Source: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000043651
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Unique ID issued by UMIN UMIN000038505
Receipt No. R000043651
Scientific Title Exploratory Study of NS-089/NCNP-02 in Duchenne muscular dystrophy
Date of disclosure of the study information 2019/11/06
Last modified on 2019/11/06
Public title Exploratory Study of NS-089/NCNP-02 in Duchenne muscular dystrophy
Acronym Exploratory Study of NS-089/NCNP-02
Scientific Title:Acronym Exploratory Study of NS-089/NCNP-02
Condition Duchenne muscular dystrophy
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.
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
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."
4 years-old <=
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
1st name Hirofumi
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
Email komakih@ncnp.go.jp
1st name Yasuko
Last name Asahina
Division name Clinical Research Suppor Office, Translaional Medical Center
Email tmc-crso@ncnp.go.jp
Institute National Center of Neurology and Psychiatry
Co-sponsor Nippon Shinyaku Co., Ltd.
Organization IRB, National Center of Neurology and Psychiatry
Email irb-office@ncnp.go.jp
Study ID_1 NCT04129294
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）
2019 Year 11 Month 06 Day
2019 Year 10 Month 04 Day
URL(English) https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000043651