NCT02418598

AADC Gene Therapy for Parkinson's Disease

A Phase I /II Study of Intra-putaminal Infusion of Adeno-Associated Virus Encoding Human Aromatic L-Amino Acid Decarboxylase in Subjects With Parkinson's Disease

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 2 (actual)
• Sponsor: Jichi Medical University · Academic / Other
• Sex: All
• Age: 35 Years – 75 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Subjects will be hospitalized and conducted the baseline examination on Day -10. 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 / 600 µL at a total of 4 sites (2 sites in left putamen, 2 sites in right putamen; 50 / 150 µL per site) at a flow rate of 3 µL per minute on Day 0. After the infusion is complete, the cannula devices will be removed, and the surgical incision will be seamed in accordance with usual trephination. After that, cranial CT scan will be performed so as to confirm whether there are complications such as the occurrence of intracranial bleeding or not. Subjects stay in a hospital for 14 days after infusion of AAV-hAADC-2. Data and Safety Monitoring Board (DSMB) will be evaluated the safety and efficacy of all subjects at 6 months later assessment in low dose cohort. If there are no events relevant to the discontinuance criteria or moderate to severe adverse events with casual relationship, "Definitely related" or "Possibly related", to AAV-hAADC-2 in this cohort, the study moves to high dose cohort. At the time of 6 months after the infusion, investigator assesses the treatment effect of AAV-hAADC-2 on the basis of subject diaries, clinical assessment and levodopa requirement dosage. At the same time, investigator assesses a relationship between the dose of AAV-hAADC-2 infused and the amount of intra-putaminal expression by FMT-PET imaging. The investigator also assesses the safety for 5 years after the baseline examination. Long-term follow up study is additionally conducted for 10 years in reference to guideline of FDA.

Conditions

• Parkinson Disease

Interventions

Type	Name	Description
GENETIC	Cohort1	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.
GENETIC	Cohort2	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.

Timeline

• Start date: 2015-04-14
• Primary completion: 2018-03-31
• Completion: 2018-03-31
• First posted: 2015-04-16
• Last updated: 2019-08-09

Locations

1 site across 1 country: Japan