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Exploratory Study of NS-065/NCNP-01 in DMD

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ClinicalTrials.gov Identifier: NCT02081625
Recruitment Status : Unknown
Verified November 2014 by National Center of Neurology and Psychiatry, Japan.
Recruitment status was:  Active, not recruiting
First Posted : March 7, 2014
Last Update Posted : November 17, 2014
Sponsor:
Collaborator:
Nippon Shinyaku Co., Ltd.
Information provided by (Responsible Party):
National Center of Neurology and Psychiatry, Japan

Brief Summary:
This study is designed to assess the safety, tolerability, efficacy and pharmacokinetics (PK) of NS-065/NCNP-01 in subjects diagnosed with Duchenne muscular dystrophy (DMD).

Condition or disease Intervention/treatment Phase
Duchenne Muscular Dystrophy Drug: NS-065/NCNP-01 Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Exploratory Study of NS-065/NCNP-01 in Duchenne Muscular Dystrophy
Study Start Date : June 2013
Estimated Primary Completion Date : November 2014
Estimated Study Completion Date : March 2015


Arm Intervention/treatment
Experimental: NS-065/NCNP-01 Drug: NS-065/NCNP-01

NS-065/NCNP-01 for Infusion is packaged as 25 mg/mL in phosphate buffered saline with 1 mL per vial. Study dosages will be infused over a 1 hour period with Normal saline as follows:

Cohort 1: 1.25mg/kg once weekly for 12 weeks; Cohort 2: 5.0mg/kg once weekly for 12 weeks; Cohort 3: 20.0mg/kg once weekly for 12 weeks





Primary Outcome Measures :
  1. Safety and tolerability (adverse event and adverse drug reaction) [ Time Frame: Up to 15-17 weeks (12 weeks treatment period and 3-5 weeks follow up period) ]

Secondary Outcome Measures :
  1. Expression of dystrophin protein [ Time Frame: At 14-15 weeks (2-3 week after from 12 weeks treatment period) ]
  2. Detection of exon53 skipped mRNA of dystrophin [ Time Frame: At 14-15 weeks (2-3 week after from 12 weeks treatment period) ]
  3. NS-065/NCNP-01 concentration of the blood plasma [ Time Frame: 12 weeks ]
  4. NS-065/NCNP-01 concentration of the urine [ Time Frame: 12 weeks ]
  5. Serum Creatine kinase concentration [ Time Frame: 14 weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   5 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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.

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02081625


Locations
Japan
National Center of Neurology and Psychiatry
Kodaira, Tokyo, Japan, 1878551
Sponsors and Collaborators
National Center of Neurology and Psychiatry, Japan
Nippon Shinyaku Co., Ltd.
Investigators
Study Director: Shin'ichi Takeda, MD, PhD National center of Neurology and Psychiatry
Principal Investigator: Hirofumi Komaki, MD, PhD National center of Neurology and Psychiatry

Responsible Party: National Center of Neurology and Psychiatry, Japan
ClinicalTrials.gov Identifier: NCT02081625     History of Changes
Other Study ID Numbers: NCNP/DMT01
UMIN000010964 ( Other Identifier: UMIN-CTR )
First Posted: March 7, 2014    Key Record Dates
Last Update Posted: November 17, 2014
Last Verified: November 2014

Keywords provided by National Center of Neurology and Psychiatry, Japan:
Duchenne muscular dystrophy
NS-065/NCNP-01
exon 53 skipping
morpholino

Additional relevant MeSH terms:
Muscular Dystrophies
Muscular Dystrophy, Duchenne
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked