RBX2660 is Safe, Superior to Antibiotic-Treated Controls for Preventing Recurrent Clostridium difficile, and May Rehabilitate Patient Microbiomes: Open Label Trial Results
Notice bibliographique
Résumé
Effective treatment options for recurrent C. difficile infection (rCDI) are limited, 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 2 clinical trial. Herein we report results from a subsequent open-label trial to evaluate the safety, efficacy, and microbiome altering-activity of RBX2660 for preventing rCDI. This prospective, multicenter, 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 2 doses of RBX2660 delivered via enema with doses 7 days apart. Efficacy was defined as absence of CDI at 8 weeks from the last dose and was compared with the 8-week CDI-free rate of subjects who received antibiotic treatment alone in a matched historical control arm. 16s rRNA analysis was conducted on stool samples that were voluntarily submitted from RBX2660-treated subjects at baseline, 7, 30, and 60 days after treatment, and operational taxonomic units were compared longitudinally. 132 RBX2660 and 110 historical control subjects were included from 31 and 4 centers, respectively, in the USA and Canada. RBX2660’s efficacy in preventing rCDI (78.8%) was higher than CDI-free rates in the Historical Control group (51.8%, P < 0.001). A total of 476 adverse events (AEs) were reported by 97 RBX2660 subjects (73.5%) compared with 691 AEs among 69 historical controls (62.7%). Following treatment, the diversity of the RBX2660 treated subjects’ microbiomes significantly increased and the relative proportion of Bacteroidia and Clostridia, while decreasing the relative proportion of Gammaproteobacteria. The resulting RBX2660-treated subject microbiota more closely resembled healthy donors than at study entry. This open-label Phase 2 study demonstrates RBX2660’s efficacy in preventing rCDI compared with an antibiotic-treated historical control group. The RBX2660 safety profile is consistent with results from previous clinical trials and microbiota analysis suggests that RBX2660 may rehabilitate patient microbiota. This analysis was funded by Rebiotix Inc., Roseville, MN. 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; 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; S. Carter, Rebiotix, Inc.: Research Contractor, Consulting fee
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,004 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,002 | 0,000 |
| Communication savante | 0,002 | 0,001 |
| Science ouverte | 0,001 | 0,003 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».