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

NCT ID: NCT02740972

Last Updated: 2021-12-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-31
• Study Completion Date: 2018-04-30

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.

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.

Conditions

Duchenne Muscular Dystrophy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: EXPERIMENTAL

NS-065/NCNP-01

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

NS-065/NCNP-01

Intervention Type: DRUG

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

NS-065/NCNP-01

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 4 Years
• Maximum Eligible Age: 9 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Nippon Shinyaku Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Cooperative International Neuromuscular Research Group

NETWORK

Sponsor Role: collaborator

Therapeutic Research in Neuromuscular Disorders Solutions

INDUSTRY

Sponsor Role: collaborator

NS Pharma, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paula R. Clemens, MD

Role: STUDY_CHAIR

University of Pittsburgh

Locations

UC Davis

Sacramento, California, United States

University of Florida Health

Gainesville, Florida, United States

Lurie Children's Hospital

Chicago, Illinois, United States

Washington University

St Louis, Missouri, United States

Duke University Medical Center

Durham, North Carolina, United States

Children's Hospital of Richmond at VCU

Richmond, Virginia, United States

Alberta Children's Hospital

Calgary, Alberta, Canada

Countries

United States; Canada

References

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.

Reference Type: DERIVED

PMID: 32453377 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NS-065/NCNP-01-201

Identifier Type: -

Identifier Source: org_study_id