S131 CP101, an Investigational Orally Administered Microbiome Therapeutic, Increases Intestinal Microbiome Diversity and Prevents Recurrent C. difficile Infection: Results From a Randomized, Placebo-Controlled Trial
Bibliographic record
Abstract
Introduction: Microbiome diversity is a surrogate marker for microbiome health with decreased diversity observed in many diseases. Key to disease pathogenesis in recurrent Clostridioides difficile infection (CDI) is decreased microbiome diversity and impaired colonization resistance. CP101 is an investigational orally administered microbiome therapeutic designed to restore microbiome diversity and enable early intervention in the management of recurrent CDI. Microbiome diversity is a key pharmacodynamic marker in recurrent CDI; however, data on the impact of increasing diversity on efficacy is scarce. Methods: We conducted a double-blind, randomized, placebo-controlled trial (PRISM3) enrolling adults who received standard-of-care antibiotics for recurrent CDI. Patients with first CDI recurrence at high-risk for further recurrence (≥65 years), or those with two or more recurrences were eligible. The qualifying CDI episode was diagnosed prior to study entry by guideline recommended testing (PCR-based or toxin EIA-based). Following CDI antibiotics, participants completed a minimum 2-day washout period. Eligible participants were randomized 1:1 to receive one-time oral administration of CP101 or placebo without bowel preparation. The primary efficacy endpoint was sustained clinical cure, defined as an absence of CDI recurrence through Week 8 following dosing. Diversity of the intestinal microbiome was measured at baseline, Week 1, and Week 8 using 16S rRNA gene amplicon sequencing. Results: Among the 198 enrolled participants analyzed, the CP101 arm demonstrated a statistically significant and clinically meaningful improvement in sustained clinical cure compared to placebo through Week 8 (74.5% [76/102] vs 61.5% [59/96], P=0.0488). Alpha diversity was low in the CP101 and placebo arms at baseline, and similar between both groups. Participants treated with CP101 achieved significantly higher alpha diversity compared to placebo, and the increase in diversity was rapid and sustained over time (p< 0.001 at Week 1, p< 0.0001 at Week 8) (Fig. 1a). Participants who received CP101 also had a significantly greater change in their microbial community composition from baseline compared to placebo at Week 1 (p< 0.001). Clinically, an increase in microbiome diversity at Week 1 was associated with sustained clinical cure through Week 8 (p< 0.001) (Fig. 1b). Conclusion: These data suggest that CP101 restores microbiome diversity, leading to colonization resistance and driving sustained clinical cure in recurrent CDI.Figure 1.: a. CP101 drives restoration of microbiome diversity. B. An increase in microbiome diversity at Week 1 is associated with sustained clinical cure through Week 8.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.004 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.003 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.010 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".