Trial of Investigational Drug Finds Improved Health-Related Quality of Live in Patients with Recurrent C. Diff

A secondary analysis of a phase 3 clinical trial with SER-109, an investigational microbiome therapeutic, found rapid and steady improvement in health-related quality of life (HRQOL) compared with placebo through 8 weeks in patients with recurrent Clostridioides difficile infection (CDI).

Recurrent CDI is a debilitating disease that results in poor HRQOL, loss of productivity, anxiety, and depression. The investigators noted that a previous study demonstrated a 46% lower HRQOL as measured by the EuroQol index in adults hospitalized with CDI and compared with age- and gender-matched population norms. Despite this, the potential association of treatment with HRQOL has not been well evaluated, according to the authors of the current study.

SER-109 is an oral investigational microbiome therapeutic comprised of live purified Firmicutes bacterial spores designed to compete metabolically with C difficile and restore colonization resistance to C. difficile. In a recent phase 3, double-blind, randomized clinical trial, SER-109 was observed to be superior to placebo in reducing the risk of CDI recurrence up to 8 weeks of dosing and was well-tolerated.

The new study was a secondary analysis of a randomized, double-blind, placebo-controlled trial that took place at 56 sites in the United States and Canada from July 2017 to April 2020. It included 182 patients who were randomized to receive either SER-109 or placebo. The main outcome was an exploratory analysis of HRQOL using the disease-specific C. diff Quality of Life Survey (Cdiff32) assessed at baseline, week 1, and week 8.

Of the 182 patients, 59.9% were female with a mean age of 65.5 years. Additionally, 48.9% (N=89) were randomized to the SER-109 treatment group while 51.1% (N=93) were randomized to placebo. Baseline Cdiff32 scores were similar between both arms.

According to the study, the proportion of patients with overall improvement from baseline in the Cdiff32 total score was higher in the SER-109 arm than placebo at week 1 (49.4% vs 26.9%) and week 8 (66.3% vs 48.4%). Greater improvements in total and physical domain and subdomain scores were observed in patients in the SER-109 group compared with placebo as early as week 1, and continued improvements were observed at week 8.

Among the patients in the placebo group, improvements in HRQOL were primarily observed in patients with nonrecurrent CDI, whereas patients in the SER-109 group reported improvements in HRQOL regardless of clinical outcome.

The association between on-study CDI recurrence at week 8 and HRQOL was evaluated in the overall population. The investigators found significant differences in Cdiff32 total and all domain and subdomain scores between patients who experienced on-study recurrence versus those without recurrence. Patients without on-study recurrence reported significantly greater improvements from baseline compared with patients who experienced on-study recurrence through week 8.

However, these outcomes differed when examined within each treatment arm. In the placebo arm, only patients without on-study CDI recurrence had significant improvements in Cdiff32 scores at week 8. Patients in the placebo group who experienced on-study CDI recurrence generally showed decreased Cdiff32 scores and significant differences by CDI recurrence status were observed in total and all domain and subdomain scores at week 8.

Based on these findings, the investigators concluded that treatment with SER-109 was significantly associated with improved disease-specific HRQOL at week 8 after dosing compared with placebo. In addition to the previously observed clinical benefit, these findings mark the first evidence of improved HRQOL scores following treatment with an investigational microbiome agent.

REFERENCE

Garey K, Jo J, Gonzales-Luna A, et al. Assessment of Quality of Life Among Patients With Recurrent Clostridioides difficile Infection Treated with Investigational Oral Microbiome Therapeutic SER-109. JAMA Netw Open. 2023;6(1):e2253570. doi:10.1001/jamanetworkopen.2022.53570