Background The aim of this study was to evaluate the safety and efficacy of fecal microbiota, live-jslm (RBL; REBYOTA)—the first single-dose, broad consortia microbiota-based live biotherapeutic approved by the US Food and Drug Administration for preventing recurrent Clostridioides difficile infection (rCDI) in adults following standard-of-care (SOC) antibiotic treatment. Methods PUNCH CD3-OLS was a prospective, phase 3, open-label study, conducted across the US and Canada. Participants were aged ≥18 years with documented rCDI and confirmed use of SOC antibiotics. Participants with comorbidities including inflammatory bowel disease and mild-to-moderate immunocompromising conditions could be enrolled. A single dose of RBL was rectally administered within 24–72 hours of antibiotic completion. The primary endpoint was the number of participants with RBL- or administration-related treatment-emergent adverse events (TEAEs). Secondary endpoints included treatment success and sustained clinical response, at 8 weeks and 6 months after RBL administration, respectively. Results Overall, 793 participants were enrolled, of whom 697 received RBL. TEAEs through 8 weeks after administration were reported by 47.3% of participants; most events were mild or moderate gastrointestinal disorders. Serious TEAEs were reported by 3.9% of participants. The treatment success rate at 8 weeks was 73.8%; in participants who achieved treatment success, the sustained clinical response rate at 6 months was 91.0%. Safety and efficacy rates were similar across demographic and baseline characteristic subgroups. Conclusions RBL was safe and efficacious in participants with rCDI and common comorbidities. This is the largest microbiota-based live biotherapeutic study to date, and findings support use of RBL to prevent rCDI in a broad patient population. Clinical Trials Registration NCT03931941.

中文翻译：

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PUNCH CD3-OLS：一项 3 期前瞻性观察队列研究，旨在评估粪便微生物群 Live-jslm （REBYOTA） 在复发性艰难梭菌感染成人中的安全性和有效性


背景 本研究的目的是评估粪便微生物群 live-jslm （RBL;REBYOTA）——美国食品药品监督管理局批准的第一个基于微生物群的单剂量、广泛联盟活体生物治疗药物，用于预防标准护理 （SOC） 抗生素治疗后成人复发性艰难梭菌感染 （rCDI）。方法 PUNCH CD3-OLS 是一项前瞻性 3 期、开放标签研究，在美国和加拿大进行。参与者年龄 ≥18 岁，有记录的 rCDI 并确认使用 SOC 抗生素。患有炎症性肠病和轻度至中度免疫功能低下等合并症的参与者可以入组。在抗生素完成后 24-72 小时内直肠给药单剂量 RBL。主要终点是发生 RBL 或给药相关治疗中出现的不良事件 （TEAE） 的参与者人数。次要终点包括 RBL 给药后 8 周和 6 个月的治疗成功和持续临床反应。结果 共纳入 793 名参与者，其中 697 名接受了 RBL。47.3% 的参与者报告了给药后 8 周的 TEAE;大多数事件是轻度或中度胃肠道疾病。3.9% 的参与者报告了严重的 TEAE。8 周时治疗成功率为 73.8%;在获得治疗成功的参与者中，6 个月时的持续临床反应率为 91.0%。人口统计学和基线特征亚组的安全性和有效率相似。结论 RBL 对 rCDI 和常见合并症的参与者是安全有效的。 这是迄今为止规模最大的基于微生物群的活体生物治疗研究，研究结果支持在广泛的患者群体中使用 RBL 来预防 rCDI。临床试验注册 NCT03931941.