Status:
Recruiting
Clinicaltrials.gov identifier:
Sponsor:
Jichi Medical University
Enrollment:
6
Study Design:
This study is a phase 1/2 non-randomized, single center, open label, interventional, safety and dose evaluation study of the active agent AAV-hAADC-2 being delivered intra-putaminal via stereotaxic surgery. It is being conducted at the Jichi Medical University in Japan. The target putamen is identified on the pre-operative MRI brain and then bilateral putamina are infused with the active drug at a total of 4 spots (2 on each putamen). AAV-hAADC-2 is administered via bilateral intra-putaminal infusion in either low or high dose. There are two sequential study arms. Cohort 1 receives low dose (3x1011 vector genome/subject) and is infused with a total volume of 200 μl of the drug (50 μl per site). If there are no safety concerns at 6 months, then the study moves to cohort 2. Cohort 2 will receive high dose (9x1011 vector genome/subject) with 600 μl of total infusion volume (150 μl per site). The study includes patients with clinical diagnosis of idiopathic PD aged between 35 to 75 years of age with no other known or suspected cause of parkinsonism. Patients should be levodopa responsive and should have been on it for at least 5 years. An OFF state MDS-UPDRS score between 30–100 and Hoehn and Yahr stage IV is required. Patients with a history of 3 hours or more of intensive or violent dyskinesia are excluded from the study. Standard surgical exclusionary criteria are applied.
Rationale:
Primary outcome measures include assessment of safety of intra-putaminal infusion of AAV-hAADC-2 as measured by adverse events. Secondary outcomes include two measures: 1. The treatment effect of the drug at the end of 6 months. This is assessed by improvement in PD symptoms as recorded in subject diaries, clinical assessment and change in levodopa dosage. 2. The amount of intra-putaminal expression of AAV-hAADC-2 after 6 months, as measured by FMT-PET imaging. Investigators will continue to assess the safety for 5 years after baseline examination and long term follow up will continue for 10 years.
Comments:
This is a phase 1/2 dose escalation safety and efficacy study. No results have been published yet.
