ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety and Dose Finding Study of NS-065/NCNP-01 in Boys With Duchenne Muscular Dystrophy (DMD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02740972
Recruitment Status : Active, not recruiting
First Posted : April 15, 2016
Last Update Posted : December 5, 2017
Sponsor:
Collaborators:
Nippon Shinyaku Co., Ltd.
Cooperative International Neuromuscular Research Group (CINRG)
Therapeutic Research in Neuromuscular Disorders Solutions (TRiNDS)
Information provided by (Responsible Party):
NS Pharma, Inc.

Brief Summary:
The main objective of this study is to evaluate the safety of a high (80mg/kg) and low (40mg/kg) dose of NS-065/NCNP-01 delivered as an intravenous infusion in patients with Duchenne Muscular Dystrophy (DMD) amendable to exon 53 skipping. Additional objectives include tolerability, muscle function and strength, pharmacokinetics and pharmacodynamics.

Condition or disease Intervention/treatment Phase
Duchenne Muscular Dystrophy Drug: NS-065/NCNP-01 Drug: Placebo Phase 2

Detailed Description:

This is a Phase II, multiple center, 2-period, randomized, placebo-controlled, dose finding study of NS-065/NCNP-01 administered by infusion once weekly for 24 weeks to ambulant boys ages 4-<10 years with DMD. Two dose level cohorts will be enrolled. Period 1 of this study will be conducted in a double-blind fashion. Randomized patients will receive weekly IV infusions of NS-065/NCNP-01 or placebo for the first 4 weeks of their participation (Period 1) and NS-065/NCNP-01 by IV infusion for weeks 5-24 (20 weeks of active treatment - Period 2). Analysis of safety data from Period 1 of the 40mg/kg dose cohort will be completed prior to enrolling patients in the 80mg/kg dose cohort.

Patients completing the 24-week study will be eligible for an open-label extension study.

Clinical efficacy will be assessed at regularly scheduled study visits, including functional tests such as the six-minute walk test (6MWT), time to stand (TTSTAND), time to run/walk 10 meters (TTRW), time to climb 4 stairs (TTCLIMB) and quantitative muscle testing (QMT). All patients will undergo a muscle biopsy of the bicep at baseline and a second muscle biopsy at Week 24.

Safety will be assessed through the collection of adverse events (AEs), blood and urine laboratory tests, electrocardiograms (ECGs), vital signs, and physical examinations throughout the study.

Serial blood samples will be taken at four of the study visits to assess the pharmacokinetics of the study drug.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Actual Study Start Date : December 2016
Estimated Primary Completion Date : March 2018
Estimated Study Completion Date : April 2018


Arm Intervention/treatment
Experimental: NS-065/NCNP-01 40mg/kg
Six patients with confirmed DMD with genetic deletions amenable to exon 53 skipping will be administered an intravenous infusion of NS-065/NCNP-01 40mg/kg dose once a week for 24 weeks
Drug: NS-065/NCNP-01
Experimental: NS-065/NCNP-01 80mg/kg
Six patients with confirmed DMD with genetic deletions amenable to exon 53 skipping will be administered an intravenous infusion of NS-065/NCNP-01 80mg/kg once a week for 24 weeks
Drug: NS-065/NCNP-01
Placebo Comparator: Placebo
Two patients in each of the dose groups will be administered placebo as an intravenous infusion once a week for 4 weeks followed by 20 weeks of open label treatment
Drug: Placebo



Primary Outcome Measures :
  1. Incidence of Adverse Events as assessed by CTCAE v4.0. [ Time Frame: 24 weeks of treatment phase ]
  2. Dystrophin protein in muscle as measured by mass spectrometry. [ Time Frame: 20-24 weeks of treatment ]
  3. Drug concentration in plasma. [ Time Frame: 20-24 weeks of treatment ]

Secondary Outcome Measures :
  1. Induction of dystrophin messenger ribonucleic acid (mRNA) in muscle as measured by real time polymerase chain reaction (RT-PCR) for mRNA analysis. [ Time Frame: 20-24 weeks of treatment ]
  2. Induction of dystrophin protein in muscle as measured by western blot and immunofluorescence methods for protein analysis. [ Time Frame: 20-24 weeks of treatment ]
  3. Muscle strength as measured by Quantitative Muscle Testing (QMT). [ Time Frame: 20-24 weeks of treatment ]
  4. Change in distance traveled in the Six-Minute Walk Test (6MWT). [ Time Frame: baseline to 20-24 weeks of treatment ]
  5. Change in Time to Climb 4 Stairs (TTCLIMB). [ Time Frame: baseline to 20-24 weeks of treatment ]
  6. Change in Time to Run/Walk 10 meters (TTRW). [ Time Frame: baseline to 20-24 weeks of treatment ]
  7. Change in Time to Stand (TTSTAND) [ Time Frame: baseline to 20-24 weeks of treatment ]
  8. North Star Ambulatory Assessment (NSAA) results. [ Time Frame: baseline to 20-24 weeks of treatment ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   4 Years to 9 Years   (Child)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male ≥ 4 years and <10 years of age
  • Confirmed DMD mutation(s) in the dystrophin gene that is amenable to skipping of exon 53 to restore the dystrophin mRNA reading frame;
  • Able to walk independently without assistive devices;
  • Ability to complete the time to stand, time to run/walk and time to climb assessments;
  • Stable dose of glucocorticoid for at least 3 months

Exclusion Criteria:

  • Acute illness within 4 weeks prior to the first dose of study medication;
  • Evidence of symptomatic cardiomyopathy. [Note: Asymptomatic cardiac abnormality on investigation would not be exclusionary];
  • Severe allergy or hypersensitivity to medications;
  • Severe behavioral or cognitive problems that preclude participation in the study, in the opinion of the Investigator;
  • Previous or ongoing medical condition, medical history, physical findings or laboratory abnormalities that could affect safety, make it unlikely that treatment and follow-up will be correctly completed or impair the assessment of study results, in the opinion of the Investigator;
  • Patient is taking any other investigational drug currently or within 3 months prior to the start of study treatment; or
  • Patient has had surgery within the 3 months prior to the first anticipated administration of study medication or surgery is planned for anytime during the duration of the study;
  • Patient has previously participated in this study or any other study during which NS-065/NCNP-01 was administered.

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): NCT02740972


Locations
United States, California
UC Davis
Sacramento, California, United States, 95817
United States, Florida
University of Florida Health
Gainesville, Florida, United States
United States, Illinois
Lurie Children's Hospital
Chicago, Illinois, United States
United States, Missouri
Washington University
Saint Louis, Missouri, United States
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States
United States, Virginia
Children's Hospital of Richmond at VCU
Richmond, Virginia, United States
Canada, Alberta
Alberta Children's Hospital
Calgary, Alberta, Canada
Sponsors and Collaborators
NS Pharma, Inc.
Nippon Shinyaku Co., Ltd.
Cooperative International Neuromuscular Research Group (CINRG)
Therapeutic Research in Neuromuscular Disorders Solutions (TRiNDS)
Investigators
Study Chair: Paula R. Clemens, MD University of Pittsburgh

Responsible Party: NS Pharma, Inc.
ClinicalTrials.gov Identifier: NCT02740972     History of Changes
Other Study ID Numbers: NS-065/NCNP-01-201
First Posted: April 15, 2016    Key Record Dates
Last Update Posted: December 5, 2017
Last Verified: December 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

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