UMIN-CTR Clinical Trial

Unique ID issued by UMIN	UMIN000010964
Receipt number	R000012799
Scientific Title	Exploratory Study of NS-065/NCNP-01 in Duchenne muscular dystrophy
Date of disclosure of the study information	2013/06/17
Last modified on	2021/07/01 17:33:31

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Basic information

Public title

Exploratory Study of NS-065/NCNP-01 in Duchenne muscular dystrophy

Acronym

Exploratory Study of NS-065/NCNP-01

Scientific Title

Exploratory Study of NS-065/NCNP-01 in Duchenne muscular dystrophy

Scientific Title:Acronym

Exploratory Study of NS-065/NCNP-01

Region

Japan

Condition

Duchenne muscular dystrophy

Classification by specialty

Neurology Pediatrics

Classification by malignancy

Others

Genomic information

YES

Objectives

Narrative objectives1

The purpose of this study is to evaluate safety of NS-065/NCNP-01, to elucidate its pharmacokinetics and to explore biomarkers related to its efficacy against Duchenne muscular dystrophy.

Basic objectives2

Safety

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Explanatory

Developmental phase

Phase I

Assessment

Primary outcomes

Safety (adverse event and adverse drug reaction)

Key secondary outcomes

1. Expression of dystrophin protein
2. Detection of exon53 skipped mRNA of dystrophin
3. NS-065/NCNP-01 concentration of the blood plasma
4. NS-065/NCNP-01 concentration of the urine
5. Serum Creatine kinase concentration

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

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Cohort 1: NS-065/NCNP-01 1.25 mg/kg once weekly for 12 weeks (n=3)
Cohort 2: NS-065/NCNP-01 5.0 mg/kg once weekly for 12 weeks (n=3)
Cohort 3: NS-065/NCNP-01 20.0 mg/kg once weekly for 12 weeks (n=3 or 4)

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

5 years-old <=

Age-upper limit

18 years-old >

Gender

Male

Key inclusion criteria

Subject with Duchenne muscular dystrophy eligible for enrolment in the study must meet all of the following criteria:

1) Has an out of frame deletion(s) that could be corrected by skipping exon 53 as confirmed by any of methodology at the time of visit 1. If not confirmed by any of methodology that evaluates the relative copy number of all exons (i.e. MLPA, CGH etc), must be confirmed through these techniques by the time of visit 4.
2) DNA sequencing of exon 53 confirms that no DNA polymorphisms occur that could compromise duplex formation between NS-065/NCNP-01 and pre-mRNA.
3) There is confirmation of detection of dystrophin mRNA with skipping of exon 53 and dystrophin production after in vitro exposure of NS-065/NCNP-01 to subject-derived cells.
4) Male and >= 5 years and < 18 years of age at the time of obtaining informed consent and/or assent.
5) Able to give informed consent in writing signed by parent(s) or legal guardian who is able to understand all of the study procedure requirements. If applicable, able to give informed assent in writing signed by the subject.
6) Life expectancy of at least 1 year
7) Unable to ambulate. Ambulant subject can be enrolled according to the circumstances.
8) Have intact muscles, which have adequate quality for biopsy.
(No lacks or severe atrophy of tibialis anterior muscle)
9) QTc <450 msec (based on 12-lead ECGs), or <480 msec for subject with Bundle Branch Block.
10) If taking glucocorticosteroids, no significant change in total daily dosage or dosing regimen after the time of visit 1.

