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

• Status: Active, not recruiting
• Trial end date: 2021-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Safety and efficacy of AADC gene transfer in participants with Parkinson's disease.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Neurocrine Biosciences; Voyager Therapeutics
• Collaborator: Voyager Therapeutics

Criteria

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.