Safety and Efficacy of Oral Administration of the Phage Cocktail, VRELysin™, In Healthy and VRE-Colonized Subjects

Exclusion Criteria

• •To be eligible to participate in Phase 1, subjects must NOT fulfill ANY of the following criteria:
• •1. Investigational research agents received within 30 days before first treatment.
• •2. Pregnant or breastfeeding.
• •3. Regular (no more than once a week) use of antidiarrheals, stool softeners, laxatives, antacids, or other agents to lower stomach acidity.
• •4. Use of oral or intravenous antimicrobials within 2 weeks of study start or planned use during active study phase. Topical treatments are allowed.
• •5. Proton pump inhibitors, H2 blockers or antacids within 48 hours prior to dosing or planned use during active study phase.
• •6. Abnormal bowel patterns, defined by \<3 stools per week or \>2 stools per day on average over the past 6 months.
• •7. History of diarrhea in the 7 days prior to treatment. Outpatient diarrhea is defined as ≥ 3 unformed (Grade 3 or greater) loose stools in 24 hours.
• •8. Use of oral supplemental probiotics in the form of pills or tablets within 2 weeks of study start or planned use during active study phase.
• •9. History of myocarditis, pericarditis, cardiomyopathy, congestive heart failure with permanent sequelae, clinically significant arrhythmia (including any arrhythmia requiring medication, treatment, or clinical follow-up).
• •10. Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. A clinically significant condition or process includes, but is not limited to:
• •1. Any contraindication to repeated blood draws;
• •2. A condition or process for which signs or symptoms could be confused with reactions to treatment;
• •3. Any of the following in the past 10 years: Crohn's disease, ulcerative colitis, irritable bowel disease, celiac disease, stomach, or intestinal ulcers, or 2 or more episodes of inflammatory arthritis (joint pain and swelling);
• •4. Bacterial infection at time of enrollment;
• •5. Blood in stool on \>2 occasions (other than small amounts from straining) in past 12 months;
• •6. Recurrent diarrhea (\>5 episodes in past 6 months, each lasting \>3 days or more).
• •11. History of excessive alcohol consumption or drug dependence within last 3 years.
• •12. Any medical, psychiatric, occupational, or other condition that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety, or a subject's ability to give informed consent.
• •13. Psychiatric condition that precludes compliance with the protocol. Specifically excluded are persons with psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years.
• •14. Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions).
• •15. Malignancy (Not excluded from participation: subject who has had malignancy excised surgically and who, in the investigator's estimation, has a reasonable assurance of sustained cure, or who is unlikely to experience recurrence of malignancy during the period of the study).
• •16. Seizure disorder/epilepsy: History of seizure(s) within past 3 years. Also exclude if subject has used medications in order to prevent or treat seizure(s) at any time within the past 3 years.
• •17. Asplenia: any condition resulting in the absence of a functional spleen.
• •18. History of chronic gastrointestinal illness, including severe dyspepsia, lactose intolerance, or other significant gastrointestinal tract disease (e.g., irritable bowel syndrome/disease, inflammatory bowel syndrome, gastric ulcer disease, Crohn's disease).
• •19. Any other criteria which, in the Investigator's opinion, would compromise the ability of the subject to participate in the study, the safety of the study, or the results of the study.
• •20. Known allergy or hypersensitivity to an excipient in the study drug or placebo.
• •To be eligible to participate in Phase 2a, subjects must NOT fulfill ANY of the following criteria:
• •1. Investigational research agents received within 30 days before first treatment.
• •2. Pregnant or breastfeeding.
• •3. Regular (no more than once a week) use of antidiarrheals, stool softeners, laxatives, antacids, or other agents to lower stomach acidity.
• •4. Use of oral or intravenous antimicrobials within 2 weeks of study start or planned use during active study phase. Topical treatments are allowed.
• •5. Proton pump inhibitors, H2 blockers or antacids within 48 hours prior to dosing or planned use during active study phase.
• •6. Abnormal bowel patterns, defined by \<3 stools per week or \>2 stools per day on average over the past 6 months.
• •7. History of diarrhea in the 7 days prior to treatment. Outpatient diarrhea is defined as ≥3 unformed (Grade 3 or greater) loose stools in 24 hours.
• •8. Taking supplemental probiotics in the form of pills or tablets within 2 weeks.
• •9. History of myocarditis, pericarditis, cardiomyopathy, congestive heart failure with permanent sequelae, clinically significant arrhythmia (including any arrhythmia requiring medication, treatment, or clinical follow-up).
• •10. Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. A clinically significant condition or process includes but is not limited to:
• •1. Any contraindication to repeated blood draws;
• •2. A condition or process for which signs or symptoms could be confused with reactions to treatment;
• •3. Any of the following in the past 10 years: Crohn's disease, ulcerative colitis, irritable bowel disease, celiac disease, stomach, or intestinal ulcers;
• •4. Blood in stool on \>2 occasions (other than small amounts from straining) in past 12 months;
• •5. Recurrent diarrhea (\>5 episodes in past 6 months, each lasting \>3 days or more);
• •6. Requires hemodialysis.
• •11. History of excessive alcohol consumption or drug dependence within last 3 years.
• •12. Any medical, psychiatric, occupational, or other condition that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety, or a subject's ability to give informed consent.
• •13. Psychiatric condition that precludes compliance with the protocol. Specifically excluded are persons with psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years.
• •14. Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions).
• •15. Malignancy (Not excluded from participation: subject who has had malignancy excised surgically and who, in the investigator's estimation, has a reasonable assurance of sustained cure, or who is unlikely to experience recurrence of malignancy during the period of the study).
• •16. Seizure disorder/epilepsy: History of seizure(s) within past 3 years. Also exclude if subject has used medications in order to prevent or treat seizure(s) at any time within the past 3 years.
• •17. Asplenia: any condition resulting in the absence of a functional spleen.
• •18. History of chronic gastrointestinal illness, including severe dyspepsia, lactose intolerance, or other significant gastrointestinal tract disease (e.g., irritable bowel syndrome, inflammatory bowel syndrome, gastric ulcer disease).
• •19. Known allergy or hypersensitivity to an excipient in the study drug or placebo.
• •20. Patients with active infection, a systemic infection requiring treatment, or any other unstable medical condition that could interfere with the study objectives.
• •21. Any other criteria which, in the Investigator's opinion, would compromise the ability of the subject to participate in the study, the safety of the study, or the results of the study.