The effect of a microbial ecosystem therapeutic (MET-2) on recurrent Clostridioides difficile infection: a phase 1, open-label, single-group trial

2021 ◽  
Author(s):  
Dina Kao ◽  
Karen Wong ◽  
Rose Franz ◽  
Kyla Cochrane ◽  
Keith Sherriff ◽  
...  
Keyword(s):  
Phase 1 ◽  
Single Group ◽  
Open Label ◽  
Microbial Ecosystem ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
Group Trial

scholarly journals 701. An Open-label Phase 2a Study of Ibezapolstat, a Unique Gram-positive Selective Spectrum (GPSS) Antibiotic, for Patients with Clostridioides difficile Infection

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S451-S451
Author(s):  
Kevin W Garey ◽  
Khurshida Begum ◽  
Chenlin Hu ◽  
Weiqun Wang ◽  
Chris Lancaster ◽  
...  
Keyword(s):  
Clinical Cure ◽  
Phase 1 ◽  
Systemic Exposure ◽  
Clinical Development ◽  
Open Label ◽  
Gram Positive ◽  
Clostridioides Difficile ◽  
Open Label Phase ◽  
Clostridioides Difficile Infection ◽  
Stool Samples

Abstract Background Ibezapolstat, a DNA polymerase IIIC inhibitor, currently in Phase 2 clinical development for treatment of C. difficile infection (CDI). Its unique mechanism of action targets low G+C content Gram-positive bacteria primarily Firmicutes including C. difficile. Phase I healthy volunteer results demonstrated a favorable microbiome profile suggestive of an anti-recurrence effect. The purpose of this study was to report clinical outcomes, pharmacokinetics, and microbiome changes from this Phase 2a clinical study and to continue to test for anti-recurrence microbiome properties. Methods Ibezapolstat 450 mg was given twice daily for 10 days to patients with mild-moderate CDI defined as diarrhea plus a positive C. difficile toxin test. Test of cure was evaluated at day 12 and sustained clinical cure at day 38. Stool samples were evaluated for C. difficile cultures and microbiome changes. Results Ten subjects (female: 50%) aged 50 ±15 years were enrolled. All ten subjects experienced a clinical cure by the test of cure visit at day 12 and all 10 subjects experienced a sustained clinical cure at the day 38 visit. Ibezapolstat was well tolerated with 1 adverse event (nausea) probably related to drug. Ibezapolstat systemic exposure was minimal with no plasma level reaching 1 ug/mL any time during therapy. Ibezapolstat colonic concentrations averaged 400 ug/g stool at day 3 and greater than 1,000 ug/g by day 10 of dosing. Six of the seven available baseline stool samples grew toxigenic C. difficile of various ribotypes including RT078-226 and RT014-020 (Ibezapolstat MIC range: 0.25-1 ug/mL). Follow-up cultures were no growth starting from day 3 stool cultures. Microbiome changes included overgrowth of Actinobacteria and/or Firmicute phylum species while on therapy. Conclusion Favorable clinical efficacy and safety results were observed in ibezapolstat patients with CDI including 100% clinical cure and sustained clinical cure. These results begin to validate our approach to ibezapolstat development in that the favorable microbiome effects seen in healthy Phase 1 volunteers may be predictive of beneficial patient outcomes, including low rates of recurrence. These results support the continued clinical development of ibezapolstat. Disclosures Kevin W. Garey, Pharm.D., M.S., FASHP, Summit Therapeutics (Research Grant or Support) Michael Silverman, MD, Acurx Pharmaceuticals (Consultant)

scholarly journals 1042. Safety of Investigational Microbiota-Based Live Biotherapeutic RBX2660 in Individuals with Recurrent Clostridioides difficile Infection: Data from Five Prospective Clinical Studies

