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.

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