Feuerstadt Paul, Chopra Teena, Knapple Whitfield, Van Hise Nicholas W, Dubberke Erik R, Baggott Brian, Guthmueller Beth, Bancke Lindy, Gamborg Michael, Steiner Theodore S, Van Handel Daniel, Khanna Sahil
Digestive Diseases, Yale School of Medicine, New Haven, Connecticut, USA.
Division of Infectious Diseases, Wayne State University, Detroit, Michigan, USA.
Clin Infect Dis. 2025 Feb 5;80(1):43-51. doi: 10.1093/cid/ciae437.
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.
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.
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.
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.
NCT03931941.
本研究旨在评估粪便微生物群制剂——活菌-jslm（RBL；商品名REBYOTA）的安全性和有效性。RBL是美国食品药品监督管理局批准的首个单剂量、基于广泛菌群的活菌生物疗法，用于预防接受标准治疗（SOC）抗生素治疗的成人复发性艰难梭菌感染（rCDI）。
PUNCH CD3 - OLS是一项在美国和加拿大开展的前瞻性3期开放标签研究。参与者年龄≥18岁，有记录的rCDI且确认使用了SOC抗生素。患有包括炎症性肠病和轻度至中度免疫功能低下疾病等合并症 的参与者也可入组。在抗生素治疗结束后24 - 72小时内，经直肠给予单剂量RBL。主要终点是发生与RBL或给药相关的治疗中出现的不良事件（TEAE）的参与者数量。次要终点分别为RBL给药后8周和6个月时的治疗成功率和持续临床反应。
总体而言，793名参与者入组，其中697名接受了RBL治疗。47.3%的参与者报告了给药后8周内的TEAE；大多数事件为轻度或中度胃肠道疾病。3.9%的参与者报告了严重TEAE。8周时的治疗成功率为73.8%；在实现治疗成功的参与者中，6个月时的持续临床反应率为91.0%。不同人口统计学和基线特征亚组的安全性和有效性率相似。
RBL对患有rCDI和常见合并症的参与者安全有效。这是迄今为止规模最大的基于微生物群的活菌生物疗法研究，研究结果支持在广泛的患者群体中使用RBL预防rCDI。
NCT03931941