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S611-S611
Author(s):  
Tricia Braun ◽  
Beth Guthmueller ◽  
Adam J Harvey
Keyword(s):  
Clinical Studies ◽  
Ad Hoc ◽  
Safety Data ◽  
Standard Of Care ◽  
Oral Antibiotic ◽  
Open Label ◽  
Two Phase ◽  
Oral Antibiotic Therapy ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection

Abstract Background Microbiota-based treatments have shown promise to reduce recurrence, morbidity, and mortality for recurrent Clostridioides difficile infections (rCDI), but consistent and reliable safety data are needed to support regulatory approvals and broaden patient access. Here we provide cumulative safety data from 5 prospective clinical studies evaluating RBX2660—a standardized, microbiota-based investigational live biotherapeutic—for reducing rCDI. Methods This analysis included three Phase 2 (PUNCH CD, PUNCH CD2, PUNCH CD Open Label) and two Phase 3 trials (PUNCH CD3, PUNCH CD3-OLS ad hoc analysis). Participants were ≥18 years old with documented rCDI who completed standard-of-care oral antibiotic therapy prior to treatment with RBX2660. PUNCH CD3-OLS allowed participants with comorbidities of irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD). Depending on the trial, assigned study treatment was 1 or 2 doses of RBX2660 (or placebo), administered rectally. Participants whose CDI recurred within 8 weeks were eligible for additional RBX2660 treatment. Treatment-emergent adverse events (TEAEs) were recorded for at least 6 months following last study treatment; CD2 and CD Open Label recorded TEAEs for 24 months. Results Among 620 participants who received at least one RBX2660 dose (assigned treatment or after recurrence), 324 (52.3%) received 1, 270 (43.5%) received 2, 14 (2.3%) received 3, and 12 (1.9%) received 4. 83 participants received blinded placebo only. A total of 1980 TEAEs were reported from 432 (69.7%) RBX2660-treated participants, compared to 174 TEAEs in 50 (60.2%) placebo-only treated participants. Most TEAEs were mild or moderate in severity, with diarrhea common in all treatment groups. No potentially life-threatening TEAEs were considered related to RBX2660. Study discontinuation due to TEAEs was minimal (< 1%) with none related to RBX2660. There were no reported infections for which the causative pathogen was traced to RBX2660. Conclusion Across five clinical studies with consistent investigational product, RBX2660 was well-tolerated in rCDI participants. In aggregate, this data provides compelling and consistent safety data for RBX2660. Disclosures Tricia Braun, PharmD, Rebiotix, a Ferring Company (Employee) Beth Guthmueller, AS, Rebiotix Inc, A Ferring Company (Employee) Adam J. Harvey, PhD, Rebiotix, A Ferring Company (Employee)

39 EFFECT OF MICROBIAL ECOSYSTEM THERAPEUTICS (MET-2) ON RECURRENT CLOSTRIOIDES DIFFICILE INFECTION: AN OPEN-LABEL, SINGLE-GROUP PRELIMINARY STUDY

2020 ◽  
Vol 158 (6) ◽  
pp. S-15
Author(s):  
Dina H. Kao ◽  
Karen Wong ◽  
Rose Franz ◽  
Brandi Roach ◽  
Kyla Cochrane ◽  
...  
Keyword(s):  
Single Group ◽  
Open Label ◽  
Microbial Ecosystem ◽  
Preliminary Study

scholarly journals The Safety, Efficacy, and Tolerability of Microbial Ecosystem Therapeutic-2 in People With Major Depressive Disorder and/or Generalized Anxiety Disorder: A Phase 1, Open-Label Study

2021 ◽  
Author(s):  
Arthi Chinna Meyyappan ◽  
Evan Forth ◽  
Roumen Milev
Keyword(s):  
Major Depressive Disorder ◽  
Anxiety Disorder ◽  
Adverse Events ◽  
Depressive Disorder ◽  
Phase 1 ◽  
Generalized Anxiety ◽  
Depression And Anxiety ◽  
Open Label ◽  
Major Depressive ◽  
Microbial Ecosystem