Key exclusion criteria

Subject with Duchenne muscular dystrophy meeting any of the following criteria must not be enrolled in the study:

1)Has participated in other pharmacological clinical trial that might recover dystrophin protein by the readthrough or the exon-skipping therapy, and/or upregulate the dystrophin-associated proteins such as utrophin.
2) A forced vital capacity (FVC) < 50% of predicted.
3) A left ventricular ejection fraction (EF) < 40% or fractional shortening (FS) < 25% based on echocardiogram (ECHO).
4) Surgery within the last 3 months prior to the first anticipated administration of study medication or planned for anytime during the duration of the study.
5) Positive hepatitis B surface antigen (HbsAg), hepatitis C antibody test (HCV), or human immunodeficiency virus (HIV) test at screening.
6) Current diagnosis of any immune deficiency or autoimmune disease.
7) Current diagnosis of any active or uncontrolled infection, cardiomyopathy, or liver or renal disease.
8) Use of any other investigational agents and/or experimental agents within 3 months prior to the first anticipated administration of study medication.
9) History of any severe drug allergy.
10) Unable to give informed consent about using adequate contraception from the first administration until at least 6 months after the last dose of study medication, by parent(s) or legal guardian.
11) Subject considered by the investigator (or sub-investigator), for any reason, to be an unsuitable candidate for the study.

Target sample size

Research contact person

Name of lead principal investigator

1st name Hirofumi

Middle name

Last name Komaki

Organization

National Center of Neurology and Psychiatry

Division name

Department of Child Neurology, National Center Hospital

Zip code

187-8551

Address

4-1-1, Ogawa-higashi, Kodaira, Tokyo 187-8551, Japan

TEL

042-341-2711

Email

komakih@ncnp.go.jp

Public contact

Name of contact person

1st name Maki

Middle name

Last name Ohata

Organization

National Center of Neurology and Psychiatry

Division name

Clinical Research Unit, National Center Hospital

Zip code

187-8551

Address

4-1-1, Ogawa-higashi, Kodaira, Tokyo 187-8551, Japan

TEL

042-341-2711

Homepage URL

Email

chiken5@ncnp.go.jp

Sponsor or person

Institute

National Center of Neurology and Psychiatry

Institute

Department

Personal name

Funding Source

Organization

Ministry of Health, Labour and Welfare

Organization

Division

Category of Funding Organization

Japanese Governmental office

Nationality of Funding Organization

Other related organizations

Co-sponsor

Nippon Shinyaku Co., Ltd.

Name of secondary funder(s)

Nippon Shinyaku Co., Ltd.

IRB Contact (For public release)

Organization

National Center of Neurology and Psychiatry

Address

4-1-1, Ogawa-higashi, Kodaira, Tokyo 187-8502, Japan

Tel

042-341-2711

Email

irb-office@ncnp.go.jp

Secondary IDs

YES

Study ID_1

NCT02081625

Org. issuing International ID_1

ClinicalTrials.gov

Study ID_2

Org. issuing International ID_2

IND to MHLW

2013年5月13日(初回届)

Institutions

国立研究開発法人国立精神・神経医療研究センター（東京都）/National Center of Neurology and Psychiatry（Tokyo）

Other administrative information

Date of disclosure of the study information

2013 Year 06 Month 17 Day

Related information

URL releasing protocol

https://stm.sciencemag.org/content/10/437/eaan0713.short

Publication of results

Published

Result

URL related to results and publications

https://stm.sciencemag.org/content/10/437/eaan0713.short

Number of participants that the trial has enrolled

Results

Komaki.H, Nagata.T, Saito.T, Masuda.S, Takeshita.E, Sasaki.M, Tachimori.H, Nakamura.H, Aoki.Y, Takeda.S Systemic administration of the antisense oligonucleotide NS-065/NCNP-01 for skipping of exon 53 in patients with Duchenne muscular dystrophy. Sci Transl Med. 2018, 10(437) https://stm.sciencemag.org/content/10/437/eaan0713.short

Results date posted

2021 Year 07 Month 01 Day

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

2013 Year 06 Month 13 Day

Date of IRB

2013 Year 05 Month 13 Day

Anticipated trial start date

2013 Year 06 Month 17 Day

Last follow-up date

2014 Year 12 Month 31 Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other

Other related information

Management information

Registered date

2013 Year 06 Month 14 Day

Last modified on

2021 Year 07 Month 01 Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000012799

Research Plan
Registered date	File name

Research case data specifications
Registered date	File name

Research case data
Registered date	File name