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.

While novel microbiome therapeutics gain approval, the efficacy of a full-spectrum, oral microbiome therapeutic is unknown.

尽管新型微生物组治疗药物获得批准，但全谱口服微生物组治疗的疗效尚不明确。

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.

本研究旨在确定CP101的安全性和有效性，CP101是一种口服微生物组治疗药物，旨在恢复微生物多样性并预防广泛人群中的复发性艰难梭菌感染(CDI)。

Methods

We conducted a multicenter, phase 2, double-blind, randomized, placebo-controlledtrial in adults with recurrent CDI.

我们在成人复发性CDI患者中进行了一项多中心、II期、双盲、随机、安慰剂对照试验。

Participants with one or more CDI recurrences and diagnosis by polymerase chain reaction or toxin enzyme immunoassay for the qualifying episode were included.

符合标准的参与者包括那些有一次或多次复发的艰难梭菌感染（CDI）患者，且通过聚合酶链反应或毒素酶免疫测定法确诊为限定发作期的病例。

Participants were randomized 1:1 to receive a single oral dose of either CP101 (∼6 × 1011 colony-forming units of lyophilized microbial cells) or placebo after standard-of-care antibiotics.

参与者按1:1的比例随机接受单一口服剂量的CP101（约6 × 10^11个冻干微生物细胞的菌落形成单位）或安慰剂，均在标准护理抗生素治疗后进行。

The primary efficacy endpoint was the proportion of participants without CDI recurrence through week 8.

主要疗效终点是第8周时无艰难梭菌感染（CDI）复发的参与者比例。

Safety, efficacy, and microbiome endpoints were evaluated through weeks 8 and 24.

安全性、疗效和微生物组终点在第8周和第24周进行评估。

Results

A total of 198 participants were analyzed: CP101 (n = 102) and placebo (n = 96).

共有198名参与者被分析：CP101组(n = 102)和安慰剂组(n = 96)。

Overall, 27.5% had a first recurrence, and 62.7% were diagnosed by polymerase chain reaction-based testing.

总体来看，27.5%的患者首次复发，62.7%的患者通过基于聚合酶链反应的检测被诊断。

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).

在第8周时，CP101组与安慰剂组相比，无CDI复发的比例显著更高（分别为74.5% [76/102]和61.5% [59/96]；P = .0488），并且这种持久的疗效在第24周时仍然观察到（分别为73.5% [75/102]和59.4% [57/96]；P = .0347）。

Similar efficacy was observed regardless of diagnostic modality or number of CDI recurrences.

无论诊断方式或CDI复发次数如何，观察到的疗效相似。

Rapid and durable increase in microbiome diversity was observed in the CP101 group compared to the placebo group.

与安慰剂组相比，CP101组的微生物群多样性迅速且持久地增加。

The incidenceof adverse events was similar between the 2 groups.

两组之间不良事件的发生率相似。

Conclusions

CP101 was superior to placebo in reducing recurrent CDI with a safety profile similar to placebo.

CP101在减少复发性艰难梭菌感染（CDI）方面优于安慰剂，并且其安全性与安慰剂相似。

(ClinicalTrials.gov, Number NCT03110133).

(ClinicalTrials.gov, 注册号NCT03110133).