UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	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
Title of the study (Brief title)	AADC Gene Therapy for Parkinson's Disease
Region	Japan

Condition
Condition	Advanced Parkinson's Disease
Classification by specialty	Neurology
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	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.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Pragmatic
Developmental phase	Phase I,II

Assessment
Primary outcomes	The safety of intra-putaminal infusion of AAV-hAADC-2 in patients with advanced Parkinson's disease
Key secondary outcomes	1.The efficacy of intra-putaminal infusion of AAV-hAADC-2 in patient, which is judged based on the symptom diary, the clinical evaluation and the required dose of L-dopa 2.The expression level of the AAV-hAADC-2 injected intra-putaminaly, which is judged by FMT-PET

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Gene
Interventions/Control_1	Cohort 1: 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 micro L at a total of 4 sites (2 sites in left putamen, 2 sites in right putamen; 50 maicro L per site) at a flow rate of 3 maicro L per minute on Day 0. The number of vector genomes (vg) administered in this cohort is 3x10^11 vg/subject. Cohort 2: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 micro L at a total of 4 sites (2 sites in left putamen, 2 sites in right putamen; 150 micro L per site) at a flow rate of 3 micro L per minute on Day 0. The number of vector genomes (vg) administered in this cohort is 9x10^11 vg/subject.
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	35 years-old <=
Age-upper limit	75 years-old >=
Gender	Male and Female
Key inclusion criteria	1.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. 2.Age<_75 years at the time of medical treatment. 3.Age at onset>_35 years. 4.Duration of L-dopa therapy>_5 years. 5.Hoehn and Yahr Stage IV in OFF state at the onset of medical treatment. 6.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. 7.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. 8.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. 9.To be able to comply with the requirements, including the frequent clinical examination after medical treatment, in this study. 10.To keep the therapeutic medicine for Parkinson's disease for at least 2 months prior to participation in this study. 11.Written informed consent.
Key exclusion criteria	1.Patients who is suspected secondary/atypical parkinsonism . 2.Patients with history of 3 hours or more of intensive or violent dyskinesias in the past 6 months. 3.Patients with previous the stereotaxy for Parkinson's disease. 4.MMSE<_20 or patient with a diagnosis of dementia in the neuropsychological evaluation. 5.Patients with medical history of Hallucination, Delusion, schizophrenia or affective disorder within 6 months of informed consent. 6.Patients with history of significant cardiovascular disease including cerebrovascular accident. 7.Malignant neoplasm in the brain, clinically significant neurological disease. 8.History of other malignancy, with the exception of treated carcinoma cutaneum, within 5 years. 9.Uncontrolled hypertension. 10.Coagulopathy or need for anticoagulant therapy. 11.Clinically significant immune dysfunction. 12.GDS short scale>_10 points, or if on antidepressant, the score>_5 points. 13.On MAO-A inhibitors, or antipsychotic medications. 14.Unable to scan MRI. 15.Cases without abnormal finding in FMT-PET. 16.Premenopausal female or male who desire impregnating a female. 17.Past medical history of convulsive seizure within 3 years or receiving antiepileptic drug or patients with epileptic aberrance in the electroencephalography. 18.Past medical history of serious drug allergy. 19.Patients who have participated in other clinical trial within 6 months. 20.Patients who meet any of the following criteria: a)Serious renal disorder b)Serious hepatic disorder c)Serious diabetes 21.Any other patients judged by investigators to be inappropriate for the subject of this study.
Target sample size	6

Research contact person
Name of lead principal investigator	Shinichi Muramatsu
Organization	Jichi Medical University
Division name	Department of Medicine, Division of Neurology
Address	311-1 Yakushiji, Shimono-shi, Tochigi, Japan
TEL	+81-285-58-7352
Email	muramats@jichi.ac.jp

Public contact
Name of contact person	Shinichi Muramatsu
Organization	Department of Medicine
Division name	Division of Neurology
Address	3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan
TEL	+81-285-58-7352
Homepage URL
Email	muramats@jichi.ac.jp

Sponsor
Institute	Jichi Medical University
Institute
Department

Funding Source
Organization	Gene Therapy Research Institution Co., Ltd
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor	Takara Bio Inc.
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	YES
Study ID_1	NCT02418598
Org. issuing International ID_1	Clinical Trial gov.
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	自治医科大学附属病院（栃木県） Jichi Medical University Hospital(Tochigi)

Other administrative information
Date of disclosure of the study information	2015 Year 05 Month 01 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2014 Year 10 Month 10 Day
Anticipated trial start date	2015 Year 04 Month 20 Day
Last follow-up date	2017 Year 12 Month 31 Day
Date of closure to data entry	2017 Year 12 Month 31 Day
Date trial data considered complete	2017 Year 12 Month 31 Day
Date analysis concluded	2018 Year 03 Month 31 Day

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2015 Year 05 Month 01 Day
Last modified on	2018 Year 05 Month 03 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000019994