Safety and Tolerability of CP101, a full spectrum, oral microbiome therapeutic for the prevention of recurrent C. difficile infection: A Phase 2 Randomized Controlled Trial.

IF 25.7 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gastroenterology Pub Date : 2024-10-02 DOI:10.1053/j.gastro.2024.09.030

Jessica R. Allegretti, Colleen R. Kelly, Thomas Louie, Monika Fischer, Susy Hota, Bharat Misra, Nick W. Van Hise, Eugene Yen, Jeffrey S. Bullock, Michael Silverman, Ian Davis, Sarah K. McGill, Darrell S. Pardi, Robert Orenstein, Ari Grinspan, Najwa El-Nachef, Paul Feuerstadt, Thomas J. Borody, Sahil Khanna S, Shrish Budree, Zain Kassam

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引用次数: 0

Abstract

Background and Aims

Recurrent Clostridioides difficile infections (CDI) remain common. While novel microbiome therapeutics gain approval, the efficacy of a full spectrum, oral microbiome therapeutics 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 multi-center, phase 2, double-blind, randomized, placebo-controlled trial in adults with recurrent CDI. Participants with one or more CDI recurrences and diagnosis by PCR or toxin EIA for the qualifying episode were included. Participants were randomized 1:1 to receive a single oral dose of either CP101 (∼ 6 x 10¹¹ CFU of lyophilized microbial cells) or placebo after standard-of-care (SOC) antibiotics. The primary efficacy endpoint was the proportion of participants without CDI recurrence through Week 8. Safety, efficacy and microbiome endpoints were evaluated through Week 8 and 24.

Results

198 participants were analyzed; CP101 (n=102) and placebo (n=96). Overall, 27.5% with a first recurrence and 62.7% diagnosed by PCR-based testing. The proportion without CDI recurrence through Week 8 was significantly higher in the CP101 group compared to placebo (74.5% [76/102] vs 61.5% [59/96], p=0.0488) with durable efficacy observed through Week 24 (73.5% [75/102] vs 59.4% [57/96], p=0.0347). 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 placebo. The incidence of adverse events was similar between the two groups.

Conclusions

CP101 was superior to placebo in reducing recurrent CDI with a safety profile similar to placebo. https://clinicaltrials.gov/study/NCT03110133

查看原文本刊更多论文

用于预防艰难梭菌复发感染的全方位口服微生物组疗法 CP101 的安全性和耐受性：2期随机对照试验。

背景和目的复发性艰难梭菌感染（CDI）仍然很常见。虽然新型微生物组疗法已获得批准，但全方位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 的安全性和疗效，以在广泛人群中恢复多样化的微生物组并预防复发性 CDI。方法我们在复发性 CDI 成人患者中开展了一项多中心、2 期、双盲、随机、安慰剂对照试验。试验对象包括复发过一次或多次 CDI 并经 PCR 或毒素 EIA 诊断为合格病例的患者。参与者按 1:1 随机分配，在使用标准护理 (SOC) 抗生素后，接受单剂量口服 CP101（6 x 1011 CFU 的冻干微生物细胞）或安慰剂。主要疗效终点是在第 8 周内无 CDI 复发的参与者比例。对第8周和24周的安全性、疗效和微生物组终点进行了评估，分析了198名参与者的结果；CP101（n=102）和安慰剂（n=96）。总体而言，27.5%的患者首次复发，62.7%通过PCR检测确诊。与安慰剂相比，CP101 组在第 8 周未复发 CDI 的比例明显更高（74.5% [76/102] vs 61.5% [59/96]，p=0.0488），且疗效持续到第 24 周（73.5% [75/102] vs 59.4% [57/96]，p=0.0347）。无论诊断方式或CDI复发次数如何，都观察到了相似的疗效。与安慰剂相比，CP101 组的微生物群多样性出现了快速而持久的增长。两组的不良反应发生率相似。结论CP101在减少CDI复发方面优于安慰剂，其安全性与安慰剂相似。https://clinicaltrials.gov/study/NCT03110133。

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来源期刊

Gastroenterology 医学-胃肠肝病学

CiteScore

45.60

自引率

2.40%

发文量

4366

审稿时长

26 days

期刊介绍： Gastroenterology is the most prominent journal in the field of gastrointestinal disease. It is the flagship journal of the American Gastroenterological Association and delivers authoritative coverage of clinical, translational, and basic studies of all aspects of the digestive system, including the liver and pancreas, as well as nutrition. Some regular features of Gastroenterology include original research studies by leading authorities, comprehensive reviews and perspectives on important topics in adult and pediatric gastroenterology and hepatology. The journal also includes features such as editorials, correspondence, and commentaries, as well as special sections like "Mentoring, Education and Training Corner," "Diversity, Equity and Inclusion in GI," "Gastro Digest," "Gastro Curbside Consult," and "Gastro Grand Rounds." Gastroenterology also provides digital media materials such as videos and "GI Rapid Reel" animations. It is abstracted and indexed in various databases including Scopus, Biological Abstracts, Current Contents, Embase, Nutrition Abstracts, Chemical Abstracts, Current Awareness in Biological Sciences, PubMed/Medline, and the Science Citation Index.