Safety Study of AADC Gene Therapy (VY-AADC01) for Parkinson's Disease
AADC
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
2 other identifiers
interventional
15
1 country
2
Brief Summary
Safety study of AADC gene transfer (VY-AADC01) in subjects with Parkinson's disease.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Oct 2013
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
October 1, 2013
CompletedFirst Submitted
Initial submission to the registry
October 25, 2013
CompletedFirst Posted
Study publicly available on registry
October 31, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 24, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
January 24, 2020
CompletedMarch 3, 2020
February 1, 2020
6.3 years
October 25, 2013
February 28, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Safety of AADC Gene Transfer
Safety and Tolerability of AADC Gene Transfer assessed by Adverse Events and Serious Adverse Events.
3 Years after Gene Transfer
Secondary Outcomes (2)
Parkinson's Symptoms
3 Years after Gene Transfer
PET Scan Imaging
6 Months after Gene Transfer
Study Arms (3)
VY-AADC01 Dose 1
EXPERIMENTAL7.5 x 10\^11 vector genomes of VY-AADC01; Single dose, neurosurgically infused, bilaterally into the striatum.
VY-AADC01 Dose 2
EXPERIMENTAL1.5 x 10\^12 vector genomes of VY-AADC01; Single dose, neurosurgically infused, bilaterally into the striatum.
VY-AADC01 Dose 3
EXPERIMENTAL4.7x 10\^12 vector genomes of VY-AADC01; Single dose, neurosurgically infused, bilaterally into the striatum.
Interventions
Neurosurgical delivery of VY-AADC01 to the brain.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Neurocrine Bioscienceslead
- University of California, San Franciscocollaborator
- Veristat, Inc.collaborator
- Feinstein Institute for Medical Researchcollaborator
- Oregon Health and Science Universitycollaborator
- Voyager Therapeuticscollaborator
Study Sites (2)
University of California, San Francisco
San Francisco, California, 94143, United States
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213, United States
Related Publications (2)
Christine CW, Richardson RM, Van Laar AD, Thompson ME, Fine EM, Khwaja OS, Li C, Liang GS, Meier A, Roberts EW, Pfau ML, Rodman JR, Bankiewicz KS, Larson PS. Safety of AADC Gene Therapy for Moderately Advanced Parkinson Disease: Three-Year Outcomes From the PD-1101 Trial. Neurology. 2022 Jan 4;98(1):e40-e50. doi: 10.1212/WNL.0000000000012952. Epub 2021 Oct 14.
PMID: 34649873DERIVEDChristine 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.
PMID: 30802998DERIVED
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Steve Hersch, MD
Voyager Therapeutics
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 25, 2013
First Posted
October 31, 2013
Study Start
October 1, 2013
Primary Completion
January 24, 2020
Study Completion
January 24, 2020
Last Updated
March 3, 2020
Record last verified: 2020-02