BIO101 in Sarcopenic Seniors at Risk of Mobility Disability: Results of a Double-Blind Randomised Interventional Phase 2b Trial

IF 9.4 1区医学 Q1 GERIATRICS & GERONTOLOGY

Journal of Cachexia Sarcopenia and Muscle Pub Date : 2025-03-03 DOI:10.1002/jcsm.13750

Roger A. Fielding, Michael M. Dao, Kevin Cannon, Moise Desvarieux, Sam S. Miller, Michael Paul Gimness, Donald M. Brandon, Dennis T. Villareal, Olivier Bruyere, Ivan Bautmans, Kyle Rickner, Robert Perry, Stephen B. Kritchevsky, Nicolas Musi, Joe M. Chehade, Judith L. Kirstein, Evelien Gielen, Paul Pickrell, Pierre Dilda, Rene Lafont, Carole Margalef, Yves Rolland, Susanna Del Signore, Jean Mariani, Samuel Agus, Cendrine Tourette, Waly Dioh, Rob van Maanen, Stanislas Veillet

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Abstract

Background

Sarcopenia is a progressive muscle disorder that may lead to mobility disability. No pharmaceutical interventions are currently available, and treatment relies on physical exercise and nutrition. The aim of SARA-INT was to investigate whether BIO101 (20-hydroxyecdysone), an activator of the MAS receptor, is safe and improves muscle function and physical performance of community dwelling older sarcopenic patients.

Methods

SARA-INT was a randomised three-arm interventional study (BIO101 175 mg bid /350 mg bid/placebo) with a planned 6-month treatment (up to 9 months in 50 subjects). Eligibility criteria for sarcopenia were meeting FNIH criteria for sarcopenia and Short Physical Performance Battery (SPPB) score ≤ 8/12 in men and women aged ≥ 65 years. Primary endpoint was the change from baseline (CFB) in gait speed (GS) measured by 400-m walking test (400MWT), secondary endpoints being CFB in other physical performance tests.

Results

A total of 233 participants were randomised (mean age 75.5 ± 7.12; 54.3% female), of whom 232 and 156 were included in the full analysis set (FAS) and per-protocol (PP) populations, respectively. Due to COVID-19 pandemic, 55% of on-site end-of-treatment efficacy assessments were lost, reducing the studies' power. In the primary analysis (mix of 6/9 months), BIO101 350 mg bid treatment after 6/9 months was associated with an improvement in the 400MWT of 0.07 m/s versus placebo in the FAS population (not significant) and of 0.09 m/s in the PP population (p = 0.008). BIO101 350 mg bid treatment effect on the 400MWT GS was also observed in pre-defined subpopulations at higher risk of mobility disability (0.0474 m/s for slow walkers, 0.0521 m/s for obese and 0.0662 m/s for chair stand sub-score ≤ 2 from SPPB in the FAS population), with a trend for a dose response. BIO101 showed a good safety profile at both doses (number of subjects with related treatment emergent adverse events (TEAEs) of 13 (16.0%), 10 (13.3%) and 10 (13.5%) in the placebo, 175 mg and 350 mg BIO101 groups, respectively).

Conclusions

After 6 to 9 months of treatment, BIO101 350 mg bid showed strong trends consistent with a clinically relevant effect on the 400MWT GS, close to the minimal clinically important difference (MCID) in sarcopenia (0.1 m/s). This was also shown in predefined subpopulations at higher risk of mobility disability. BIO101 showed a good safety profile. Taken together, efficacy and safety data of this Phase 2 trial encourage us to pursue further development of BIO101 for the treatment of sarcopenia.

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BIO101治疗有行动障碍风险的老年肌肉减少症患者：一项双盲随机介入2b期试验的结果

背景：肌肉减少症是一种进行性肌肉疾病，可导致活动障碍。目前没有药物干预措施，治疗依赖于体育锻炼和营养。SARA-INT的目的是研究MAS受体激活剂BIO101（20-羟基蜕皮激素）是否安全，并改善社区老年肌肉减少症患者的肌肉功能和身体表现。SARA-INT是一项随机三组介入研究（BIO101 175 mg bid/ 350 mg bid/安慰剂），计划治疗6个月（50名受试者长达9个月）。骨骼肌减少症的诊断标准为：年龄≥65岁的男性和女性符合FNIH骨骼肌减少症和短体能性能电池（SPPB）评分≤8/12的标准。主要终点是通过400米步行测试（400MWT）测量的步态速度（GS）与基线的变化（CFB），次要终点是其他物理性能测试中的CFB。结果共纳入233例受试者(平均年龄75.5±7.12；54.3%女性)，其中232和156人分别被纳入完整分析集（FAS）和按方案（PP）群体。由于COVID-19大流行，55%的现场治疗结束疗效评估丢失，降低了研究的有效性。在初步分析（6/9个月的混合）中，6/9个月后BIO101 350 mg bid治疗与FAS人群（无显著性）和PP人群（0.09 m/s）的400MWT改善相关（p = 0.008），分别为0.07 m/s和0.09 m/s。BIO101 350 mg bid对400MWT GS的治疗效果也在预定义的行动障碍高风险亚群中观察到（慢行者0.0474 m/s，肥胖者0.0521 m/s， FAS人群SPPB评分≤2的椅子站立亚群0.0662 m/s），并有剂量反应的趋势。BIO101在两种剂量下均显示出良好的安全性（在安慰剂、175 mg和350 mg BIO101组中，出现相关治疗紧急不良事件（teae）的受试者人数分别为13人（16.0%）、10人（13.3%）和10人（13.5%））。结论治疗6 ~ 9个月后，BIO101 350mg bid对400MWT GS的影响趋势与临床相关效果一致，接近肌肉减少症的最小临床重要差异（MCID）（0.1 m/s）。这在行动障碍风险较高的预定义亚群中也有所体现。BIO101显示出良好的安全性。综上所述，该2期试验的有效性和安全性数据鼓励我们进一步开发BIO101治疗肌肉减少症。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Cachexia Sarcopenia and Muscle MEDICINE, GENERAL & INTERNAL-

CiteScore

13.30

自引率

12.40%

发文量

234

审稿时长

16 weeks

期刊介绍： The Journal of Cachexia, Sarcopenia and Muscle is a peer-reviewed international journal dedicated to publishing materials related to cachexia and sarcopenia, as well as body composition and its physiological and pathophysiological changes across the lifespan and in response to various illnesses from all fields of life sciences. The journal aims to provide a reliable resource for professionals interested in related research or involved in the clinical care of affected patients, such as those suffering from AIDS, cancer, chronic heart failure, chronic lung disease, liver cirrhosis, chronic kidney failure, rheumatoid arthritis, or sepsis.