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Trial record 1 of 3 for:    Voyager, AADC gene
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Safety Study of AADC Gene Therapy (VY-AADC01) for Parkinson's Disease (AADC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01973543
Recruitment Status : Completed
First Posted : October 31, 2013
Last Update Posted : March 3, 2020
Sponsor:
Collaborators:
University of California, San Francisco
Veristat, Inc.
Feinstein Institute for Medical Research
Oregon Health and Science University
Voyager Therapeutics
Information provided by (Responsible Party):
Neurocrine Biosciences

Tracking Information
First Submitted Date  ICMJE October 25, 2013
First Posted Date  ICMJE October 31, 2013
Last Update Posted Date March 3, 2020
Actual Study Start Date  ICMJE October 2013
Actual Primary Completion Date January 24, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 25, 2013)
Safety of AADC Gene Transfer [ Time Frame: 3 Years after Gene Transfer ]
Safety and Tolerability of AADC Gene Transfer assessed by Adverse Events and Serious Adverse Events.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 16, 2016)
  • Parkinson's Symptoms [ Time Frame: 3 Years after Gene Transfer ]
    Effect of AAV2-hAADC on Parkinson's symptoms as recorded in subject diaries, neurological, motor, and non-motor assessments, quality of life surveys and changes to Parkinson's medications.
  • PET Scan Imaging [ Time Frame: 6 Months after Gene Transfer ]
    Relationship between AAV2 distribution in the brain and change in AADC expression as seen in PET imaging.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 25, 2013)
  • Parkinson's Symptoms [ Time Frame: 3 Years after Gene Transfer ]
    Effect of AAV2-hAADC on Parkinson's symptoms as recorded in subject diaries, neurological and motor assessments, quality of life surveys and changes to Parkinson's medications.
  • PET Scan Imaging [ Time Frame: 6 Months after Gene Transfer ]
    Relationship between AAV2 distribution in the brain and change in AADC expression as seen in PET imaging.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety Study of AADC Gene Therapy (VY-AADC01) for Parkinson's Disease
Official Title  ICMJE An Open-label Safety and Efficacy Study of VY-AADC01 Administered by MRI-Guided Convective Infusion Into the Putamen of Subjects With Parkinson's Disease With Fluctuating Responses to Levodopa
Brief Summary Safety study of AADC gene transfer (VY-AADC01) in subjects with Parkinson's disease.
Detailed Description

Parkinson's disease is a neurodegenerative disorder involving loss of neurons that release dopamine in the striatum. To compensate for the loss of dopamine, patients are typically prescribed levodopa medication which is converted to dopamine by the enzyme Aromatic L-Amino Acid Decarboxylase (AADC). As Parkinson's disease progresses, levodopa therapy becomes less effective and is associated with motor fluctuations, involuntary movements and other complications.

This study will primarily investigate the safety of increasing AADC levels in the striatum via AADC gene delivery. The hAADC gene is packaged into a gene transfer vector derived from a common, non-pathogenic virus (AAV2) to which >90% of humans have been exposed. This investigational drug, termed VY-AADC01, will be injected directly into the striatum during a neurosurgical procedure that is performed with real-time MRI imaging to monitor delivery.

Subjects will continue to take Parkinson's disease medications, including levodopa.

The safety and potential clinical responses to VY-AADC01 will be assessed by repeated clinical evaluations of Parkinson's disease, cognitive tests, laboratory blood tests and neuroimaging. Clinical evaluations will be performed over a 3 year follow-up period. A test to specifically assess the clinical response to levodopa will be performed once before AADC gene delivery and approximately 6 months after.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:
VY-AADC01
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Parkinson's Disease
Intervention  ICMJE Biological: VY-AADC01
Neurosurgical delivery of VY-AADC01 to the brain.
Other Name: AAV2-hAADC
Study Arms  ICMJE
  • Experimental: VY-AADC01 Dose 1
    7.5 x 10^11 vector genomes of VY-AADC01; Single dose, neurosurgically infused, bilaterally into the striatum.
    Intervention: Biological: VY-AADC01
  • Experimental: VY-AADC01 Dose 2
    1.5 x 10^12 vector genomes of VY-AADC01; Single dose, neurosurgically infused, bilaterally into the striatum.
    Intervention: Biological: VY-AADC01
  • Experimental: VY-AADC01 Dose 3
    4.7x 10^12 vector genomes of VY-AADC01; Single dose, neurosurgically infused, bilaterally into the striatum.
    Intervention: Biological: VY-AADC01
Publications * Christine CW, Bankiewicz KS, Van Laar AD, Richardson RM, Ravina B, Kells AP, Boot B, Martin AJ, Nutt J, Thompson ME, Larson PS. Magnetic resonance imaging-guided phase 1 trial of putaminal AADC gene therapy for Parkinson's disease. Ann Neurol. 2019 May;85(5):704-714. doi: 10.1002/ana.25450. Epub 2019 Mar 26.

