UMIN-CTR Clinical Trial

Basic information
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
Condition	Duchenne muscular dystrophy
Classification by specialty	Neurology Pediatrics
Classification by malignancy	Others
Genomic information	YES

Objectives
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

Assessment
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

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	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

Eligibility
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

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 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

Sponsor
Institute	National Center of Neurology and Psychiatry
Institute
Department

Funding Source
Organization	Japan Agency for Medical Research and Development
Organization
Division
Category of Funding Organization	Other
Nationality of Funding Organization

Other related organizations
Co-sponsor	Nippon Shinyaku Co., Ltd.
Name of secondary funder(s)

IRB Contact (For public release)
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
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
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）

Other administrative information
Date of disclosure of the study information	2019 Year 11 Month 06 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	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

Progress
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
Other related information

Management information
Registered date	2019 Year 11 Month 06 Day
Last modified on	2022 Year 11 Month 07 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000043651