Efficacy and Safety of RBX2660 for the Prevention of Recurrent Clostridium difficile Infection: Results. of the PUNCH CD 2 Trial
Bibliographic record
Abstract
Background. Restoration of the intestinal microbiota is highly efficacious in preventing recurrent Clostridium difficile infection (CDI). RBX2660 is a microbiota-based drug targeted at recurrent CDI. PUNCH CD 2, a multicenter, randomized, placebo-controlled, double-blinded Phase 2b trial was conducted to evaluate the safety and efficacy of RBX2660, including questions about dosing strategy and enema administration. Methods. Patients were randomized to receive: 2 doses of RBX2660 (Group A); 2 doses of placebo (Group B); or 1 dose of RBX2660 and 1 dose of placebo (Group C) via enema with doses 7 days apart. The primary end point was treatment success following 2 doses of RBX2660 compared with 2 doses of placebo. Success was defined as the absence of Clostridium difficile–associated diarrhea at 56 days following completion of the assigned treatment. Failures could receive up to 2 doses of open-label active treatment, 7 days apart. Secondary end points included overall efficacy and safety. Safety was assessed via a patient diary and clinical assessment. Results. A total of 150 patients at 21 sites in the United States and Canada were enrolled in the study. Of these, 127 patients (Group A: n = 41; Group B: n = 44; Group C: n = 42) were in the intention-to-treat population (mean age 61 years; 62.2% female). Efficacy for Group A was 61% versus 45.5% for Group B, P = 0.152. Efficacy for Group C was 66.7% compared with Group B (45.5%), P = 0.048. Efficacy for Group A and C (63.9%) versus B (45.5%), P = 0.046. For patients who developed recurrent CDI after receipt of the study drug, open-label treatment success was: Group A (68.8%, 11/16); Group B (87.5%, 21/24); Group C (71.4%; 10/14) for an overall open-label success rate of 77.8%. The combined efficacy for all patients who received at least 1 active treatment, including those who received open label RBX2660 after initial treatment failure, was 88.8% (n = 95). Adverse events (AEs) at 56 days were primarily gastrointestinal; there were no unanticipated AEs. There was no significant difference in the proportion of adverse or serious AEs among the treatment groups. Conclusion. In patients with recurrent CDI, a single dose of RBX2660 was superior to placebo, and showed equivalent efficacy as 2 doses. RBX2660 administered via enema was safe. Disclosures. E. R. Dubberke, Rebiotix Inc.: Scientific Advisor, Consulting fee and Research support Merck: Consultant and Investigator, Consulting fee and Research grant Sanofi Pasteur: Consultant and Grant Investigator, Consulting fee and Grant recipient Summitt: Consultant, Consulting fee C. Lee, Rebiotix Inc.: Investigator and Scientific Advisor, Consulting fee and Research support R. Orenstein, Rebiotix Inc.: Investigator and Scientific Advisor, Consulting fee and Research support S. Khanna, Rebiotix Inc.: Investigator and Scientific Advisor, Consulting fee and Research support G. Hecht, Rebiotix Inc.: Investigator and Scientific Advisor, Consulting fee and Research support J. Fraiz, Rebiotix Inc.: Investigator, Research support
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".