Pilot study of RTB101 as COVID-19 prophylaxis in older adults with amended research plan and budget

摘要 鉴于新冠肺炎感染在老年人中的高死亡率(Wu等人，2020年)， 迫切需要评估可以预防这些脆弱人群严重疾病的药物 病人。对雷帕霉素复合体1靶基因下游靶点的抑制作用 据报道，上调泛抗病毒基因表达并保护小鼠免受病毒呼吸道感染 肠道感染(RTI)(York AG等人)2015年)。重要的是，RTB101也被观察到 上调干扰素刺激的泛抗病毒基因表达，降低 血清中炎性细胞因子，降低病毒性呼吸道感染的发生率和严重程度 冬季寒冷期间预防性服用包括冠状病毒感染在内的呼吸道感染 和流感季节向老年人传播(Mannick等人。2018年，曼尼克等人，2019年)。因此我们 假设当给予RTB101时，将降低新冠肺炎的发生率和严重程度 对老年人的预防。在对这一适应症进行大规模、强有力的试验之前，我们 提议进行一项试点研究，以确定招募、同意、 对被隔离的老年人群进行筛查和随机化 为增加发展新冠肺炎的风险(具体目标1)，评估新冠肺炎是否 可以使用电子日记跟踪老年人的症状(特定目标2)，并获得 应用RT_(101)AS治疗的受试者新冠肺炎发生率和严重程度的初步数据 与安慰剂(特定目标3)相比。试验中产生的数据将用于帮助 优化更大且动力充足的研究的研究设计以确定RTB101是否 在老年人中，新冠肺炎预防有效。

Abstract Given the elevated mortality of COVID-19 infections in older adults (Wu et al 2020), there is an urgent need to evaluate medicines that may prevent severe disease in these vulnerable patients. Inhibition of targets downstream of target of rapamycin complex 1 (TORC1) was reported to upregulate pan-antiviral gene expression and protect mice from a viral respiratory tract infection (RTI) (York AG et al. 2015). Importantly, RTB101 was also observed to upregulate interferon-stimulated pan-antiviral gene expression, decrease the levels of inflammatory cytokines in serum, and decrease the incidence and severity of viral respiratory tract infections including coronavirus infections when given as prophylaxis during winter cold and flu season to older adults (Mannick et al. 2018, Mannick et al., 2019). Therefore we hypothesize that RTB101 will decrease the incidence and severity of COVID-19 when given as prophylaxis to older adults. Before undertaking a large well-powered trial for this indication, we propose to undertake a pilot study to determine the feasibility of recruiting, consenting, screening and randomizing quarantined outpatient populations of older adults who are predicted to be at increased risk of developing COVID-19 (Specific Aim 1), assess whether COVID-19 symptoms can be tracked using an eDiary in older adults (Specific Aim 2), and obtain preliminary data on the incidence and severity of COVID-19 in subjects treated with RTB101 as compared to placebo (Specific Aim 3). The data generated in the trial will be used to help optimize the study design of a larger adequately powered study to determine if RTB101 is effective as COVID-19 prophylaxis in the older adults.