AADC Gene Therapy for Parkinson's Disease

NCT02418598 | Terminated Phase 1 DMC

• 1 other identifier: JMU-AAV-AADC-PD
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety, efficacy of intra-putaminal infusion of AAV-hAADC-2 (adeno-associated virus encoding human aromatic L-amino acid decarboxylase) by stereotaxic surgery in patients with advanced Parkinson's disease.

Conditions

Parkinson Disease

Keywords

Adeno-associated virus; Aromatic L-amino acid decarboxylase; AAV-hAADC-2; AAV-2; Gene Therapy; Gene Transfer; Parkinson Disease; Basal Ganglia Disease; Brain Disease

Outcome Measures

Primary Outcomes (1)

• The safety of intra-putaminal infusion of AAV-hAADC-2 as measured by adverse events (including Abnormal laboratory test results) with Classification criteria for severity of adverse reactions (dated 29th Jun,1992).

  Confirm the adverse events (including Abnormal laboratory test results) with Classification criteria for severity of adverse reactions (dated 29th Jun,1992).

  6 months

Secondary Outcomes (2)

• The treatment effect of intra-putaminal infusion of AAV-hAADC-2

  6 months

• The amount of intra-putaminal expression of AAV-hAADC-2

  6 months

Study Arms (2)

Cohort1

EXPERIMENTAL

The target putamen for AAV-hAADC-2 infusion is identified on MRI image that has been taken prior to the operation, and then subjects will be bilaterally infused with a total volume of 200 µL at a total of 4 sites (2 sites in left putamen, 2 sites in right putamen; 50 µL per site) at a flow rate of 3 µL per minute.

Genetic: Cohort1

Cohort2

EXPERIMENTAL

The target putamen for AAV-hAADC-2 infusion is identified on MRI image that has been taken prior to the operation, and then subjects will be bilaterally infused with a total volume of 600 µL at a total of 4 sites (2 sites in left putamen, 2 sites in right putamen; 150 µL per site) at a flow rate of 3 µL per minute.

Genetic: Cohort2

Interventions

Cohort1 GENETIC

AAV-hAADC-2 is administered via bilateral intra-putaminal infusion. The number of vector genomes (vg) administered in this cohort is 3x10\^11 vg/subject.

Cohort1

Cohort2 GENETIC

AAV-hAADC-2 is administered via bilateral intra-putaminal infusion. The number of vector genomes (vg) administered in this cohort is 9x10\^11 vg/subject.

Cohort2

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with idiopathic Parkinson's disease meet diagnostic criteria for Specified Disease designated by the Ministry of Health, Labour and Welfare (1995) : the Research Committee of CNS Degenerative Disease, L-Dopa is effective in the early disease stage and no findings suggestive of CNS Degenerative Disease are found.
• Age ≤ 75 years at the time of medical treatment.
• Age at onset ≥ 35 years.
• Duration of L-dopa therapy ≥ 5 years.
• Hoehn and Yahr Stage IV in OFF state at the onset of medical treatment.
• Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Scale Part III (MDS-UPDRS-III), minimum motor score of 30 to a maximum motor score of 100 in OFF state.
• Positive response to dopaminergic therapy as evidenced by remarkable improvement in MDS-UPDRS-III motor score between the defined "OFF" and "ON" state: a minimum 16 points improvement in the MDS-UPDRS-III after dopaminergic therapy.
• Patients who can undergo the stereotaxic surgery for Parkinson's disease due to the intolerable motor complication minimum score of 4 to a maximum score of 9 in the MDS-UPDRS-IV part B (diurnal fluctuation of symptom) , not responsive to optimal medical therapy.
• To be able to comply with the requirements, including the frequent clinical examination after medical treatment, in this study.
• To keep the therapeutic medicine for Parkinson's disease for at least 2 months prior to participation in this study.
• Written informed consent.

You may not qualify if:

• Patients who is suspected secondary / atypical parkinsonism based on the medical history of cerebral vascular disease, exposure to antipsychotic or toxic agents, and encephalitis or based on the symptom of Progressive supranuclear palsy, Pyramidal tract sign, autonomic sign, Dementia, Hallucination, Delusion and so on or based on the finding by magnetic resonance imaging (MRI) such as Lacunar infarct or atrophy of the midbrain tectum and atrophy of the pons and the cerebellum.
• Patients with history of 3 hours or more of intensive or violent dyskinesias in the past 6 months.
• Patients with previous the stereotaxy for Parkinson's disease (pallidotomy, thalamotomy, deep brain stimulation) .
• Mini-Mental State Examination (MMSE) ≤ 20 or patient with a diagnosis of dementia in the neuropsychological evaluation.
• Patients with medical history of Hallucination, Delusion, schizophrenia or affective disorder within 6 months of informed consent.
• Patients with history of significant cardiovascular disease including cerebrovascular accident.
• Malignant neoplasm in the brain, clinically significant neurological disease (for example significant brain atrophy not consistent with age).
• History of other malignancy, with the exception of treated carcinoma cutaneum, within 5 years.
• Uncontrolled hypertension: systolic blood pressure ≥ 160 mmHg.
• Coagulopathy or need for anticoagulant therapy.
• Clinically significant immune dysfunction (for example, the case who require the use of immunosuppressive drugs).
• Geriatric Depression Scale (GDS) short scale ≥ 10 points, or if on antidepressant, the score \> 5 points.
• On monoamine oxidase (MAO)-A inhibitors, or antipsychotic medications.
• Unable to scan MRI.
• Cases without abnormal finding in FMT-PET.

Sponsors & Collaborators

• Jichi Medical University: lead
• Takara Bio Inc.: collaborator
• Gene Therapy Research Institution,Co.,Ltd.: collaborator

Study Sites (1)

Jichi Medical University

Shimotsuke, Tochigi, 3290498, Japan

Location

MeSH Terms

Conditions

Parkinson Disease; Basal Ganglia Diseases; Brain Diseases

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Shin-ichi Muramatsu, MD, PhD

  Division of Oriental Medicine, Center for Community Medicine, Jichi Medical University; Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University; Division of Neurology, Department of Medicine, Jichi Medical University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 12, 2015
• First Posted: April 16, 2015
• Study Start: April 14, 2015
• Primary Completion: March 31, 2018
• Study Completion: March 31, 2018
• Last Updated: August 9, 2019

Record last verified: 2019-08

Locations

JP (1)