Clinical Study to Assess the Safety fo AVI-4658 in Subjects With Duchenne Muscular Dystrophy Due to a Frame-shift Mutation Amenable to Correction by Skipping Exon 51.

Sarepta Therapeutics, Inc.2 个研究点分布在 1 个国家目标入组 19 人开始时间: 2009年1月最近更新: 2015年10月6日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Sarepta Therapeutics, Inc.
入组人数: 19
试验地点: 2
主要终点: Treatment Emergent Adverse Events

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The specific aim of this Phase I/II study is to assess the safety of intravenous administered Morpholino oligomer directed against exon 51 (AVI-4658 PMO).

详细描述

Primary outcome is safety, tolerability and dose selection for future studies.

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Single Group
主要目的: Treatment
盲法: None

入排标准

年龄范围: 5 Years 至 15 Years（Child）
性别: Male
接受健康志愿者: 否

入选标准

•Has provided written informed assent (as required by EC) and parents/guardians have provided written informed consent.
•Has an out-of-frame deletion(s) that could be corrected by skipping exon 51 based on DNA sequencing data from the candidate.
•Is male and between the ages of ≥ 5 years and ≤ 15 years.
•Has a muscle biopsy analysis showing < 5% revertant fibres present at baseline.
•DNA sequencing of the candidate's dystrophin exon 51 confirms that no DNA polymorphisms are present that could compromise PMO duplex formation or there is confirmation of in vitro dystrophin production after AVI-4658 exposure to fibroblast or myoblast in vitro cultures.
•Intact right and left bicep muscles or alternative arm muscle group.
•Is able to walk independently at least 25 meters.
•Has a forced vital capacity (FVC) ≥ 50% of predicted and does not require ventilatory support or supplemental oxygen.
•Receives the standard of care for DMD as recommended by the DMD care recommendations from the North Star UK and TREAT-NMD.
•The parent(s) or legal guardian and Subject have undergone counselling about the expectations of this protocol and agree to participate.
•The parent(s) or legal guardian and Subject intend to comply with all study evaluations and return for all study activities.

排除标准

•A DNA polymorphism within exon 51 that may compromise PMO duplex formation.
•Known antibodies to dystrophin.
•Lacks intact right and left bicep muscles or alternative arm muscle group.
•A calculated creatinine clearance less than 70% of predicted normal for age based on the Cockcroft and Gault Formula.
•A left ventricular ejection fraction (EF) of < 35% and/or fractional shortening of <25% based on echocardiography (ECHO)during screening.
•A history of respiratory insufficiency as defined by need for intermittent or continuous supplemental oxygen.
•A severe cognitive dysfunction rendering the potential subject unable to understand and comply with the study protocol.
•Any known immune deficiency or autoimmune disease.
•A known bleeding disorder or has received chronic anticoagulant treatment within three months of study entry.
•Receipt of pharmacologic treatment, apart from corticosteroids, that might affect muscle strength or function within 8 weeks of study entry (viz., growth hormone, anabolic steroids).
•Surgery within 3 months of study entry or planned for anytime during the duration of the study.
•Another clinically significant illness at time of study entry.
•Subject or parent has active psychiatric disorder, has adverse psychosocial circumstances,recent significant emotional loss, and/or history of depressive or anxiety disorder that might interfere with protocol compliance.
•Use of any experimental treatments, has participated in any DMD interventional clinical trial within 4 weeks of study entry or participated in the AVI-4658-33 intramuscular (i.m.) trial.

研究组 & 干预措施

Cohort 1 - 0.5 mg/kg/wk

Experimental

Subjects in this group will receive a 0.5 mg/kg/wk dose of AVI-4658 over 12 weekly IV infusions in 50 mL of normal saline solution over a 60-minute period