UMIN-CTR Clinical Trial

Public title

Exploratory Study of NS-089/NCNP-02 in Duchenne muscular dystrophy

Acronym

Exploratory Study of NS-089/NCNP-02

Scientific Title

Exploratory Study of NS-089/NCNP-02 in Duchenne muscular dystrophy

Scientific Title:Acronym

Exploratory Study of NS-089/NCNP-02

Region

Japan

Condition

Duchenne muscular dystrophy

Classification by specialty

Neurology

Pediatrics

Classification by malignancy

Others

Genomic information

YES

Narrative objectives1

This study is designed to assess the safety, tolerability, efficacy and pharmacokinetics (PK) of NS-089/NCNP-02 in subjects diagnosed with Duchenne muscular dystrophy (DMD), and to determine the dosage for subsequent studies.

Basic objectives2

Safety

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Explanatory

Developmental phase

Phase I,II

Primary outcomes

Safety (adverse event and adverse drug reaction)

Key secondary outcomes

1. Expression of dystrophin protein
2. Detection of exon 44-skipped mRNA of dystrophin
3. Time to Stand Test (TTSTAND)
4. Time to Run/Walk 10 Meters test (TTRW)
5. Six-Minute Walk Test (6MWT) and Two-Minute Walk Test (2MWT)
6. Timed Up & Go (TUG) test
7. Performance of Upper Limb (PUL) test
8. NS-089/NCNP-02 concentration of the blood plasma
9. NS-089/NCNP-02 concentration of the urine
10. Serum Creatine kinase concentration

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

Medicine

Interventions/Control_1

"[Part 1]
NS-089/NCNP-02 is administered at dose levels 1 and 3 in Cohort 1 (n=3) and at dose levels 2 and 4 in Cohort 2 (n=3)."
Dose level 1: 1.62 mg/kg once weekly for 2 weeks
Dose level 2: 10 mg/kg once weekly for 2 weeks
Dose level 3: 40 mg/kg once weekly for 2 weeks
Dose level 4: 80 mg/kg once weekly for 2 weeks
"[Part 2]
Based on the results from Part 1, two dosages are selected as study dosages in Part 2. Each selected dose are administered once a week for 24 weeks."

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

4

years-old

<=

Age-upper limit

17

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 44 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 etc), must be confirmed through these techniques by the time of visit 3.
2. DNA sequencing of exon 44 confirms that no DNA polymorphisms occur that could compromise duplex formation between NS-089/NCNP-02 and pre-mRNA.
3. Male and >= 8 years and < 17 years of age at the time of obtaining informed consent and/or assent. Subjects aged >= 4 years and < 8 years can be enrolled according to the circumstances.
4. 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.
5. Life expectancy of at least 1 year
6. Able to ambulate. Non-ambulant subject can be enrolled according to the circumstances.
7. Have intact muscles, which have adequate quality for biopsy. (No lacks or severe atrophy of biceps brachii or tibialis anterior muscle)
8. QTc <450 msec (based on 12-lead ECGs), or <480 msec for subject with Bundle Branch Block.
9. Glucocorticoid-naive patients, or patients who have used systemic glucocorticoids for at least 6 months prior to enrollment in this study with no dose changes for at least 3 months prior to enrollment.

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. Continuous use of artificial respirator (except for use of NPPV while sleeping)
4. A left ventricular ejection fraction (EF) < 40% or fractional shortening (FS) < 25% based on echocardiogram (ECHO).
5. Surgery within the last 3 months prior to the first anticipated administration of study medication or planned for anytime between visit 1 of Part 1 and the last visit of Part 2.
6. Positive hepatitis B surface antigen (HbsAg), hepatitis C antibody test (HCV), or human immunodeficiency virus (HIV) test at screening.
7. Current diagnosis of any immune deficiency or autoimmune disease.
8. Current diagnosis of any active or uncontrolled infection, cardiomyopathy, or liver or renal disease.
9. Use of any other investigational agents and/or experimental agents within 3 months prior to the first anticipated administration of study medication.
10. History of any severe drug allergy.

Target sample size

6

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

Name of contact person

1st name	Takami
Middle name
Last name	Ishizuka

Organization

National Center of Neurology and Psychiatry

Division name

Section of Clinical Research Suppor, Clinical Research and Education Promotion Division

Zip code

187-8551

Address

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

TEL

042-341-2711

Homepage URL

Email

tmc-crso@ncnp.go.jp

Institute

National Center of Neurology and Psychiatry

Institute

Department

Personal name

Organization

Japan Agency for Medical Research and Development

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Nippon Shinyaku Co., Ltd.

Name of secondary funder(s)

Organization

IRB, National Center of Neurology and Psychiatry

Address

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

Tel

042-341-2711

Email

irb-office@ncnp.go.jp

Secondary IDs

YES

Study ID_1

NCT04129294

Org. issuing International ID_1

ClinicalTrials.gov

Study ID_2

Org. issuing International ID_2

IND to MHLW

2019年10月7日

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）、鹿児島大学病院（鹿児島県）/Kagoshima University Hospital（Kagoshima）

Date of disclosure of the study information

2019

Year

11

Month

06

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

6

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

Completed

Date of protocol fixation

2019

Year

10

Month

04

Day

Date of IRB

2019

Year

10

Month

03

Day

Anticipated trial start date

2019

Year

11

Month

06

Day

Last follow-up date

2021

Year

12

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2019

Year

11

Month

06

Day

Last modified on

2022

Year

11

Month

07

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000043651