UMIN-CTR Clinical Trial

Public title

Kyoto Trial to Evaluate the Safety and Efficacy of iPSC-derived dopaminergic progenitors in the treatment of Parkinson's Disease

Acronym

Kyoto Trial to Evaluate the Safety and Efficacy of iPSC-derived dopaminergic progenitors in the treatment of Parkinson's Disease

Scientific Title

Kyoto Trial to Evaluate the Safety and Efficacy of iPSC-derived dopaminergic progenitors in the treatment of Parkinson's Disease

Scientific Title:Acronym

Kyoto Trial to Evaluate the Safety and Efficacy of iPSC-derived dopaminergic progenitors in the treatment of Parkinson's Disease

Region

Japan

Condition

Parkinson's disease

Classification by specialty

Neurology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To evaluate the safety and efficacy of transplantation of human induced pluripotent stem cell-derived dopaminergic progenitors into the corpus striatum in patients with Parkinson's disease

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Developmental phase

Phase I,II

Primary outcomes

1) Incidence and severity of adverse events
2) Presence or absence of graft expansion in the brain at 24 months after transplantation

Key secondary outcomes

<Safety endpoints>
1) Uptake of [18F]FLT
2) Uptake of [18F]GE180
3) Dyskinesia score
4) Graft size (MRI)

<Efficacy endpoints>
1) MDS-UPDRS Part III total score (at ON and OFF times)
2) MDS-UPDRS Part II total score
3) MDS-UPDRS Part I total score
4) Sum score of MDS-UPDRS Part I, Part II, and Part III (at ON and OFF times)
5) Average daily ON duration (with or without dyskinesia) and OFF duration
6) Bradykinesia subscale
7) Uptake of [18F]FDOPA
8) Uptake on DAT scan
9) Parkinson's Disease Questionnaire (PDQ-39)
10) Hoehn and Yahr severity
11) L-dopa equivalent dose
12) Euro-QOL 5 Dimensions-5 Levels (EQ-5D-5L)
13) Work Productivity and Activity Impairment Questionnaire (WPAI)
14) Nursing care category

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Other

Interventions/Control_1

Under general anesthesia using a stereotactic brain surgery system, human iPSC-derived dopaminergic progenitors will be transplanted into the bilateral putamen. For the first 3 patients, approximately 2.4X10^6 cells will be delivered at each side. For the 4th and later patients, 4.2-5.4X10^6 cells will be transplanted at each side.
Immunosuppressant treatment will be started in the morning on the day of transplantation, continued until 52 weeks after transplantation, and then tapered off to zero over 12 weeks. In the early phase, the immunosuppressant is orally administered 0.03 to 0.15 mg/kg, twice a day, and the targeted blood concentration is within a range of 5-10 ng/mL as a trough value.

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

Age-lower limit

50

years-old

<=

Age-upper limit

70

years-old

>

Gender

Male and Female

Key inclusion criteria

1)The patient has a diagnosis of PD (clinically established or clinically probable) in accordance with the MDS Clinical Diagnostic Criteria for Parkinson's Disease (2015).
2)The patient plans to undergo transplantation of human iPSC-derived dopaminergic progenitors.
3)The patient has a poor response to existing drug treatments.
4)The patient is >= 50 years and < 70 years of age at the time of informed consent.
5)The patient has had PD for at least 5 years.
6)The patient has both ON and OFF (as demonstrated by the MDS-UPDRS Part III and a symptom diary).
7)The patient is in stage 3 or higher on the Hoehn and Yahr scale at OFF time.
8)The patient is in stage 3 or lower on the Hoehn and Yahr scale at ON time.
9)The patient has an L-dopa response of 30% or more without influence of antiparkinsonian drugs.
10)The patient has a decrease pattern characteristic to PD in the basal ganglia region on DAT scan.
11)The patient has the following organ functions as determined by laboratory tests within 7 days before registration:
i)Neutrophil count >= 2,000/microL
ii)Platelet count >= 5.0 X 10^4/microL
iii)AST, ALT =< 3.0 X upper limit of normal at the study site
iv)Total bilirubin =< 1.5 X upper limit of normal at the study site
v)eGFR >= 60 mL/min/1.73 m2
vi)eGFR (mL/min/1.73 m2) = 194 X Cr^-1.094 X age^-0.287 (X 0.739 for females)
12)The patient provides written informed consent to participate in the study.
A patient who cannot write due to the disease may be enrolled if he or she provides verbal consent and a witness signs the informed consent form.

