes:
Locations:
city: Irvine
country: United States
facility: UC Irvine
state: California
city: Sacramento
country: United States
facility: UC Davis Health System
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Chicago
country: United States
facility: Northwestern Medical Faculty Foundation
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: Columbus
country: United States
facility: Ohio State University Clinical Trials Management Office
state: Ohio
city: Philadelphia
country: United States
facility: University of Philadelphia, Dept of Neurology
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center (UPMC)
state: Pennsylvania
Study officials:
affiliation: Neurocrine Biosciences
name: Clinical Development Lead
role: STUDY_DIRECTOR
References:
citation: 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.