Overview

The study is a first-in-human Phase 1/2a randomized, double-blind, placebo-controlled trial to assess the clinical safety and efficacy of VRELysin in healthy and VRE-colonized adults.

Eligibility

PHASE 1 INCLUSION CRITERIA:

        To be eligible to participate in the Phase 1 segment of the study, each subject must
        fulfill ALL of the following criteria:
          1. Age 18 to 50 years old.
          2. Body mass index (BMI) of ≥19 kg/m2 to ≤40 kg/m2.
          3. Has the ability to understand the study procedures and risks involved with the study,
             voluntarily agrees to participate by giving written informed consent and is willing to
             adhere to dose and visit schedules. The subject must be able to read, understand, and
             complete questionnaires and memory aids.
          4. Agrees not to enroll in another study of an investigational research agent during the
             study, with the exception of potentially lifesaving or coronavirus disease of 2019
             (COVID-19)-related experimental treatments.
          5. Good general health as shown by medical history, physical examination, and screening
             laboratory tests or clinical laboratory abnormalities per clinical judgment of
             Principal Investigator (PI).
          6. Agrees not to donate blood or blood products during participation in the study or for
             30 days after completion of study participation.
          7. Has negative serology results for HIV, hepatitis B surface antigen (HBsAg), and
             hepatitis C virus (HCV) antibody.
          8. Female subjects must have a negative serum or urine beta human chorionic gonadotropin
             (β-HCG) pregnancy test at Screening and within 24 hours of initial treatment on Day 1.
             a. Persons who are NOT of reproductive potential due to having undergone total
             hysterectomy or bilateral oophorectomy (verified by medical records) are not required
             to undergo pregnancy testing.
          9. Female subjects of reproductive potential must agree to use adequate contraception,
             defined as consistent and correct use of an FDA-recommended contraceptive method or
             combination of methods in accordance with the product label. For example:
               1. Barrier method (such as condoms, diaphragm, or cervical cap) used in conjunction
                  with spermicide and another method, such as prescription hormonal contraceptive;
               2. Intrauterine device (IUD);
               3. Prescription hormonal contraceptive taken or administered via oral (pill),
                  transdermal (patch) subdermal, or intramuscular route used in combination with
                  another method, such as barrier methods;
               4. Total abstinence;
               5. Sterilization of a monogamous female participant's male partner prior to entry
                  into the study.
             Note: periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation
             methods) and withdrawal are not acceptable methods of contraception.
         10. Female subjects must also agree not to seek pregnancy through alternative methods,
             such as artificial insemination or in vitro fertilization until after the last
             required study visit is completed.
         11. Male subjects must agree to use adequate contraception, defined as consistent and
             correct use of an FDA-recommended contraceptive method in accordance with the product
             label (see above), for the duration of the study and refrain from donating sperm
             during this period.
        PHASE 1 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.
        PHASE 2A INCLUSION CRITERIA:
        To be eligible to participate in the Phase 2a segment of the study, each subject must
        fulfill ALL of the following criteria:
          1. Age 18 to 50 years old.
          2. BMI of ≥19 kg/m2 to ≤40 kg/m2.
          3. Has the ability to understand the study procedures and risks involved with the study,
             voluntarily agrees to participate by giving written informed consent and is willing to
             adhere to dose and visit schedules. The subject must be able to read, understand, and
             complete questionnaires and memory aids.
          4. Agrees not to enroll in another study of an investigational research agent during the
             study, with the exception of potentially lifesaving or COVID-19-related experimental
             treatments.
          5. Agrees not to donate blood or blood products during participation in the study or for
             30 days after completion of study participation.
          6. Has negative serology results for HIV, HBsAg, and HCV antibody.
          7. Has 2 consecutive positive VRE stool cultures (at least 7 days apart) that are
             susceptible to VRELysin. The second stool culture must be within 7 days of
             randomization.
          8. Able to tolerate and take oral medication at time of randomization.
          9. Female subjects must have a negative serum or urine β-HCG pregnancy test at Screening
             and within 24 hours of initial treatment on Day 1.
         10. Persons who are NOT of reproductive potential due to having undergone total
             hysterectomy or bilateral oophorectomy (verified by medical records) are not required
             to undergo pregnancy testing.
               1. Female subjects of reproductive potential must agree to use adequate
                  contraception, defined as consistent and correct use of an FDA-recommended
                  contraceptive method or combination of methods in accordance with the product
                  label. For example:
               2. Barrier method (such as condoms, diaphragm, or cervical cap) used in conjunction
                  with spermicide and another method, such as prescription hormonal contraceptive;
               3. IUD;
               4. Prescription hormonal contraceptive taken or administered via oral (pill),
                  transdermal (patch) subdermal, or intramuscular route used in combination with
                  another method, such as barrier methods;
               5. Total abstinence;
               6. Sterilization of a monogamous female participant's male partner prior to entry
                  into the study.
             Note: periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation
             methods) and withdrawal are not acceptable methods of contraception.
         11. Female subjects must also agree not to seek pregnancy through alternative methods,
             such as artificial insemination or in vitro fertilization until after the last
             required study visit is completed.
         12. Male subjects must agree to use adequate contraception, defined as consistent and
             correct use of an FDA-recommended contraceptive method in accordance with the product
             label (see above), for the duration of the study and refrain from donating sperm
             during this period.
        PHASE 2A EXCLUSION CRITERIA:
        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.