Phase II Study of NPC-14 (Arbekacin Sulfate) to Explore Safety, Tolerability, and Efficacy in Duchenne Muscular Dystrophy

Summary

Duchenne Muscular Dystrophy (DMD) is inherited neuromuscular disorders due to mutation in the gene that encodes critical muscle protein called dystrophin. Currently, there is no effective treatment option for the disease. A pharmacological approach by promoting mRNA translation regardless of the presence of premature stop codons by nonsense mutation, called the readthrough strategy, has been developing recently for DMD with nonsense mutation. NPC-14 is a candidate compound for the readthrough strategy, since effective readthrough activities were demonstrated in nonclinical studies. This study is a phase II study designed to assess safety, tolerability, and efficacy of NPC-14 in ambulant DMD patients with nonsense mutation that were confirmed by whole genome analysis. These goals will be accomplished by monitoring adverse events by physical examination, cardiac, pulmonary, auditory, balance, and laboratory tests as safety endpoints, and dystrophin expression in muscle biopsy as primary efficacy endpoint, muscle function (NSAA, timed test, muscle strength (QMT, MMT) , dairy activities by lifecorder), and biomarkers as secondary efficacy endpoints. The study is a randomized, double blind, placebo-controlled study in 21 DMD patients. After screening, eligible patients are allocated dynamically to weekly NPC-14 or a placebo (saline) in a 2:1 ratio and will receive study drugs for 36 weeks.

Conditions

• Muscular Dystrophy, Duchenne

Interventions

DRUG

NPC-14

NPC-14 will be administrated as following steps. The dose of NPC-14 will be calculated and adjusted by a non-blinded medical doctor and/or a non-blinded pharmacist. * An initial dose of NPC-14 will be half of that calculated by distribution volume：Vd based on patient age for safety reason. * After the initial administration, the dose of NPC-14 will be adjusted and maintained by actual Vd, therapeutic drug monitoring of peak serum levels of NPC-14

DRUG

Placebo

Dose will be adjusted by volume of distribution (Vd) of patients in accordance with the NPC-14 dose regimen

Sponsors & Collaborators

• Japan Medical Association

  collaborator INDUSTRY

• Nobelpharma

  collaborator INDUSTRY

• Kobe University

  lead INDUSTRY

Principal Investigators

• Yasuhiro Takeshima, MD, PhD · Hyogo Medical University

• Hirofumi Komaki, MD, PhD · National center of neurology and psychiatry, department of child neurology, Muscular disease center

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

4 Years

Sex

MALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2013-08-31

Primary Completion

2015-10-31

Completion

2015-10-31

Countries

• Japan

Study Locations