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: June 26, 2017)
15
Original Estimated Enrollment  ICMJE
 (submitted: October 25, 2013)
10
Actual Study Completion Date  ICMJE January 24, 2020
Actual Primary Completion Date January 24, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosed with idiopathic Parkinson's disease
  • Disease duration of at least 5 years or more
  • Adequate duration of levodopa therapy
  • Modified Hoehn and Yahr Staging of at least 2.5 in the OFF state
  • Candidate for surgical intervention because of disabling motor complications.
  • UPDRS Part III (total motor) score ≥ 25 and a maximum of 60 in the OFF state.
  • Unequivocal responsiveness to dopaminergic therapy.
  • Stable Parkinson's symptoms and medication regimen for at least 4 weeks prior to screening examination.
  • Ability to comprehend and sign the informed consent.
  • Normal Laboratory values prior to surgery.
  • Neutralizing AAV2 antibody titer ≤ 1:1200
  • Ability to travel to study visits alone or able to designate a caregiver.
  • Subject agrees to defer any neurological surgery, including deep brain stimulation, until after completing the 12 month study visit (unless recommended by study neurologist).
  • Subject agrees to not participate in any other therapeutic intervention study for 12 months after surgery.
  • Subject agrees to not have any vaccinations within 30 days of surgery.

Exclusion Criteria:

  • 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.
  • Presence of dementia as defined by a Mattis Dementia Rating Scale-Second Edition (MDRS-2) of less than 130 at screening.
  • Presence or history of psychosis, with the exception of mild, benign hallucinations believed in the judgment of the investigators to be related to Parkinson's medications.
  • Presence of severe depression as measured by Beck Depression Inventory II (BDI-II) > 28 or a history of a major affective disorder within 5 years of screening examination.
  • Current suicidal ideation or suicide attempt within 5 years of screening examination.
  • History of substance abuse within 2 years of screening examination.
  • Brain imaging abnormalities in the striatum or other regions that would substantially increase risk of surgery.
  • Contraindication to MRI and/or gadoteridol.
  • Coagulopathy or inability to temporarily stop any anticoagulation or antiplatelet prior to surgery.
  • Prior brain surgery including deep brain stimulation, infusion therapies or any other brain surgery.
  • Prior gene transfer.
  • History of stroke, poorly controlled or significant cardiovascular disease, diabetes or any other acute or chronic medical condition.
  • History of malignancy other than treated carcinoma in situ within three years of screening evaluation.
  • Clinically apparent or laboratory-detected infection.
  • Prior or current treatment with any investigational agent within 2 months of screening evaluation.
  • Chronic immunosuppressive therapy, including chronic steroids, immunotherapy, cytotoxic therapy and chemotherapy.
  • Pregnant and lactating women.
  • Subject with reproductive capacity who is unwilling to use barrier contraception.
  • Any medical condition that is likely to lead to disability during the course of the study and interfere with confound study assessments
  • Any factors, medical, or social, which would likely cause the subject to be unable to follow the study protocol, including geographical inaccessibility.
  • Ongoing treatments such as, neuroleptic medications, apomorphine, or levodopa infusion therapy (Duodopa®).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years to 70 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 NCT01973543
Other Study ID Numbers  ICMJE PD-1101
1302-1209 ( Registry Identifier: NIH OBA )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Neurocrine Biosciences
Study Sponsor  ICMJE Neurocrine Biosciences
Collaborators  ICMJE
  • University of California, San Francisco
  • Veristat, Inc.
  • Feinstein Institute for Medical Research
  • Oregon Health and Science University
  • Voyager Therapeutics
Investigators  ICMJE
Study Director: Steve Hersch, MD Voyager Therapeutics
PRS Account Neurocrine Biosciences
Verification Date February 2020

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