S144 CP101 Engraftment Drives Efficacy: Results From a Randomized, Placebo-Controlled Trial Evaluating CP101, an Investigational Orally Administered Microbiome Therapeutic for Prevention of Recurrent C. difficile Infection
Bibliographic record
Abstract
Introduction: Disruption of the microbiome is key to the pathogenesis of recurrent Clostridioides difficile infection (CDI). CP101 is an investigational orally administered microbiome therapeutic designed to restore microbiome diversity and enable early intervention in the management of recurrent CDI. Engraftment, the presence of administered microbes that colonize the gastrointestinal tract, is a key pharmacokinetic marker of microbiome therapeutics; however, there is a paucity of data on the impact of engraftment on clinical efficacy in recurrent CDI. 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 to limit the impact of residual antibiotics on CP101. 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. Engraftment of CP101 was measured 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). Participants treated with CP101 had significantly higher engraftment of CP101-associated taxa compared to placebo (Fig. 1a), and engraftment was both rapid and sustained over time (p< 0.0001 at Week 1, p< 0.0001 at Week 8). Clinically, CP101 engraftment was strongly associated with efficacy in recurrent CDI. Among participants with successful engraftment at Week 1 following CP101, 96.0% achieved a sustained clinical cure, while unsuccessful engraftment resulted in a 54.2% sustained clinical cure rate, similar to placebo following CDI antibiotics (p< 0.001) (Fig. 1b-c). Conclusion: These data suggest that successful CP101 engraftment drives high rates of sustained clinical cure in recurrent CDI. Future trials will deploy strategies to optimize engraftment by further minimizing the effect of residual CDI antibiotics.Figure 1.: a. CP101 showed significant engraftment in PRISM3. b. CP101 engraftment showed a bimodal distribution in PRISM3. c. CP101 engraftment strongly associated with sustained clinical cure in PRISM3.
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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 | 0.007 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.004 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.013 | 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".