Human Clinical Trial to Evaluate the Decolonization Efficacy of BM111 Against Carbapenem-Resistant Enterobacteriaceae (CRE) and Vancomycin-Resistant Enterococcus (VRE)

Official title

A Stratified, Randomized, Double-Blind, Placebo-Controlled Human Clinical Trial to Evaluate the Decolonization Efficacy of BM111 Against Carbapenem-Resistant Enterobacteriaceae (CRE) and Vancomycin-Resistant Enterococcus (VRE)

Overview

A clinical study to eliminate intestinal colonization in subjects harboring microorganisms resistant to carbapenem and vancomycin antibiotics, thereby treating infections caused by these microorganisms.

Interventions

• Dietary supplement BM111
  A mixture of four intestinal microorganisms
• Dietary supplement Placebo
  Placebo; Maltodextrin

Primary outcome measures

• Cumulative decolonization rate in the treatment and control groups after completion of BM111 administration [Time frame: From enrollment to the end of treatment at 8 weeks]

Secondary outcome measures (6)

• Time to decolonization in the treatment and control groups after completion of BM111 administration [Time frame: From enrollment to the end of treatment at 8 weeks]
• Changes in microbiome characteristics (e.g., diversity, microbial composition) in the treatment and control groups after completion of BM111 administration [Time frame: From enrollment to the end of treatment at 8 weeks]
• Reduction rate of CRE/VRE CFU per gram of stool after completion of BM111 administration [Time frame: From enrollment to the end of treatment at 8 weeks]
• Decolonization rate at Week 1, Week 4, and Week 8 after completion of BM111 administration [Time frame: From enrollment to the end of treatment at 8 weeks]
• Cumulative engraftment rate of BM111 effective strains [Time frame: From enrollment to the end of treatment at 8 weeks]
• Recurrence rate in subjects who achieved successful decolonization after completion of BM111 administration [Time frame: From enrollment to the end of treatment at 8 weeks]

Eligibility criteria

Inclusion criteria

• Subjects aged ≥19 years and <65 years
• Subjects with confirmed intestinal colonization of Carbapenem-resistant Enterobacteriaceae (CRE) or Vancomycin-resistant Enterococcus (VRE) at ≥10⁴ CFU per gram of stool at Visit 1
• Subjects who are carriers of CRE or VRE at Visit 1 and do not require treatment for CRE or VRE infection
• Subjects who are able to read and understand the informed consent document and agree to provide stool samples
• Subjects who voluntarily agree to participate in the study prior to initiation and provide written informed consent (Informed Consent Form)

Exclusion criteria

• Subjects whose CRE or VRE colonization in stool at Visit 2 has decreased by ≥10² CFU per gram compared to Visit 1
• Subjects with the following medical conditions or history:

• History of solid organ transplantation (e.g., heart, kidney, lung)

• Neutropenia

• Septic shock due to systemic inflammatory response syndrome (SIRS) or sepsis with persistent hypotension (systolic blood pressure <90 mmHg)

• Toxic megacolon or small bowel obstruction

• History of colectomy or colon resection ⑥ History of fecal microbiota transplantation (FMT)

• Epilepsy (seizure disorder), or history of recurrent seizures or cardiac arrest

• Severe anaphylaxis ⑨ Major gastrointestinal surgery (e.g., gastrectomy) within 3 months prior to Visit 1 (Appendectomy or cholecystectomy are allowed) ⑩ History of bacteremia within 2 weeks prior to Visit 1 ⑪ Pitt bacteremia score ≥4
• Subjects currently admitted to the intensive care unit (ICU) or requiring ICU admission due to severe illness
• Subjects requiring mechanical ventilation or vasopressor support (e.g., norepinephrine, ephedrine)
• Subjects receiving active treatment (chemotherapy, radiotherapy, biologic therapy, or maintenance chemotherapy) for active malignancy (including metastatic cancer)
• Subjects requiring treatment for central nervous system infections (e.g., meningitis, encephalitis, shunt infection)
• Subjects undergoing peritoneal dialysis
• Subjects with diarrhea caused by Clostridioides difficile infection
• Subjects with comorbidities that may pose risks during endoscopy or colonoscopy
• Severely immunocompromised subjects
• Subjects receiving high-dose immunosuppressants (e.g., glucocorticoids, azathioprine, 6-mercaptopurine, methotrexate, tacrolimus, cyclosporine, mycophenolate mofetil)(Participation may be allowed if deemed not to affect study outcomes by the investigator after review of dose, drug, and duration)
• Subjects requiring antibiotic or related treatment due to severe infection, or planning to use antibiotics during the study period
• Subjects who have taken gastric acid suppressants (e.g., PPIs), antibiotics, antidiarrheal agents, probiotics, prebiotics, or lactic acid bacteria products (≥4 times per week) within 1 week prior to Visit 1
• Subjects with BMI <17 kg/m² at Visit 1
• Subjects with clinically significant abnormal laboratory findings:

• Hemoglobin (Hb) < 8.0 g/dL ② Platelet count (PLT) < 75,000/mm³

• AST or ALT ≥3× the upper limit of normal (ULN)

• Total bilirubin >2× ULN ⑤ Albumin <3.2 mg/dL ⑥ Serum creatinine >2× ULN ⑦ HbA1c >8.0%
• Subjects with a life expectancy of less than 6 months
• Subjects unwilling or unable to use adequate contraception during the study period; Acceptable contraception methods include: intrauterine device (IUD/IUS), sterilization (vasectomy or tubal ligation), or dual barrier methods (e.g., cervical cap or diaphragm with male condom)
• Pregnant or breastfeeding women, or those planning pregnancy during the study period
• Subjects who participated in another interventional clinical trial within 3 months prior to Visit 1, or plan to participate in another interventional clinical trial during this study
• Subjects with hypersensitivity or allergy to food components or investigational product (IP) components
• Subjects deemed unsuitable for participation by the investigator for any other reason

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Single group

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

South Korea · 1 center

• Severance Hospital — Seoul

Identifiers

NCT: NCT07525089 · BioMe_BM111

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