15-strain live biotherapeutic product or same donor fecal microbiota transplant for recurrent Clostridioides difficile infection: a randomized phase 1b trial.

In vitro manufactured live biotherapeutic products (LBPs) enable both scalability and defined strain composition but with higher manufacturing complexity, resulting in few LBP clinical trials.

体外制造的活菌生物治疗产品（LBPs）既可实现规模化生产，又可确保菌株组成明确，但其生产过程复杂性较高，导致目前进行的LBP临床试验数量有限。

Here we show how an accessible platform to produce human-grade LBPs could accelerate LBP development.

在这里，我们展示了如何利用一个可访问的平台来生产符合人类等级的LBPs（脂多糖结合蛋白），这可能会加速LBP的开发。

We provide regulatory documentation and manufacturing protocols to facilitate translating microbiome advances to human trials.

我们提供了监管文件和制造协议，以促进将微生物组的进展转化为人类试验。

With this platform, we conducted the first direct comparison of the same bacterial strains from donor-sourced FMT compared to an in vitro manufactured 15-strain LBP drug product, MTC01, for the treatment of rCDI.

在这个平台上，我们进行了首次直接比较，比较了来自供体来源的粪便微生物移植（FMT）与体外制造的15株菌群药物产品MTC01对治疗复发性艰难梭菌感染（rCDI）的效果。

In a phase 1b randomized controlled trial, 18 of 20 screened patients met eligibility and were randomized equally to one of four arms: low-dose FMT (n = 4), high-dose FMT (n = 5), low-dose MTC01 (n = 4) or high-dose MTC01 (n = 5), with a 5:1 female:male ratio.

在一项1b期随机对照试验中，20名筛选的患者中有18名符合资格，并被平均分配到四个组别：低剂量FMT（n=4），高剂量FMT（n=5），低剂量MTC01（n=4）或高剂量MTC01（n=5），女性与男性的比例为5:1。

The primary outcome of safety was met with 10 adverse events across eight patients, evenly spread across MTC01 (five events) and FMT (five events) recipients and no treatment-related adverse events across all four groups.

主要的安全性结果得到了满足，八名患者中共发生了10起不良事件，MTC01和FMT受试者之间均匀分布（各五起事件），所有四组中均未出现与治疗相关的不良事件。

For secondary outcomes of efficacy and engraftment, rCDI was prevented 8 weeks after dosing in seven out of nine LBP patients, similar to eight out of nine FMT patients.

次要的疗效和植入效果结果表明，在用药后8周，九名LBP患者中有七名预防了rCDI，与九名FMT患者中的八名相似。

Strain engraftment was high and durable for both FMT and MTC01 with a dose effect for the LBP.

FMT和MTC01的菌株植入率高且持久，且对于LBP存在剂量效应。

ClinicalTrials.gov: NCT05911997 .

ClinicalTrials.gov: NCT05911997 .