UMIN-CTR Clinical Trial

Unique ID issued by UMIN UMIN000017377
Receipt number R000019994
Scientific Title 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
Date of disclosure of the study information 2015/05/01
Last modified on 2018/05/03 10:52:35

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Basic information

Public title

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

Acronym

AADC Gene Therapy for Parkinson's Disease

Scientific Title

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

Scientific Title:Acronym

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

1st name
Middle name
Last name Shinichi Muramatsu

Organization

Jichi Medical University

Division name

Department of Medicine, Division of Neurology

Zip code


Address

311-1 Yakushiji, Shimono-shi, Tochigi, Japan

TEL

+81-285-58-7352

Email

muramats@jichi.ac.jp


Public contact

Name of contact person

1st name
Middle name
Last name Shinichi Muramatsu

Organization

Department of Medicine

Division name

Division of Neurology

Zip code


Address

3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan

TEL

+81-285-58-7352

Homepage URL


Email

muramats@jichi.ac.jp


Sponsor or person

Institute

Jichi Medical University

Institute

Department

Personal name



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)



IRB Contact (For public release)

Organization


Address


Tel


Email



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


Related information

URL releasing protocol


Publication of results

Unpublished


Result

URL related to results and publications


Number of participants that the trial has enrolled


Results


Results date posted


Results Delayed


Results Delay Reason


Date of the first journal publication of results


Baseline Characteristics


Participant flow


Adverse events


Outcome measures


Plan to share IPD


IPD sharing Plan description



Progress

Recruitment status

Completed

Date of protocol fixation

2014 Year 10 Month 10 Day

Date of IRB


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


Other

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

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000019994


Research Plan
Registered date File name

Research case data specifications
Registered date File name

Research case data
Registered date File name