A Phase 2, Randomized, Placebo-Controlled, Multiple Ascending-Dose Study of ACE-031, a Soluble Activin Receptor Type IIB, in Boys with Duchenne Muscular Dystrophy (DMD) (P04.088)

杜氏肌营养不良 医学 安慰剂 激活素受体 内科学 受体 病理 替代医学
作者
Craig Campbell,Diana M. Escolar,J. Mah,Mark A. Tarnopolsky,Kathryn Selby,H. McMillan,Yang Yao,Dawn Wilson,Rachel Barger,M. A. Sherman,K.M. Attie
出处
期刊:Neurology [Ovid Technologies (Wolters Kluwer)]
卷期号:78 (Meeting Abstracts 1): P04.088-P04.088 被引量:4
标识
DOI:10.1212/wnl.78.1_meetingabstracts.p04.088
摘要

Objective: To evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic (PD) effects of ACE-031 in DMD. Background ACE-031 is a soluble activin type IIB receptor (ActRIIB-IgG1) that binds negative regulators of muscle, including myostatin and activin. In phase 1 studies in healthy adults, ACE-031 treatment resulted in dose-dependent increases in lean mass. Design/Methods: Ambulatory (30ft walk/run Results: Two cohorts completed treatment (C1: 0.5mg/kg SC q4weeks, C2: 1mg/kg SC q2weeks). Mean age was 10.3 years (range 6-17). There were no AEs that were serious, severe, or resulted in discontinuation. Reversible telangiectasias and mild epistaxis were reported in C2. Mean total body lean mass by DXA increased 5.2% in C2 (p=0.015 vs baseline) vs 2.6% in placebo (p=0.20) after 12 weeks. Thigh MRI (C2) showed a trend for decreased muscle volume in placebo group which was attenuated in ACE-031 group. The least-squares mean Δ6MWD was +12meters in combined ACE-031 groups vs -30meters in placebo group after 24 weeks (p=0.06, ANCOVA). The %change in 6MWD correlated with that for 2MWD (r=0.67, p Conclusions: In this phase 2 study of ACE-031 in steroid-treated DMD boys, reversible telangiectasias and mild epistaxis were reported at higher dose. Significant dose-dependent increases in lean mass were observed. There were trends for maintained 6MWD, decreased gain in fat mass, and increased lumbar spine BMD with ACE-031 treatment. Supported by: MDA, PPMD. Disclosure: Dr. Campbell has received research support from Acceleron Pharma and PTC Therapeutics. Dr. Escolar has received personal compensation for activities with Acceleron Pharma as a consultant. Dr. Mah has received research support from Acceleron Pharma Inc. and PTC Therapeutics. Dr. Tarnopolsky has received personal compensation for activities with Genzyme Corporation as a speaker. Dr. Tarnopolsky has received research support from Genzyme Corporation. Dr. Selby has received research support from Acceleron Pharma. Dr. McMillan has nothing to disclose. Dr. Yang has received personal compensation for activities with Acceleron Pharma as an employee. Ms. Wilson has received personal compensation for activities with Acceleron Pharmaceuticals as an employee. Ms. Barger has received personal compensation for activities with Acceleron Pharma as an employee. Dr. Sherman has received personal compensation for activities with Acceleron Pharma as an employee. Dr. Sherman holds stock and/or stock options in Acceleron Pharma. Dr. Attie has received personal compensation for activities with Acceleron Pharma as an employee.

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
小马甲应助vvA11采纳,获得10
刚刚
xu发布了新的文献求助10
刚刚
传奇3应助出门见喜采纳,获得10
刚刚
1秒前
niuhuhu发布了新的文献求助10
1秒前
欢呼洋葱应助1111采纳,获得10
1秒前
1秒前
2秒前
4秒前
5秒前
搜集达人应助孙大圣采纳,获得10
5秒前
David应助自然的南露采纳,获得10
6秒前
6秒前
落寞的妖妖完成签到,获得积分10
7秒前
7秒前
豆豆完成签到,获得积分10
8秒前
YanXuanhua完成签到,获得积分10
8秒前
lhr完成签到,获得积分10
8秒前
万能图书馆应助遇见采纳,获得10
9秒前
9秒前
Zoey626应助luckss采纳,获得10
9秒前
10秒前
11秒前
pcyang完成签到,获得积分10
13秒前
以水为师发布了新的文献求助10
13秒前
Owen应助科研通管家采纳,获得10
13秒前
NexusExplorer应助科研通管家采纳,获得10
13秒前
桐桐应助科研通管家采纳,获得10
13秒前
爆米花应助科研通管家采纳,获得10
13秒前
领导范儿应助科研通管家采纳,获得10
13秒前
13秒前
13秒前
李爱国应助科研通管家采纳,获得30
13秒前
不安青牛应助科研通管家采纳,获得10
14秒前
CipherSage应助科研通管家采纳,获得10
14秒前
欢呼洋葱应助酷炫的靖仇采纳,获得10
14秒前
领导范儿应助科研通管家采纳,获得30
14秒前
小二郎应助科研通管家采纳,获得10
14秒前
Singularity应助科研通管家采纳,获得10
14秒前
吴宣京完成签到,获得积分10
14秒前
高分求助中
Востребованный временем 2500
Agaricales of New Zealand 1: Pluteaceae - Entolomataceae 1040
Healthcare Finance: Modern Financial Analysis for Accelerating Biomedical Innovation 1000
지식생태학: 생태학, 죽은 지식을 깨우다 600
海南省蛇咬伤流行病学特征与预后影响因素分析 500
Neuromuscular and Electrodiagnostic Medicine Board Review 500
ランス多機能化技術による溶鋼脱ガス処理の高効率化の研究 500
热门求助领域 (近24小时)
化学 医学 材料科学 生物 工程类 有机化学 生物化学 纳米技术 内科学 物理 化学工程 计算机科学 复合材料 基因 遗传学 物理化学 催化作用 细胞生物学 免疫学 电极
热门帖子
关注 科研通微信公众号,转发送积分 3463229
求助须知:如何正确求助?哪些是违规求助? 3056638
关于积分的说明 9053048
捐赠科研通 2746497
什么是DOI,文献DOI怎么找? 1506946
科研通“疑难数据库(出版商)”最低求助积分说明 696243
邀请新用户注册赠送积分活动 695849