Abstract Background: Recent studies have investigated the potential of treatments that modify the gut microbiome, such as fecal microbiota transplantation (FMT) and probiotics, in individuals with psychiatric illnesses. The aim of this study was to investigate the safety, tolerability, and efficacy of a novel gut microbiome therapeutic, Microbial Ecosystem Therapuetic-2 (MET-2), in people with depression and anxiety. Methods: In this phase 1, open-label trial, twelve adults diagnosed with Major Depressive Disorder and/or Generalized Anxiety Disorder were recruited. Participants consumed orally once daily an encapsulated microbial therapeutic, containing 40 strains of bacteria purified and lab-grown from a single healthy donor stool, for 8 weeks. Participants were assessed biweekly using clinical scales and questionnaires in order to evaluate the safety, efficacy, and tolerability of the therapeutic. Results: The therapeutic was found to be generally safe and tolerable, with limited adverse events and side effects, and no serious adverse events. Of the twelve individuals included in this study, nine responded to treatment (50% improvement in MADRS and/or GAD-7 scores from baseline to week 8 visit). Over the course of 10 weeks MET-2 significantly decreased mean MADRS and GAD-7 scores, MADRS [F (5, 55) = 8.784, p<0.0001 and GAD-7 F (5,55) = 9.638, p<0.0001]. Conclusion: The findings of this study are the first to provide evidence for the role of microbial ecosystem therapy in treating depression and anxiety. However, a double-blind, randomized controlled trial with a larger sample size is needed for more conclusive results. Trial Registration: This study was registered with clinicaltrials.gov (NCT04052451) on 09/08/2019.

scholarly journals Effectiveness of Oral Vancomycin for Prevention of Healthcare Facility–Onset Clostridioides difficile Infection in Targeted Patients During Systemic Antibiotic Exposure

2019 ◽  
Vol 71 (5) ◽  
pp. 1133-1139 ◽  
Author(s):  
Steven W Johnson ◽  
Shannon V Brown ◽  
David H Priest
Keyword(s):  
Medical Center ◽  
Healthcare Facility ◽  
Antibiotic Exposure ◽  
Oral Vancomycin ◽  
Open Label ◽  
Systemic Antibiotic ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
Gastrointestinal Side Effects ◽  
Systemic Antibiotics

Abstract Background Limited retrospective data suggest prophylactic oral vancomycin may prevent Clostridioides difficile infection (CDI). We sought to evaluate the effectiveness of oral vancomycin for the prevention of healthcare facility–onset CDI (HCFO-CDI) in targeted patients. Methods We conducted a randomized, prospective, open-label study at Novant Health Forsyth Medical Center in Winston-Salem, North Carolina, between October 2018 and April 2019. Included patients were randomized 1:1 to either oral vancomycin (dosed at 125 mg once daily while receiving systemic antibiotics and continued for 5 days postcompletion of systemic antibiotics [OVP]) or no prophylaxis. The primary endpoint was incidence of HCFO-CDI. Secondary endpoints included incidence of community-onset healthcare facility–associated CDI (CO-HCFA-CDI), incidence of vancomycin-resistant Enterococci (VRE) colonization after receiving OVP, adverse effects, and cost of OVP. Results A total of 100 patients were evaluated, 50 patients in each arm. Baseline and hospitalization characteristics were similar, except antibiotic exposure. No events of HCFO-CDI were noted in the OVP group compared with 6 (12%) in the no-prophylaxis group (P = .03). CO-HCFA-CDI was identified in 2 patients who were previously diagnosed with HCFO-CDI. No patients developed new VRE colonization, with only 1 patient reporting mild gastrointestinal side effects to OVP. A total of 600 doses of OVP were given during the study, with each patient receiving an average of 12 doses. Total acquisition cost of OVP was $1302, $26.04 per patient. Conclusion OVP appears to protect against HCFO-CDI during in-patient stay in targeted patients during systemic antibiotic exposure. Further prospective investigation is warranted.

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