Phase I/II Study of Gene Therapy for Parkinson's disease

JRCT ID: jRCT2033210696

Registered date:26/03/2022

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Parkinson's disease
• Date of first enrollment: 13/09/2022
• Target sample size: 12
• Study type: Interventional
• Intervention(s): AAV-hAADC-2 is designed to be injected into the striatum (putamen) of the patients with Parkinson's disease, according to the stereotactic neurosurgical method.

Outcome(s)

• Primary Outcome: To examine the safety and efficacy in patients with Parkinson's disease, after intracerebral administrations of AAV-hAADC-2 into the putamen.
• Secondary Outcome: To examine the efficacy in patients with Parkinson's disease, after intracerebral administrations of AAV-hAADC-2 into the putamen.

Key inclusion & exclusion criteria

• Age minimum: >= 40age old
• Age maximum: <= 75age old
• Gender: Both

Include criteria

-Patients diagnosed with Parkinson's disease by MDS Clinical Diagnostic Criteria for Parkinson's Disease.
-Patients aged 40 to 75 years at the time of obtaining informed consent.
-Patients onset of an illness> 35 years of age.
-Patients who have received L-dopa for at least 5 years.
-Patients whose severity of Hoehn & Yahr in the OFF state at the time of informed consent was IV.
-Patients with a baseline total MDS-UPDRS-III score (OFF) of 30 to 100.
-Patients who have a clear response to L-dopa and have improved MDS-UPDRS-III by at least 16 points at baseline ON and OFF.
-Untolerable motor complications in patients with a total score of at least 4 on MDS-UPDRS-IV at baseline (motor fluctuations) who fail to respond satisfactorily to appropriate drug therapy.
-Patients who can undergo stereotactic brain surgery.
-Patients who do not need dosage changes for the Parkinson's Disease treatment for at least 8 weeks, prior to the start of the study substance administration.

Exclude criteria

-Patients with a history of cerebrovascular disease, exposure to antipsychotics or toxins, encephalitis, symptoms such as progressive supranuclear palsy or cerebellar symptoms, pyramidal signs, autonomic signs, dementia, hallucinations or delusions, or MRI findings such as lachner infarction or atrophy of the midbrain tegment, pons and cerebellum suggesting secondary or atypical parkinsonism.
-Patients who have already undergone stereotactic neurosurgery (pallidal coagulation, thalamic coagulation, deep brain stimulation) and MR-guided focused ultrasound therapy for Parkinson's disease.
-Patients with a Mini-Mental State Examination (MMSE) score of 20 or less or with a diagnosis of dementia.
-Patients with a history of schizophrenia or affective disorders.
-Patients with apparent vascular diseases, including cerebrovascular disorders.
-Patients with neoplastic disease of the central nervous system, clinically evident neurological disease (e.g., age-inappropriate, obvious brain atrophy).
-Patients with a concomitant malignancy or a history of other malignancies other than previously treated skin cancers within 5 years before obtaining informed consent.
-Patients with uncontrolled hypertension.
-Patients with coagulopathy or who require antithrombotic therapy.
-Patients with clinically prominent evidence of immunodeficiency who require immunosuppressant treatments excluding steroid therapy.
-Patients with a score of 10 or more on the Geriatric Depression Scale-short form (GDS-S) or 5 or more on antidepressants.
-Patients who cannot undergo MRI.
-Individuals who wish to have children, but do not cryopreserve sperm or eggs prior to administration of the investigational product and use them to obtain children.
-Patients with a history of convulsive seizures within 3 years, those taking antiepileptic drugs, or those with abnormal electroencephalograms showing epileptic abnormalities.
-Patients with the following complications that are hard to manage.
1.Patients with severe renal disorders of the magnitude of both the serum creatinine levels of > 2.0 mg/dl and BUN>25 mg/dl.
2.Patients with severe hepatic disorders of the magnitude of either AST/GOT or ALT/GPT is above 2.5 folds of the upper limit of the normal levels.
3.Patients with diabetes of the magnitude of both >200 mg/dl casual or postprandial blood glucose levels and >9% HbA1c.

Related Information

• Primary Sponsor: Nakajima Takeshi
• Secondary Sponsor: Gene Therapy Research Institution Co., Ltd.