Clinical research of the gene therapy for AADC deficiency

UMIN ID: UMIN000017802

Registered date:04/06/2015

Basic Information

• Recruitment status: Open public recruiting
• Health condition(s) or Problem(s) studied: AADC deficiency
• Date of first enrollment: 2015/06/04
• Target sample size: 5
• Countries of recruitment: Japan
• Study type: Interventional

Intervention(s)

Subjects will be hospitalized before Day -14 and conducted the baseline examination. The target putmen 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 micro L at a total of 4 sites (2 sites in left putamen, 2 sites in right putamen; 50 micro L per site) at a flow rate of 3 micro L 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 efficacy of all subjects and safety of the treatment.
At the time of 6 months after the infusion, investigator assesses the treatment effect of AAV-hAADC-2 on the basis of clinical assessment and 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.

Outcome(s)

Primary Outcome

Safety of the AAV-hAADC-2 injection therapy into the Putamen of the patients with AADC deficiency.
･ Adverse event
･Clinical records of seizure, physical findings, and neurological findings.
･Laboratory findings, cerebro- spinal fluid examination, cranial MRI, and EEG.

Key inclusion & exclusion criteria

• Age minimum: 4years-old
• Age maximum: Not applicable
• Gender: Male and Female

Include criteria

1.Typical AADC deficiency patients who was unable to stand with motor disturbance and dystonia. Diagnosis was confirmed from the findings of CSF analysis, enzyme activity or genetic analysis.
2.Age; => 4 years at the time of medical treatment. No restriction of age upper limit.
3.No findings suggestive of CNS Degenerative Disease are found.
4.To be able to comply with the requirements of this study, including the frequent clinical examination after medical treatment.
5.To keep the therapeutic medicine for AADC deficiency for at least 2 months prior to participation in this study.
6.Written informed consent from patient' s parental authorities.

Exclude criteria

1.Mild AADC deficiency patients who can stand and walk.
2.Patients with history of significant cardiovascular disease including cerebrovascular accident.
3.Malignant neoplasm in the brain, clinically significant neurological disease.
4.History of malignancy, with the exception of treated carcinoma cutaneum, within 5 years.
5.Uncontrolled hypertension: systolic blood pressure over 160 mmHg.
6.Coagulopathy or need for anticoagulant therapy.
7.Clinically significant immune dysfunction (for example, the case who require the use of immunosuppresive drugs).
8.Unable to scan MRI.
9.Cases without abnormal finding in FMT-PET.
10.Past medical history of serious drug allergy.
11.Patients who have participated in other clinical trial within 6 months.
12.Patients who meet any of the following criteria:
a) Serious renal disorder (Cr; => 2.0 mg/dl, and BUN; => 25mg/dl)
b) Serious hepatic disorder AST (GOT) / ALT (GPT) ; => 2.5 x upper limit of normal (ULN)
c) Serious diabetes (casual blood glucose or fasting blood glucose; => 200 mg/dl and HbA1c; => 9 %)
13.Seriously ill patients
14.Any other patients judged by investigators to be inappropriate for the subject of this study.

Related Information

• Primary Sponsor: JIchi Medical University
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development