UMIN-CTR Clinical Trial

Public title

A multicentre trial of KN01 in patients with mitochondrial encephalomyopathy (MELAS)

Acronym

MELAS-taurine study

Scientific Title

A multicentre trial of KN01 in patients with mitochondrial encephalomyopathy (MELAS)

Scientific Title:Acronym

MELAS-taurine study

Region

Japan

Condition

motochondrial encephalomyopathy (MELAS)

Classification by specialty

Neurology

Classification by malignancy

Others

Genomic information

YES

Narrative objectives1

To investigate the effocacy and safety of taurine supplementation therapy for prevention of stroke-like episodes in patients with MELAS

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Developmental phase

Phase III

Primary outcomes

(1) efficacy: 100% respondor rate
(2) safety: adverse events and adverse effects

Key secondary outcomes

(1) Japan Mitochondrial Disease Rating Scale
(2) 50% responder rate
(3) the number of abrupt-onset focal neurological deficits
(4) the levels of lactate, pyruvate and taurine in the blood and CSF
(5) brain MRI study
(6) the number of uses intravenous formulation with L-arginine
(7) the number of times in which high intensity lesions detected by brain MRI

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

Prevention

Type of intervention

Medicine

Interventions/Control_1

taurine supplementation

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

Not applicable

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

(1) patients comprehensively diagnosed with MELAS based on clinical manifestations, muscle pathological findings, and genetic testing, as followed by the diagnostic criteria of MELAS
(2) patients with point mutations of either A3243G, T3271C, G3244A, T3258C, or T3291C in the mitochondrial DNA
(3) age at the time of obtaining informed consent , gender , hospitalization or outpatient are unquestioned
(4) patients not using arginine for 78 weeks before obtaining informed consent, or patients continuously using arginine for at least 26 weeks before obtaining informed consent
(5) patients who meet any of the following:
1) patients without arginine use should have stroke-like episodes more than twice in 78 weeks and more than once in 52 weeks before obtaining informed consent (no arginine combination cases )
2) patients with arginine use who meet any of the following, depending on the period of arginine use (arginine combination cases)

If (i) arginine use period within 78 weeks, patients should have stroke-like episodes more than twice in the period of use and at least more than once in 52 weeks before obtaining informed consent
If (ii) arginine use period exceeds 78 weeks, patients should have stroke-like episodes more than twice in 78 weeks and at least more than once in 52 weeks before obtaining informed consent

The definition of stroke-like episodes in the selection criteria , includes any of the following paroxysmal focal neurological symptoms of 1) ~ 6), and
the implementation of the head MRI does not matter .
1) hemiparesis or monoparesis
2) cortical sensory impairment ( sensory extinction )
3) cortical visual impairment (scintilating scotoma, cortical blindness)
4) aphasia
5) apraxia
6) agnosia

(6) patient that has not been treated with oral taurine supplementation
(7) patient capable of being evaluated by clinical findings of stroke-like episodes

Key exclusion criteria

(1) patients can not be conducted by head MRI scan because of pacemaker implantation, etc.
(2) patients with severe coma or status epileptics
(3) patients incapable of communication due to dementia, bedridden, etc.,
(4) patients with merger sepsis
(5) patients with severe impairment in cardiac, liver, or renal function
(6) patients in need of systemic administration of steroids for a long period of time (2 weeks or more)
(7) patients with pyruvate in 12 weeks before obtaining informed consent
(8) patients who are pregnant or lactating, or may be pregnant
(9) patients with history of hypersensitivity to the component of study drug
(10) patients with history of drug allergy
(11) patients who participated in clinical trials within 12 weeks before obtaining informed consent
(12) other, patients whom physician or investigator has determined disqualified as participants

Target sample size

15

Name of lead principal investigator

1st name
Middle name
Last name	Yoshihide Sunada

Organization

Kawasaki Medical School

Division name

Neurology

Zip code

Address

577 Matsushima,Kurashiki-city,Okayama 701-0192 Japan

TEL

086-462-1111

Email

ysunada@med.kawasaki-m.ac.jp

Name of contact person

1st name
Middle name
Last name	Mai Moriyama

Organization

CTD inc.

Division name

Medicinal Products Promotion Division

Zip code

Address

3-3-2, Tsukiji, Chuo-ku, Tokyo

TEL

03-6228-4105

Homepage URL

https://www.c-ctd.co.jp/project_sn01/researcher/contents/documents.html

Email

taurine@c-ctd.co.jp

Institute

Kawasaki Medical School Hospital

Institute

Department

Personal name

Organization

Ministry of Health, Labour and Welfare

Organization

Division

Category of Funding Organization

Japanese Governmental office

Nationality of Funding Organization

Co-sponsor

National Defense Medical College Hospital
Seirei Hamamatsu General Hospital
Fujita Health University School of Medicine
National Hospital Organization Kyoto Medical Center
Hyogo-Chuo National Hospital
Fukuoka University Chikushi Hospital
Kurume University Hospital
Nagasaki University Hospital
Hiroshima University Hospital
Nippon Medical School
National Center of Neurology and Psychiatry
Teikyo University of Science

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

9月13日

Institutions

川崎医科大学附属病院/Kawasaki Medical School
防衛医科大学校病院/National Defense Medical College Hospital
聖隷浜松病院/Seirei Hamamatsu General Hospital
藤田保健衛生大学病院/Fujita Health University School of Medicine
独立行政法人国立病院機構京都医療センター/National Hospital Organization Kyoto Medical Center
独立行政法人国立病院機構兵庫中央病院/Hyogo-Chuo National Hospital
福岡大学筑紫病院/Fukuoka University Chikushi Hospital
久留米大学医学部附属病院/Kurume University Hospital
長崎大学病院/Nagasaki University Hospital
広島大学病院/Hiroshima University Hospital

Date of disclosure of the study information

2013

Year

09

Month

30

Day

URL releasing protocol

https://www.c-ctd.co.jp/project_sn01/researcher/contents/documents.html

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Look at the attached file, "clinical trial report"

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

Completed

Date of protocol fixation

2013

Year

07

Month

24

Day

Date of IRB

Anticipated trial start date

2013

Year

10

Month

03

Day

Last follow-up date

2015

Year

01

Month

09

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

2015

Year

03

Month

31

Day

Other related information

Registered date

2013

Year

09

Month

30

Day

Last modified on

2019

Year

02

Month

25

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000013908