Complement C3 activation contributes to COVID-19 pathology, and C3 targeting has emerged as a promising therapeutic strategy. We provide interim data from ITHACA, the first randomized trial evaluating a C3 inhibitor, AMY-101, in severe COVID-19 (PaO2/FiO2 ≤ 300 mmHg). Patients received AMY-101 ( n = 16) or placebo ( n = 15) in addition to standard of care. AMY-101 was safe and well tolerated. Compared to placebo (8 of 15, 53.3%), a higher, albeit nonsignificant, proportion of AMY-101–treated patients (13 of 16, 81.3%) were free of supplemental oxygen at day 14. Three nonresponders and two placebo-treated patients succumbed to disease-related complications. AMY-101 significantly reduced CRP and ferritin and restrained thrombin and NET generation. Complete and sustained C3 inhibition was observed in all responders. Residual C3 activity in the three nonresponders suggested the presence of a convertase-independent C3 activation pathway overriding the drug’s inhibitory activity. These findings support the design of larger trials exploring the potential of C3-based inhibition in COVID-19 or other complement-mediated diseases.

中文翻译：

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使用坎普他汀 AMY-101 在严重 COVID-19 中补充 C3 抑制

补体 C3 激活有助于 COVID-19 病理学，C3 靶向已成为一种有前途的治疗策略。我们提供来自 ITHACA 的中期数据，这是第一个评估 C3 抑制剂 AMY-101 在严重 COVID-19（PaO2/FiO2 ≤ 300 mmHg）中的随机试验。患者接受了 AMY-101（n= 16) 或安慰剂 (n= 15) 除了护理标准。AMY-101 是安全且耐受性良好的。与安慰剂相比（15 人中有 8 人，53.3%），接受 AMY-101 治疗的患者中有更高比例（16 人中有 13 人，81.3%）在第 14 天没有补充氧气。三名无反应者和两名接受安慰剂治疗的患者患者死于与疾病相关的并发症。AMY-101 显着降低 CRP 和铁蛋白，并抑制凝血酶和 NET 的产生。在所有反应者中观察到完全和持续的 C3 抑制。三名无反应者中残留的 C3 活性表明存在一种不依赖于转化酶的 C3 激活途径，该途径超越了药物的抑制活性。这些发现支持设计更大规模的试验，探索基于 C3 的抑制作用在 COVID-19 或其他补体介导的疾病中的潜力。