CP101的安全性和耐受性，一种用于预防艰难梭菌反复感染的全谱口服微生物组疗法：一项2期随机对照试验。
Safety and Tolerability of CP101, a Full-Spectrum, Oral Microbiome Therapeutic for the Prevention of Recurrent Clostridioides difficile Infection: A Phase 2 Randomized Controlled Trial.
作者信息
Allegretti Jessica R, Kelly Colleen R, Louie Thomas, Fischer Monika, Hota Susy, Misra Bharat, Van Hise Nick W, Yen Eugene, Bullock Jeffrey S, Silverman Michael, Davis Ian, McGill Sarah K, Pardi Darrell S, Orenstein Robert, Grinspan Ari, El-Nachef Najwa, Feuerstadt Paul, Borody Thomas J, Khanna Sahil, Budree Shrish, Kassam Zain
机构信息
Division of Gastroenterology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Division of Gastroenterology, Warren Alpert Medical School of Brown University, Providence, Rhode Island.
出版信息
Gastroenterology. 2025 Feb;168(2):357-366.e3. doi: 10.1053/j.gastro.2024.09.030. Epub 2024 Oct 2.
BACKGROUND & AIMS: Recurrent Clostridioides difficile infections (CDIs) remain common. While novel microbiome therapeutics gain approval, the efficacy of a full-spectrum, oral microbiome therapeutic is unknown. This study aimed to determine the safety and efficacy of CP101, an orally administered microbiome therapeutic, to restore a diverse microbiome and prevent recurrent CDI in a broad population.
METHODS
We conducted a multicenter, phase 2, double-blind, randomized, placebo-controlled trial in adults with recurrent CDI. Participants with one or more CDI recurrences and diagnosis by polymerase chain reaction or toxin enzyme immunoassay for the qualifying episode were included. Participants were randomized 1:1 to receive a single oral dose of either CP101 (∼6 × 10 colony-forming units of lyophilized microbial cells) or placebo after standard-of-care antibiotics. The primary efficacy endpoint was the proportion of participants without CDI recurrence through week 8. Safety, efficacy, and microbiome endpoints were evaluated through weeks 8 and 24.
RESULTS
A total of 198 participants were analyzed: CP101 (n = 102) and placebo (n = 96). Overall, 27.5% had a first recurrence, and 62.7% were diagnosed by polymerase chain reaction-based testing. The proportion without CDI recurrence through week 8 was significantly higher in the CP101 group compared to the placebo group (74.5% [76 of 102] vs 61.5% [59 of 96], respectively; P = .0488), with durable efficacy observed through week 24 (73.5% [75 of 102] vs 59.4% [57 of 96], respectively; P = .0347). Similar efficacy was observed regardless of diagnostic modality or number of CDI recurrences. Rapid and durable increase in microbiome diversity was observed in the CP101 group compared to the placebo group. The incidence of adverse events was similar between the 2 groups.
CONCLUSIONS
CP101 was superior to placebo in reducing recurrent CDI with a safety profile similar to placebo. (ClinicalTrials.gov, Number NCT03110133).
背景与目的
艰难梭菌感染（CDI）复发仍然很常见。虽然新型微生物组疗法已获批准，但全谱口服微生物组疗法的疗效尚不清楚。本研究旨在确定口服微生物组疗法CP101在广泛人群中恢复多样化微生物组并预防CDI复发的安全性和疗效。
方法
我们对复发性CDI成人患者进行了一项多中心、2期、双盲、随机、安慰剂对照试验。纳入有一次或多次CDI复发且通过聚合酶链反应或毒素酶免疫测定法对合格发作进行诊断的参与者。参与者按1:1随机分组，在接受标准护理抗生素治疗后，单次口服CP101（约6×10个冻干微生物细胞集落形成单位）或安慰剂。主要疗效终点是至第8周无CDI复发的参与者比例。通过第8周和第24周评估安全性、疗效和微生物组终点。
结果
共分析了198名参与者：CP101组（n = 102）和安慰剂组（n = 96）。总体而言，27.5%的人有首次复发，62.7%通过基于聚合酶链反应的检测确诊。与安慰剂组相比，CP101组至第8周无CDI复发的比例显著更高（分别为74.5%[102例中的76例]和61.5%[96例中的59例]；P = 0.0488），至第24周观察到持久疗效（分别为73.5%[102例中的75例]和59.4%[96例中的57例]；P = 0.0347）。无论诊断方式或CDI复发次数如何，均观察到相似的疗效。与安慰剂组相比，CP101组微生物组多样性迅速且持久增加。两组不良事件发生率相似。
结论
CP101在降低CDI复发方面优于安慰剂，安全性与安慰剂相似。（ClinicalTrials.gov，编号NCT03110133）
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