Sahil Khanna MBBS, Darrell S. Pardi MD, Dale N. Gerding MD, Ken Blount PhD, Courtney Jones, Bill Shannon PhD MBA, Elena Deych MS
- Microbiota-based therapies are demonstrating efficacy in preventing recurrent Clostridium difficile infections (rCDI).
- RBX7455 is a first-of-its-kind, lyophilized, non-frozen, orally-administered microbiota-restoring drug candidate that was developed for ease-of-use for rCDI patients.
- Herein we present an interim analysis of clinical safety and efficacy of a Phase 1 investigator-sponsored trial of RBX7455 for preventing rCDI, and we present an accompanying study of microbiome restoration among trial participants.
Clinical Trial Design & Methods
- Prospective, single-center, open-label Phase I investigator-initiated trial (NCT02981316)
- Inclusion criteria: >18 years old with documentation of recurrent CDI, at least one recurrence after a primary episode and has completed at least two rounds of standard-of-care oral antibiotic therapy; diarrhea resolved, i.e., fewer than 3 watery bowel movements at the time of study enrollment for 48 hours or more; a positive stool test for the presence of C. difficile within
30 days prior to enrollment and standard C. difficile treatment.
- Exclusion criteria: Known history of continued CDI diarrhea despite antibiotic treatment for CDI; requirement of continuous antibiotic therapy for a condition other than CDI; previous fecal transplant; previous treatment with RBX2660; history of inflammatory bowel disease(ulcerative colitis, Crohn’s disease, microscopic colitis), irritable bowel syndrome, chronic diarrhea, celiac disease; colostomy; evidence of active colitis; intended exposure to antibiotics within 6 months after study enrollment; compromised immune system (white blood cell count <1000 cells/μL); current or expected use of systemic steroids
- Antibiotics were discontinued 24-48 hours prior to first RBX7455 dose.
- Participants received 8 RBX7455 capsules per day for four days (Cohort 1) or two days (Cohort 2).
- Safety was assessed via a patient diary: in clinic at 1, 4, and 8 weeks and via telephone at 2, 3, between 5-7 weeks, and at 3, 6, 12 and 24 months.
- Success was defined as the absence of CDI at 8 weeks following completion of the last treatment. Treatment failure is defined as: recurrence of diarrhea <8 weeks after completion of RBX7455 treatment, a positive stool test for C. difficile, a need for retreatment for CDI, and no other cause for diarrhea.
- Stool samples were collected at baseline and at 7, 30, and 60 days and 24 weeks after treatment.
- 16 RBX7455 drug product samples and 84 stool samples from treatment responders were sequenced using an ultra-shallow shotgun method (CoreBiome, Minneapolis, MN).
- Multidimensional scaling analysis was performed on participant and RBX7455 operational taxonomic unit data according to a Bray-Curtis dissimilarity metric with non-metric scaling, and group mean relative taxonomic abundances at the class level were calculated by fitting to a Dirichlet-multinomial distribution
- In this open-label, investigator-sponsored Phase 1 study, both four and two days of RBX7455 dosing were effective at preventing rCDI.
- The RBX7455 safety profile is consistent with results from other clinical trials of microbiota-based therapies.
- Microbiota analysis suggests that RBX7455 restores a healthier microbiome composition.