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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 : November 13, 2019
Sponsor:
Collaborator:
Voyager Therapeutics
Information provided by (Responsible Party):
Neurocrine Biosciences

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

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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
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Contact: Restore-1 Call Center 855-465-8607 info@restore1pdstudy.com

Locations
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United States, California
UC Irvine Recruiting
Irvine, California, United States, 92697
Contact: Breana Chew    949-824-7524    chewbc@hs.uci.edu   
Principal Investigator: Neal Hermanowicz, MD         
UC Davis Health System Recruiting
Sacramento, California, United States, 95817
Contact: Olga Kishchenko, CCRP    916-703-9173    okishchenko@ucdavis.edu   
Principal Investigator: Lin Zhang, MD,PhD         
San Francisco VA Medical Center Recruiting
San Francisco, California, United States, 94143
Contact: Marin Thompson, MS, CCRP    415-353-9666    aadc@ucsf.edu   
Principal Investigator: Paul Larson, MD         
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Marin Thompson, MS, CCRP    415-353-9666    aadc@ucsf.edu   
Principal Investigator: Chad Christine, MD         
United States, Colorado
University of Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Abby Simpson    303-724-3974    abigail.simpson@cuanschutz.edu   
Contact: Marissa Garcia    303-724-2197    marissa.garcia@cuanschutz.edu   
Principal Investigator: Steven Ojemann, MD         
United States, Georgia
Emory University Hospital Recruiting
Atlanta, Georgia, United States, 30322
Contact: Carole Seeley, RN    404-727-8748    carole.seeley@emory.edu   
Principal Investigator: Steward Factor, DO         
United States, Illinois
Northwestern Medical Faculty Foundation Recruiting
Chicago, Illinois, United States, 60611
Contact: Justine Houseman    312-503-2128    justine.houseman@northwestern.edu   
Principal Investigator: Avram Fraint, MD         
United States, Kansas
University of Kansas Medical Center Recruiting
Kansas City, Kansas, United States, 66160
Contact: April Langhammer    913-588-6989    alanghammer@kumc.edu   
Principal Investigator: Rajesh Pahwa, MD         
United States, Massachusetts
Tufts Medical Center Recruiting
Boston, Massachusetts, United States, 02111
Contact: Keri Sullivan    617-636-7620    ksullivan22@tuftsmedicalcenter.org   
Principal Investigator: Bryan Ho, MD         
Beth Israel Deaconess Medical Center (BIDMC) Recruiting
Boston, Massachusetts, United States, 02215
Contact: Stephanie Burrows    617-667-9885    sburrows@bidmc.harvard.edu   
Principal Investigator: David Simon         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Angela Stovall    734-647-4787    astovall@med.umich.edu   
Principal Investigator: Kelvin Chou, MD         
Michigan State University Department of Neurology Recruiting
East Lansing, Michigan, United States, 48824
Contact: Doozie Russell    517-884-2274    sniderm@msu.edu   
Principal Investigator: John Goudreau, DO, PhD         
United States, New Jersey
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Harveen Kaur    551-996-1224    Harveen.Kaur@hackensackmeridian.org   
Principal Investigator: Naomi Lubarr         
United States, New York
NYU Langone Medical Center Recruiting
New York, New York, United States, 10017
Contact: Brooklyn Henderson, RN         
Contact    646-501-4367    Brooklyn.Henderson@nyulangone.org   
Principal Investigator: Andrew Feigin, MD         
United States, Ohio
Cleveland Clinic-Center for Neurological Restoration Recruiting
Cleveland, Ohio, United States, 44195
Contact: Michael Zeleny    216-445-1861    zelenym@ccf.org   
Principal Investigator: Michal Gostkowski, DO         
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   
Principal Investigator: Sandra K. Kostyk, MD,PhD         
United States, Pennsylvania
The Hospital of the University of Pennsylvania Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Principal Investigator: Gordon Baltuch, MD,PhD         
Thomas Jefferson University Hospital Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Karishma Kurowski    215-503-3166    Karishma.Kurowski@jefferson.edu   
Principal Investigator: Daniel Kremens, MD         
University of Philadelphia, Dept of Neurology Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Ellen Rosen    212-829-5254    ellen.rosen@uphs.upenn.edu   
Principal Investigator: Andrew Siderowf, MD         
University of Pittsburgh Medical Center (UPMC) Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Deena Ratner    412-692-4302    ratnerdm2@upmc.edu   
Principal Investigator: Amber Van Laar, MD         
Sponsors and Collaborators
Neurocrine Biosciences
Voyager Therapeutics
Investigators
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Study Director: Steve Hersch, MD Voyager Therapeutics

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Neurocrine Biosciences
ClinicalTrials.gov Identifier: NCT03562494     History of Changes
Other Study ID Numbers: PD-1105
First Posted: June 19, 2018    Key Record Dates
Last Update Posted: November 13, 2019
Last Verified: November 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Neurocrine Biosciences:
PD, Parkinson's disease
Aromatic L-Amino Acid Decarboxylase
AADC
AAV2-AADC
AAV2
VY-AADC
AAV2-hAADC
Additional relevant MeSH terms:
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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