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Safety Study of AADC Gene Therapy (VY-AADC01) for Parkinson's Disease (AADC)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
University of California, San Francisco
Veristat, Inc.
Feinstein Institute for Medical Research
Oregon Health and Science University
Information provided by (Responsible Party):
Voyager Therapeutics
ClinicalTrials.gov Identifier:
NCT01973543
First received: October 25, 2013
Last updated: June 26, 2017
Last verified: June 2017
  Purpose
Safety study of AADC gene transfer (VY-AADC01) in subjects with Parkinson's disease.

Condition Intervention Phase
Parkinson's Disease Biological: VY-AADC01 Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:
VY-AADC01
Masking: Outcomes Assessor
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Voyager Therapeutics:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 15
Actual Study Start Date: October 2013
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: VY-AADC01 Dose 1
7.5 x 10^11 vector genomes of VY-AADC01; Single dose, neurosurgically infused, bilaterally into the striatum.
Biological: VY-AADC01
Neurosurgical delivery of VY-AADC01 to the brain.
Other Name: AAV2-hAADC
Experimental: VY-AADC01 Dose 2
1.5 x 10^12 vector genomes of VY-AADC01; Single dose, neurosurgically infused, bilaterally into the striatum.
Biological: VY-AADC01
Neurosurgical delivery of VY-AADC01 to the brain.
Other Name: AAV2-hAADC
Experimental: VY-AADC01 Dose 3
4.7x 10^12 vector genomes of VY-AADC01; Single dose, neurosurgically infused, bilaterally into the striatum.
Biological: VY-AADC01
Neurosurgical delivery of VY-AADC01 to the brain.
Other Name: AAV2-hAADC

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.

  Eligibility

Ages Eligible for Study:   40 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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®).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01973543

Locations
United States, California
University of California, San Francisco
San Francisco, California, United States, 94143
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
Voyager Therapeutics
University of California, San Francisco
Veristat, Inc.
Feinstein Institute for Medical Research
Oregon Health and Science University
Investigators
Study Director: Bernard Ravina, MD, MS Voyager Therapeutics
  More Information

Additional Information:
Responsible Party: Voyager Therapeutics
ClinicalTrials.gov Identifier: NCT01973543     History of Changes
Other Study ID Numbers: PD-1101
1302-1209 ( Registry Identifier: NIH OBA )
Study First Received: October 25, 2013
Last Updated: June 26, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Voyager Therapeutics:
AADC
AAV2-AADC
VY-AADC01
PD
Parkinson's disease
Aromatic Amino Acid Decarboxylase
AAV2
Viral Vector
Gene Therapy
Gene Transfer
MRI
PET

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

ClinicalTrials.gov processed this record on July 19, 2017