Safety and Efficacy Study of VY-AADC01 for Advanced Parkinson's Disease

This is an interventional treatment trial for Idiopathic Parkinson's Disease focused on measuring Gene Therapy, PD, Parkinson's Disease, Aromatic L- Amino Acid Decarboxylase, AADC, AAV2-AADC, AAV2, Viral Vector, Gene Transfer, MRI, PET, VY-AADC01 Read More

Inclusion Criteria:

• Diagnosed with idiopathic PD.
• Adequate duration of levodopa therapy.
• Disease duration of at least 5 years or more.
• Modified Hoehn & Yahr Staging with at least 2.5 hours or more in the OFF state.
• Candidate for surgical intervention because of disabling motor complications.
• UPDRS Part III (total score) of at least 25 in the OFF state.
• Unequivocal responsiveness to dopaminergic therapy.
• Stable Parkinson's symptoms and medications for at least 4 weeks prior to screening evaluation.
• Ability to comprehend and sign the informed consent.
• Normal laboratory values prior to surgery.
• Medically and mentally capable of undergoing and complying with the surgical procedure and protocol requirements.
• 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).
• Approved by the Eligibility Review Committee.

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) score of less than 130 at screening.
• Presence or history of psychosis, with the exception of mild, benign hallucinations believed in the judgment of the Investigator to be related to Parkinson's medications.
• Presence of severe depression, as indicated by a BDI-II score greater than 28, or a history of a major affective disorder within 5 years of screening evaluation.
• Active suicidal ideation or suicide attempt within 5 years of screening evaluation.
• History of substance abuse within 2 years of screening evaluation.
• 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 therapy prior to surgery.
• Prior brain surgery including lesioning procedures, 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 3 years of screening evaluation.
• Clinically apparent or laboratory-detected infection.
• Prior or current treatment with any investigational agent within 2 months of screening evaluation.
• Inability to comply with the procedures of the protocol, including completion of paper Parkinson's disease diaries, frequent and prolonged study visits including off medication visits, and travel.
• Chronic immunosuppressive therapy, including chronic steroids, immunotherapy, cytotoxic therapy, and chemotherapy.
• Any serious medical condition or abnormal finding on physical examination or laboratory investigation that would substantially increase the risks of the study procedures.
• Any medical condition that is likely to lead to disability during the course of the study and interfere with or confound study assessments.
• Pregnant and lactating women.
• Male or female with reproductive capacity who is unwilling to use barrier contraception for 6 months after surgery.
• Plans to receive any vaccination within 30 days of surgery.
• Any factors, medical or social, which would likely cause the participant to be unable to follow the study protocol, including geographical inaccessibility.
• Ongoing treatments including neuroleptic medications, apomorphine, or levodopa infusion therapy (Duopa®).
• Plans to participate in any other therapeutic intervention study within 12 months after surgery.