Key exclusion criteria

1)The patient has a symptomatic organic lesion as detected by head MRI.
2)The patient has abnormal immune function.
3)The patient is demented or deemed at high risk of dementia.
4)The patient has bleeding tendency or abnormal coagulation function.
5)The patient is HBs antigen-positive, or HBs antibody- or HBc antibody-positive with evidence of HBV-DNA.
6)The patient is anti-HIV antibody-positive.
7)The patient is anti-HTLV-1 antibody-positive.
8)The patient has active infection such as hepatitis C or syphilis (STS/TPHA).
9)The patient has contraindication to the study drug (tacrolimus), concomitant drugs (e.g., levodopa, carbidopa, MRI contrast), and/or their components.
10)The patient has hypersensitivity to the study drug (tacrolimus), concomitant drugs (e.g., levodopa, carbidopa, MRI contrast), and/or their components.
11)The patient has severe allergic to gentamicin, a bovine-derived ingredient l or a pig-derived ingredient.
12)The patient has undergone transplantation of human iPSC-derived dopaminergic progenitors.
13)The patient has any of the following diseases concurrently:
.Malignant neoplasm
.Epilepsy
.Mental disease (e.g., depression, bipolar disorder, schizophrenia)
.Other serious concurrent diseases (e.g., cerebrovascular disorder, heart disease, chronic respiratory disease, inadequately controlled hypertension, diabetes mellitus)
14)The patient has a history of any of the following:
.Malignant neoplasm
.Epilepsy
.Cerebral hemorrhage
.Mental disease (e.g., depression, bipolar disorder, schizophrenia)
.Pallidotomy, thalamotomy, or deep brain stimulation
15)The patient is pregnant or lactating, or does not agree to avoid pregnancy throughout the study.
16)The patient, in the opinion of the investigator or subinvestigator, is not appropriate to conduct the study safely.

Target sample size

7

Name of lead principal investigator

1st name	Ryosuke
Middle name
Last name	Takahashi

Organization

Kyoto University Hospital

Division name

Department of Neurology

Zip code

606-8507

Address

54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507

TEL

075-751-3771

Email

neuroofc@kuhp.kyoto-u.ac.jp

Name of contact person

1st name	Nobukatsu
Middle name
Last name	Sawamoto

Organization

Kyoto University Hospital

Division name

Department of Neurology

Zip code

606-8507

Address

54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507

TEL

075-751-3771

Homepage URL

Email

neuroofc@kuhp.kyoto-u.ac.jp

Institute

Kyoto University Hospital

Institute

Department

Personal name

Organization

Japan Agency for Medical Research and Development

Organization

Division

Category of Funding Organization

Government offices of other countries

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Sumitomo Dainippon Pharma Co., Ltd.

Organization

Kyoto University Hospital Institutional Review Board

Address

54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, JAPAN

Tel

075-751-4389

Email

tiken@kuhp.kyoto-u.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

初回届出年月日：2018年6月4日　　届出回数：第1回

Institutions

京都大学医学部附属病院（京都府）

Date of disclosure of the study information

2018

Year

07

Month

31

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

7

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

Recruitment status

No longer recruiting

Date of protocol fixation

2018

Year

04

Month

06

Day

Date of IRB

2018

Year

05

Month

08

Day

Anticipated trial start date

2018

Year

08

Month

01

Day

Last follow-up date

2023

Year

12

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2018

Year

07

Month

30

Day

Last modified on

2023

Year

08

Month

04

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000038278