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

February 28, 2020 updated by: Neurocrine Biosciences

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

Safety study of AADC gene transfer (VY-AADC01) in subjects with Parkinson's disease.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

15

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94143
        • University of California, San Francisco
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

38 years to 68 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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®).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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 Names:
  • 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 Names:
  • AAV2-hAADC

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
3 Years after Gene Transfer

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
3 Years after Gene Transfer
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.
6 Months after Gene Transfer

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Neurocrine Biosciences

Collaborators

Oregon Health and Science University
University of California, San Francisco
Veristat, Inc.
Feinstein Institute for Medical Research
Voyager Therapeutics

Investigators

  • Study Director: Steve Hersch, MD, Voyager Therapeutics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2013

Primary Completion (Actual)

January 24, 2020

Study Completion (Actual)

January 24, 2020

Study Registration Dates

First Submitted

October 25, 2013

First Submitted That Met QC Criteria

October 25, 2013

First Posted (Estimate)

October 31, 2013

Study Record Updates

Last Update Posted (Actual)

March 3, 2020

Last Update Submitted That Met QC Criteria

February 28, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PD-1101
  • 1302-1209 (Registry Identifier: NIH OBA)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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