A Safety Trial to Evaluate an Orally Ingested Yeast Modified to Express a Tetra-specific Anti-toxin for Clostridioides Difficile

Inclusion Criteria

• •To be eligible to participate in Part A of this trial, an individual must meet all of the following criteria:
• •1. Provides written informed consent prior to the initiation of any trial procedures.
• •2. Is able to understand and agrees to comply with all planned trial procedures and be available for all study visits, including:
• •1. Receiving 28 days of blinded oral study product
• •2. Providing blood and self-collected stool samples
• •3. Is a non-pregnant individual, aged 18-75 years, inclusive, at the time of enrollment.
• •4. Has no more than 1 single Grade 1 screening laboratory abnormality that is not clinically significant. If the participant has more than 1 Grade 1 abnormality, it must be approved by the Division of Microbiology and Infectious Diseases \[DMID\] Medical Monitor (MM).
• •5. Participants of childbearing potential: use of adequate contraception for at least 4 weeks prior to enrollment and agreement to use such a method during trial participation and for an additional 4 weeks after the last dose of blinded study product. Note: Definitions of participants of childbearing potential and adequate contraception are provided in Section 13.1.
• •6. Agrees to refrain from ingestion of probiotics\* or fermented foods\*\* from 7 days prior to study product administration, while on blinded study product, and through Day 36 (Visit 6).
• •\*E.g., probiotic nutritional Lactobacillus or Bifidobacterium supplements, yogurt, kefir, any "live and active culture" nutritional product, etc.
• •\*\*E.g., kombucha, fermented pickled vegetables, etc.
• •7. Has good health by medical history, vital signs, physical examination, and concomitant medication review\*. Participants should be stable based on their condition over the last 3 months prior to enrollment.
• •\*As defined by not requiring a change in therapy (including dose or frequency) or medical care for worsening disease for at least 3 months prior to enrollment. Vital signs must not meet Grade 1 or higher.
• •8. Not using medications daily that may affect gut motility, gastric acidity, or baseline gut function\* within 3 months of enrollment and through Day 36 (Visit 6).
• •\*E.g., proton pump inhibitors, opioids, anti-diarrheal agents, anti-constipation agents, daily Over-the-counter \[OTC\] "heartburn" relief medications.
• •9. Not using glucagon-like peptide-1 (GLP-1) receptor agonists within 6 weeks of enrollment.
• •10. Any elective surgery (including dental) that required preoperative or postoperative antibiotics must have been completed at least 3 months prior to enrollment.
• •11. No history of Clostridioides difficile infection \[CDI\] (suspected or proven), no recent hospital admissions (within 3 years), and no receipt of systemic antibiotics known to increase risk of CDI\* (within 6 months).
• •\*Systemic antibiotics that are known to increase the risk of CDI include lincosamides (e.g., clindamycin), monobactams (e.g., aztreonam), extended-spectrum penicillin combinations with beta-lactamase inhibitors (e.g., piperacillin-tazobactam), carbapenems (e.g., imipenem, meropenem, ertapenem), third generation or higher cephalosporins, and fluoroquinolones. Common oral antibiotics that would be allowable or are not known to significantly increase risk of CDI include amoxicillin, azithromycin, cephalexin, doxycycline, metronidazole, and trimethoprim/sulfamethoxazole.
• •12. No history of other enteric infections or diarrheal illness within 3 months of enrollment.
• •In order to be eligible to participate in Part B of this trial, an individual must meet all of the following criteria:
• •1. Provides written informed consent prior to the initiation of any trial procedures.
• •2. Is able to understand and agrees to comply with all planned trial procedures and be available for all study visits, including:
• •1. Receiving 28 days of blinded oral study product
• •2. Providing blood and self-collected stool samples
• •3. Is non-pregnant individual, aged 18-75 years, inclusive, at the time of enrollment.
• •4. Has no more than 1 single Grade 1 hematology result and no more than 1 Grade 1 metabolic panel result. If the participant has more than 1 Grade 1 abnormality, it must be approved by the MM.
• •5. Participants of childbearing potential: use of adequate contraception for at least 4 weeks prior to enrollment through 4 weeks after the last dose of blinded study product. Note: Definitions of participants of childbearing potential and adequate contraception are provided in Section 13.1.
• •6. To rule out live microbial products and factors that may actively modulate the gut microbiome, participant agrees to refrain from ingestion of probiotics\* or fermented foods\*\* from 7 days prior to study product administration, while on blinded study product, and through Day 36 (Visit 6).
• •\* E.g., probiotic nutritional Lactobacillus or Bifidobacterium supplements, yogurt, kefir, any "live and active culture" nutritional product, etc.
• •\*\* E.g., kombucha, fermented pickled vegetables, etc.
• •7. Stable health by medical history, vital signs, physical examination, concomitant medication review, not requiring a change in therapy or medical care for worsening disease within 1 month of enrollment.
• •8. Not using medications daily that may affect gut motility, gastric acidity, or baseline gut function\* within 1 month of enrollment.
• •\*E.g., proton pump inhibitors, opioids, anti-diarrheal agents, anti-constipation agents, daily OTC "heartburn" relief medications.
• •9. Not using GLP-1 receptor agonists within 6 weeks of enrollment.
• •10. Any elective surgery (including dental) that required preoperative or postoperative antibiotics must have been completed at least 1 month prior to enrollment.
• •11. Must have had at least 1 of these 3 conditions:
• •1. History of CDI (suspected or proven) within the past 3 years, with "cure" or no symptoms for at least 1 month prior to enrollment
• •2. History of a hospitalization within the past 3 years, but discharge not sooner than 1 month prior to enrollment
• •3. History of receiving systemic antibiotics known to increase the risk of CDI\* within the past 3 years, but last dose not sooner than 1 month prior to enrollment \*Systemic antibiotics that are known to increase risk of CDI include lincosamides (e.g., clindamycin), monobactams (e.g., aztreonam), extended-spectrum penicillin combinations with beta-lactamase inhibitors (e.g., piperacillin-tazobactam), carbapenems (e.g., imipenem, meropenem, ertapenem), third generation or higher cephalosporins, and fluoroquinolones. Common oral antibiotics that would be allowable or are not known to significantly increase the risk of CDI include amoxicillin, azithromycin, cephalexin, doxycycline, metronidazole, and trimethoprim/sulfamethoxazole.
• •12. No history of other enteric infections or diarrheal illness within 1 month of enrollment.