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Record W2898601882 · doi:10.1093/ofid/ofy210.1606

1950. Prevention of Recurrent <i>Clostridium difficile</i> at Six Months Following Treatment With Microbiota-Based Therapy RBX2660: Durability Results From a Phase 2 Open-Label Study

2018· article· en· W2898601882 on OpenAlexaffabout
Sarah Mische, Robert Orenstein, Erik R. Dubberke, Sahil Khanna, Gail Hecht, Herbert L. DuPont, Christine Lee, Ken Blount

Bibliographic record

VenueOpen Forum Infectious Diseases · 2018
Typearticle
Languageen
FieldMedicine
TopicClostridium difficile and Clostridium perfringens research
Canadian institutionsMcMaster University
Fundersnot available
KeywordsMedicineClinical endpointClostridium difficileInternal medicinePhases of clinical researchOpen labelClinical trialAntibioticsSurgery

Abstract

fetched live from OpenAlex

Numerous microbiota-based therapies are being evaluated for prevention of C. difficile infection (rCDI), a public health threat with high recurrence rates associated with the current standard of care. RBX2660, a standardized microbiota-based drug, was efficacious for preventing rCDI in a double-blinded Phase 2b clinical study (PUNCH CD 2). Herein we report the durability of RBX2660 beyond the initial primary clinical end-point of a subsequent Phase 2 open-label study, demonstrating rCDI prevention at 6 months post-treatment. This prospective, multi-center, open-label Phase 2 study enrolled subjects who had experienced either ≥2 recurrences of CDI following standard-of-care antibiotic therapy or ≥2 episodes of severe CDI requiring hospitalization. Participants received up to two doses of RBX2660 delivered via enema with doses 7 days apart. The primary endpoint of the open-label clinical study defined efficacy as absence of CDI at 8 weeks from the last dose. Safety follow-ups and durability assessments occurred via telephone at 3, 6, 12, and 24 months. The study is ongoing, and not all subjects have completed their assessments. This study included 149 RBX2660-treated subjects and 110 historical control subjects from 31 and 4 centers, respectively, in the United States and Canada. At 8-weeks post-treatment, RBX2660’s efficacy in preventing rCDI (79.9%; 119/149) was higher than CDI-free rates in the historical control group (51.8%, 57/110; P < 0.001). Of the 119 subjects who were determined to be treatment success at 8 weeks, 117 have data through 6 months, of which 8 were exited for non-CDI reasons. Of those 109 subjects through the 6-month follow-up, 3 (2.8%) had a new CDI beyond 8 weeks after enema. The 6-month long-term CDI-free rate was 97.2% (106/109) (median follow-up: 182 days; mean: 177 days). RBX2660, a microbiota-based drug, was efficacious for the prevention of recurrent CDI with long-term durability at 6-months post-treatment; a result consistent with 6-month rCDI prevention reported for the Phase 2b PUNCH CD 2 trial. Long-term follow-up of RBX2660 safety and efficacy 24 months is ongoing. This analysis was funded by Rebiotix Inc., Roseville, MN. S. Mische, Rebiotix, Inc.: Employee, Salary. R. Orenstein, Rebiotix, Inc.: Scientific Advisor, Consulting fee. E. R. Dubberke, Rebiotix, Inc.: Scientific Advisor, Consulting fee. S. Khanna, Rebiotix, Inc.: Scientific Advisor, Consulting fee and Research support. G. Hecht, Rebiotix, Inc.: Scientific Advisor, Consulting fee. H. Dupont, Rebiotix, Inc.: Investigator, Research support. C. Lee, Rebiotix, Inc.: Scientific Advisor, Consulting fee. K. Blount, Rebiotix, Inc.: Employee, Salary.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Non-randomized trial · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.001

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.

Opus teacher head0.053
GPT teacher head0.374
Teacher spread0.321 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNon-randomized trial
Domainnot available
GenreEmpirical

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".

Quick stats

Citations0
Published2018
Admission routes2
Has abstractyes

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