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VY-AADC02 for Parkinson's Disease With Motor Fluctuations

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ClinicalTrials.gov Identifier: NCT03562494
Recruitment Status : Recruiting
First Posted : June 19, 2018
Last Update Posted : December 11, 2018
Sponsor:
Information provided by (Responsible Party):
Voyager Therapeutics

Brief Summary:
The objectives of this study are to assess the distribution, efficacy, and safety of VY-AADC02 in Patients with Parkinson's Disease with Motor Fluctuations.

Condition or disease Intervention/treatment Phase
Parkinson Disease Biological: VY-AADC02 Other: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, Placebo Surgery Controlled, Double-blinded, Multi-center
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Placebo Surgery Controlled, Double-blinded, Multi-center, Phase 2 Clinical Trial, Evaluating the Efficacy and Safety of VY-AADC02 in Advanced Parkinson's Disease With Motor Fluctuations
Actual Study Start Date : June 28, 2018
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: VY-AADC02
Single dose of up to 2.5 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). VY-AADC02 is infused by a neurosurgeon into the brain.

Placebo Comparator: Placebo (Sham)
Partial burr/twist hole without dura penetration
Other: Placebo
Placebo (sham) Surgery




Primary Outcome Measures :
  1. 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.

  2. 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).

  3. 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).

  4. 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.

  5. 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.

  6. 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).

  7. 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.

  8. 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).

  9. 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).


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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).



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Ages Eligible for Study:   40 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. Unequivocal responsiveness to dopaminergic therapy, as judged by the Investigator.
  4. Disease duration from diagnosis of ≥4 years.
  5. In the judgment of the Investigator, a stable, optimal regimen of Parkinson's medications for at least 4 weeks prior to screening evaluation.
  6. Stable cognitive and psychological function based on screening evaluations.
  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 neurological surgery, including deep brain stimulation, other invasive treatments for PD including duodopa, or the addition of new dopaminergic formulations until after completing the 12-month study visit.
  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. Use of tetrahydrocannabinol within 6 months of screening evaluation.
  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 or infusion therapies 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. Ongoing treatments or planned treatments that might interfere with interpretation of the study outcome including deep brain stimulation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03562494


Contacts
Contact: Kenneth J Adams, B.S. (857) 856-4148 clinicaltrials@vygr.com
Contact: Stephanie D'Eon 857-856-4177 clinicaltrials@vygr.com

Locations
United States, California
UC Irvine Recruiting
Irvine, California, United States, 92697
Contact: Jaclyn Alcazar    949-824-1114    jaclyn.alcazar@uci.edu   
Principal Investigator: Neal Hermanowicz, MD         
San Francisco Veterans Affairs Medical Center Recruiting
San Francisco, California, United States, 94143
Contact: Marin Thompson    415-353-9666    aadc@ucsf.edu   
Principal Investigator: Paul Larsen, MD         
United States, Georgia
Emory University Hospital Recruiting
Atlanta, Georgia, United States, 30322
Contact: Carole Seeley, RN    404-712-7013    carole.seeley@emory.edu   
United States, Michigan
Michigan State University Department of Neurology Recruiting
East Lansing, Michigan, United States, 48824
Contact: Doozie Russell    517-884-2274    Doozie.russell@hc.msu.edu   
Principal Investigator: John Goudreau, DO, PhD         
United States, New York
NYU Langone Medical Center Recruiting
New York, New York, United States, 10017
Contact: Brooklyn Henderson, RN         
Contact    646-501-4367      
Principal Investigator: Andrew Feigin, MD         
United States, Ohio
Ohio State University Clinical Trials Management Office Recruiting
Columbus, Ohio, United States, 43210
Contact: Katherine Ambrogi, BSN, RN    614-688-6685    katherine.ambrogi@osumc.edu   
United States, Pennsylvania
University of Pittsburgh Medical Center (UPMC) Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: R. Mark Richardson, MD, PhD         
Sponsors and Collaborators
Voyager Therapeutics
Investigators
Study Director: Steve Hersch, MD Voyager Therapeutics

Responsible Party: Voyager Therapeutics
ClinicalTrials.gov Identifier: NCT03562494     History of Changes
Other Study ID Numbers: PD-1105
First Posted: June 19, 2018    Key Record Dates
Last Update Posted: December 11, 2018
Last Verified: December 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Voyager Therapeutics:
PD, Parkinson's disease
Aromatic L-Amino Acid Decarboxylase
AADC
AAV2-AADC
AAV2
VY-AADC
AAV2-hAADC

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Dopa Decarboxylase
Antiparkinson Agents
Anti-Dyskinesia Agents