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Trial record 1 of 1 for:    NCT03562494
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VY-AADC02 for Parkinson's Disease With Motor Fluctuations (RESTORE-1)

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ClinicalTrials.gov Identifier: NCT03562494
Recruitment Status : Active, not recruiting
First Posted : June 19, 2018
Last Update Posted : January 20, 2021
Sponsor:
Collaborator:
Voyager Therapeutics
Information provided by (Responsible Party):
Neurocrine Biosciences

Tracking Information
First Submitted Date  ICMJE May 16, 2018
First Posted Date  ICMJE June 19, 2018
Last Update Posted Date January 20, 2021
Actual Study Start Date  ICMJE June 28, 2018
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 26, 2020)
Change in ON time without troublesome dyskinesia as recorded by participant in Parkinson's Disease (PD) diary [ Time Frame: Baseline to Day 360 ]
Original Primary Outcome Measures  ICMJE
 (submitted: June 7, 2018)
  • Change in Patient Rated Motor Fluctuations in the VY-AADC02 group compared to placebo surgery group. [ Time Frame: Baseline to 12 months post op ]
    Patient recorded Parkinson's Disease (PD) diary.
  • Percent coverage within the putamen at time of administration of VY-AADC02. [ Time Frame: Day of Surgery ]
    Measured by intra-operative magnetic resonance imaging (MRI).
  • Change in AADC enzyme activity (Distribution). [ Time Frame: 45 days and 12 months post op ]
    Percent change from baseline in Aromatic L-Amino Acid Decarboxylase (AADC) expression as measured by [18F]-fluorodopa (F-Dopa) positron emission tomography (PET).
  • Safety of VY-AADC02 as measured by number of treatment emergent adverse events (TEAEs) and Serious Adverse Events (SAEs). [ Time Frame: Informed Consent to 12 months post op + 30 day Follow Up ]
    TEAS and SAEs will be assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03.
  • Safety of VY-AADC02 as measured by changes in vital signs. [ Time Frame: Informed Consent to 12 months post op + 30 day Follow Up ]
    Number of clinically significant changes in vital signs.
  • Safety of VY-AADC02 as measured by physical examinations and routine clinical laboratory analysis (hematology and clinical chemistry). [ Time Frame: Informed Consent to 12 months post op + 30 day Follow Up ]
    Number of clinically significant changes in physical examinations and routine clinical laboratory analysis (hematology and clinical chemistry).
  • Safety of VY-AADC02 as measured by changes in findings on brain images. [ Time Frame: Informed Consent to 12 months post op + 30 day Follow Up ]
    Measured by number of clinically significant changes in intra-operative and follow-up findings on brain images.
  • Safety of VY-AADC02 as measured by the Columbia-Suicide Severity Rating Scale (C-SSRS). [ Time Frame: Informed Consent to 12 months post op + 30 day Follow Up ]
    Measure by the Columbia-Suicide Severity Rating Scale (C-SSRS).
  • Safety of VY-AADC02 based on change in impulse control disorders. [ Time Frame: Informed Consent to 12 months post op + 30 day Follow Up ]
    Measured by the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP RS).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 26, 2020)
  • Change in Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III score in the OFF state [ Time Frame: Baseline to Day 360 ]
  • Change in MDS-UPDRS II score [ Time Frame: Baseline to Day 360 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 7, 2018)
  • Change in activities of daily living in the VY-AADC02 group compared to placebo surgery group. [ Time Frame: Baseline to 12 months post-op ]
    Measured by Unified Parkinson's Disease Rating Scale (UPDRS) II score.
  • Change in PD related quality of life in the VY-AADC02 group compared to placebo surgery group. [ Time Frame: Baseline to 12 months post-op ]
    Measured by the Parkinson's Disease Questionnaire (PDQ-39) summary index.
  • Change from baseline in time course response to levodopa in the VY-AADC02 group. compared to placebo surgery group measured by the area under the curve (AUC) of repeated UPDRS III scores following a single dose of oral levodopa [ Time Frame: Baseline to 12 months post-op ]
    Measured by Unified Parkinson's Disease Rating Scale (UPDRS) II score.
  • Change in global function in the VY-AADC02 group compared to placebo surgery group. [ Time Frame: Baseline to 12 months post-op ]
    Measured by the proportion of participants with improvement on the Clinical Global Impression (CGI) of change score.
  • Change in overall non-motor symptoms in the VY-AADC02 group compared to placebo surgery group. [ Time Frame: Baseline to 12 months post-op ]
    Measured by the Non-Motor Symptom Scale (NMSS).
Current Other Pre-specified Outcome Measures
 (submitted: June 26, 2020)
Safety outcome measured by treatment emergent adverse events (TEAEs), serious adverse events (SAEs), changes in vital signs and clinical laboratory analysis, and immunogenicity [ Time Frame: Baseline to Day 360 ]
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE VY-AADC02 for Parkinson's Disease With Motor Fluctuations (RESTORE-1)
Official Title  ICMJE A Randomized, Sham Surgery Controlled, Double-blind, Multi-center, Phase 2 Clinical Trial, Evaluating the Efficacy and Safety of VY-AADC02 in Moderate to Advanced Parkinson's Disease Patients With Motor Fluctuations
Brief Summary The objectives of this study are to assess the efficacy, safety and tolerability of VY-AADC02 in Patients with Parkinson's Disease with Motor Fluctuations.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Randomized, Sham Surgery Controlled, Double-blind, Multi-center
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Parkinson's Disease
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Experimental: VY-AADC02 (NBIb-1817)
    Single administration of up to 3.6 x 10^12 vector genomes (vg) of VY-AADC02
    Intervention: Biological: VY-AADC02
  • Placebo Comparator: Sham (Placebo) Surgery
    Sham surgical procedure
    Intervention: Other: Sham (Placebo) Surgery
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: June 26, 2020)
85
Original Estimated Enrollment  ICMJE
 (submitted: June 7, 2018)
42
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 MDS-UPDRS III score
  4. Disease duration from diagnosis of ≥4 years
  5. An average of ≥3 hours of OFF time (ie, 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. 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 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03562494
Other Study ID Numbers  ICMJE PD-1105
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Neurocrine Biosciences
Study Sponsor  ICMJE Neurocrine Biosciences
Collaborators  ICMJE Voyager Therapeutics
Investigators  ICMJE
Study Director: Grace Liang, MD Neurocrocrine Biosciences
PRS Account Neurocrine Biosciences
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP