Recruitment

Recruitment Status
Completed
Estimated Enrollment
10

Inclusion Criterias

Ability to travel to study visits alone or able to designate a caregiver.
Disease duration of at least 5 years or more
Neutralizing AAV2 antibody titer ≤ 1:1200
...
Ability to travel to study visits alone or able to designate a caregiver.
Disease duration of at least 5 years or more
Neutralizing AAV2 antibody titer ≤ 1:1200
Candidate for surgical intervention because of disabling motor complications.
Subject agrees to not have any vaccinations within 30 days of surgery.
Normal Laboratory values prior to surgery.
Stable Parkinson's symptoms and medication regimen for at least 4 weeks prior to screening examination.
Ability to comprehend and sign the informed consent.
Unequivocal responsiveness to dopaminergic therapy.
Subject agrees to not participate in any other therapeutic intervention study for 12 months after surgery.
Modified Hoehn and Yahr Staging of at least 2.5 in the OFF state
UPDRS Part III (total motor) score ≥ 25 and a maximum of 60 in the OFF state.
Subject agrees to defer any neurological surgery, including deep brain stimulation, until after completing the 12 month study visit (unless recommended by study neurologist).
Diagnosed with idiopathic Parkinson's disease
Adequate duration of levodopa therapy

Exclusion Criterias

Clinically apparent or laboratory-detected infection.
History of malignancy other than treated carcinoma in situ within three years of screening evaluation.
Pregnant and lactating women.
...
Clinically apparent or laboratory-detected infection.
History of malignancy other than treated carcinoma in situ within three years of screening evaluation.
Pregnant and lactating women.
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.
Contraindication to MRI and/or gadoteridol.
History of stroke, poorly controlled or significant cardiovascular disease, diabetes or any other acute or chronic medical condition.
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.
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.
Chronic immunosuppressive therapy, including chronic steroids, immunotherapy, cytotoxic therapy and chemotherapy.
History of substance abuse within 2 years of screening examination.
Prior brain surgery including deep brain stimulation, infusion therapies or any other brain surgery.
Coagulopathy or inability to temporarily stop any anticoagulation or antiplatelet prior to surgery.
Prior gene transfer.
Any medical condition that is likely to lead to disability during the course of the study and interfere with confound study assessments
Brain imaging abnormalities in the striatum or other regions that would substantially increase risk of surgery.
Presence of dementia as defined by a Mattis Dementia Rating Scale-Second Edition (MDRS-2) of less than 130 at screening.
Prior or current treatment with any investigational agent within 2 months of screening evaluation.
Subject with reproductive capacity who is unwilling to use barrier contraception.
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®).
Current suicidal ideation or suicide attempt within 5 years of screening examination.

Summary

Conditions
Parkinson's Disease
Type
Interventional
Phase
Phase 1
Design
  • Allocation: Non-Randomized
  • Intervention Model: Single Group Assignment
  • Intervention Model Description: VY-AADC01Masking: Single (Outcomes Assessor)
  • Primary Purpose: Treatment

Participation Requirements

Age
Between 40 years and 70 years
Gender
Both males and females

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). ...

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.

Inclusion Criterias

Ability to travel to study visits alone or able to designate a caregiver.
Disease duration of at least 5 years or more
Neutralizing AAV2 antibody titer ≤ 1:1200
...
Ability to travel to study visits alone or able to designate a caregiver.
Disease duration of at least 5 years or more
Neutralizing AAV2 antibody titer ≤ 1:1200
Candidate for surgical intervention because of disabling motor complications.
Subject agrees to not have any vaccinations within 30 days of surgery.
Normal Laboratory values prior to surgery.
Stable Parkinson's symptoms and medication regimen for at least 4 weeks prior to screening examination.
Ability to comprehend and sign the informed consent.
Unequivocal responsiveness to dopaminergic therapy.
Subject agrees to not participate in any other therapeutic intervention study for 12 months after surgery.
Modified Hoehn and Yahr Staging of at least 2.5 in the OFF state
UPDRS Part III (total motor) score ≥ 25 and a maximum of 60 in the OFF state.
Subject agrees to defer any neurological surgery, including deep brain stimulation, until after completing the 12 month study visit (unless recommended by study neurologist).
Diagnosed with idiopathic Parkinson's disease
Adequate duration of levodopa therapy

Exclusion Criterias

Clinically apparent or laboratory-detected infection.
History of malignancy other than treated carcinoma in situ within three years of screening evaluation.
Pregnant and lactating women.
...
Clinically apparent or laboratory-detected infection.
History of malignancy other than treated carcinoma in situ within three years of screening evaluation.
Pregnant and lactating women.
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.
Contraindication to MRI and/or gadoteridol.
History of stroke, poorly controlled or significant cardiovascular disease, diabetes or any other acute or chronic medical condition.
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.
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.
Chronic immunosuppressive therapy, including chronic steroids, immunotherapy, cytotoxic therapy and chemotherapy.
History of substance abuse within 2 years of screening examination.
Prior brain surgery including deep brain stimulation, infusion therapies or any other brain surgery.
Coagulopathy or inability to temporarily stop any anticoagulation or antiplatelet prior to surgery.
Prior gene transfer.
Any medical condition that is likely to lead to disability during the course of the study and interfere with confound study assessments
Brain imaging abnormalities in the striatum or other regions that would substantially increase risk of surgery.
Presence of dementia as defined by a Mattis Dementia Rating Scale-Second Edition (MDRS-2) of less than 130 at screening.
Prior or current treatment with any investigational agent within 2 months of screening evaluation.
Subject with reproductive capacity who is unwilling to use barrier contraception.
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®).
Current suicidal ideation or suicide attempt within 5 years of screening examination.

Locations

San Francisco, California, 94143
Pittsburgh, Pennsylvania, 15213
San Francisco, California, 94143
Pittsburgh, Pennsylvania, 15213

Tracking Information

NCT #
NCT01973543
Collaborators
  • University of California, San Francisco
  • Veristat, Inc.
  • Feinstein Institute for Medical Research
  • Oregon Health and Science University
  • Voyager Therapeutics
Investigators
Study Director: Steve Hersch, MD Voyager Therapeutics