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

NCT02740972 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: NS-065/NCNP-01-201
• Study Type: interventional
• Target: 16
• Locations: 2 countries
• Sites: 7

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.

Conditions

Duchenne Muscular Dystrophy

Outcome Measures

Primary Outcomes (2)

• Incidence of Adverse Events as Assessed by CTCAE v4.0.

  Treatment emergent adverse events (TEAEs) were summarized for Period 1 by comparing low dose to high dose to placebo and for Period 2 between the low dose cohort and the high dose cohort. TEAEs were summarized both at the patient level for number of TEAEs, highest severity, relationship, action and outcome and at the TEAE level (summarizing events) by organ system and preferred term TEAE as well as severity, relationship, action and outcome. The Medical Dictionary for Regulatory Activities (MedDRA) version 20.1 was used and the Common Terminology Criteria for Adverse Events (CTCAE) grading.

  24 weeks of treatment

• Dystrophin Production by Western Blot

  Percentage normal dystrophin production in muscle biopsies from study participants at baseline and after 24 weeks treatment was measured by Western blot. To analyze dystrophin induction, biopsies were taken from a biceps muscle at baseline and the other biceps muscle after 24 weeks of treatment. Muscle samples were snap frozen and delivered to a central laboratory. All laboratory researchers remained blinded to sample identity. Dystrophin protein levels were assessed using standard curves on each gel (range from 0-25% of normal levels) generated by mixing 5 normal control samples with one DMD sample.

  Baseline and 24 weeks of treatment

Secondary Outcomes (12)

• Dystrophin Production by RT-PCR for mRNA - Percentage of Exons Skipped - Molarity

  Baseline and 24 weeks of treatment

• Dystrophin Production by Mass Spectrometry

  Baseline and 24 weeks of treatment

• Dystrophin Production by Immunofluorescence

  Baseline and 24 weeks of treatment

• Change From Baseline in Muscle Strength as Measured by Quantitative Muscle Testing (QMT).

  Baseline and 24 weeks of treatment

• Change From Baseline in Distance Traveled in the Six-Minute Walk Test (6MWT).

  Baseline and 24 weeks of treatment

Study Arms (3)

NS-065/NCNP-01 40mg/kg

EXPERIMENTAL

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

NS-065/NCNP-01 80mg/kg

EXPERIMENTAL

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

PLACEBO COMPARATOR

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

Interventions

NS-065/NCNP-01 DRUG

NS-065/NCNP-01 40mg/kg; NS-065/NCNP-01 80mg/kg

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 4 Years - 9 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• Acute illness within 4 weeks prior to the first dose of study medication;
• 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.

Sponsors & Collaborators

• NS Pharma, Inc.: lead
• Nippon Shinyaku Co., Ltd.: collaborator
• Cooperative International Neuromuscular Research Group: collaborator
• Therapeutic Research in Neuromuscular Disorders Solutions: collaborator

Study Sites (7)

UC Davis

Sacramento, California, 95817, United States

Location

University of Florida Health

Gainesville, Florida, United States

Location

Lurie Children's Hospital

Chicago, Illinois, United States

Location

Washington University

St Louis, Missouri, United States

Location

Duke University Medical Center

Durham, North Carolina, United States

Location

Children's Hospital of Richmond at VCU

Richmond, Virginia, United States

Location

Alberta Children's Hospital

Calgary, Alberta, Canada

Location

Related Publications (1)

• Clemens PR, Rao VK, Connolly AM, Harper AD, Mah JK, Smith EC, McDonald CM, Zaidman CM, Morgenroth LP, Osaki H, Satou Y, Yamashita T, Hoffman EP; CINRG DNHS Investigators. Safety, Tolerability, and Efficacy of Viltolarsen in Boys With Duchenne Muscular Dystrophy Amenable to Exon 53 Skipping: A Phase 2 Randomized Clinical Trial. JAMA Neurol. 2020 Aug 1;77(8):982-991. doi: 10.1001/jamaneurol.2020.1264.

  PMID: 32453377 DERIVED

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Medical Affairs
• Organization: NS Pharma, Inc.

trialinfo@nspharma.com

(201) 986-3860

Study Officials

• Paula R. Clemens, MD

  University of Pittsburgh

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2016
• First Posted: April 15, 2016
• Study Start: December 1, 2016
• Primary Completion: March 1, 2018
• Study Completion: April 1, 2018
• Last Updated: December 7, 2021
• Results First Posted: July 12, 2021

Record last verified: 2021-11

Locations

CA (1); US (6)