Safety and Tolerability of SYNB8802 in Healthy Adult Volunteers and Adult Subjects With Enteric Hyperoxaluria

Exclusion Criteria

• •1. Acute or chronic medical (including COVID-19 infection), surgical, psychiatric, or social condition or laboratory abnormality that may increase subject risk associated with study participation, compromise adherence to study procedures and requirements, or may confound interpretation of study safety or PD results and, in the judgment of the investigator, would make the subject inappropriate for enrollment.
• •2. Body mass index (BMI) \< 18.5 or \> 28 kg/m2.
• •3. Oxalobacter formigenes carrier.
• •4. Pregnant (self or partner), or lactating.
• •5. Unable or unwilling to discontinue vitamin C supplementation for the study duration.
• •6. History of or current immunodeficiency disorder including autoimmune disorders and human immunodeficiency virus (HIV) antibody positivity.
• •7. Hepatitis B surface antigen positivity (subjects with hepatitis B surface antibody positivity and hepatitis B core antibody positivity are not excluded, provided that the hepatitis B surface antigen is negative).
• •8. Hepatitis C antibody positivity, unless a hepatitis C virus ribonucleic acid test is performed, and the result is negative.
• •9. History of febrile illness, confirmed bacteremia, or other active infection deemed clinically significant by the investigator within 30 days prior to the anticipated first dose of IMP.
• •10. History of (within the past month) passage of 3 or more loose stools per day; where 'loose stool' is defined as a Type 6 or Type 7 on the Bristol Stool Chart (see Appendix 1: Bristol Stool Chart).
• •11. History of kidney stones, renal or pancreatic disease.
• •12. GI disorder (including inflammatory or irritable bowel disorder of any grade and surgical removal of bowel sections) that could be associated with increased UOx levels.
• •13. Active or past history of GI bleeding within 60 days prior to the Screening Visit as confirmed by hospitalization-related event(s) or medical history of hematemesis or hematochezia.
• •14. Intolerance of or allergic reaction to EcN, esomeprazole or PPIs in general, or any of the ingredients in SYNB8802 or placebo formulations.
• •15. Any condition (e.g., celiac disease, gastrectomy, bypass surgery, ileostomy), prescription medication, or over-the-counter product that may possibly affect absorption of medications or nutrients.
• •16. Currently taking or plans to take any type of systemic (e.g., oral or intravenous) antibiotic within 30 days prior to Day 1 through the final day of inpatient monitoring. Exception: topical antibiotics are allowed.
• •17. Major surgery (an operation upon an organ within the cranium, chest, abdomen, or pelvic cavity) or inpatient hospital stay within the past 3 months prior to Screening.
• •18. Planned surgery, hospitalizations, dental work, or interventional studies between Screening and last anticipated visit that might require antibiotics.
• •19. Taking or planning to take probiotic supplements (enriched foods excluded) within 30 days prior to Day -1 and for the duration of participation and follow-up.
• •20. Dependence on alcohol or drugs of abuse.
• •21. Administration or ingestion of an investigational drug within 30 days or 5 half-lives, whichever is longer, prior to Screening Visit; or current enrollment in an investigational study.
• •22. Screening laboratory parameters (e.g., chemistry panel, hematology, coagulation) and ECG outside of the normal limits based on standard ranges, or as defined in the table below, or as judged to be clinically significant by the investigator. A single repeat evaluation is acceptable.
• •1. Acute or chronic medical (including COVID-19 infection), surgical, psychiatric, or social condition or laboratory abnormality that may increase subject risk associated with study participation, compromise adherence to study procedures and requirements, or may confound interpretation of study safety or PD results and, in the judgment of the investigator, would make the subject inappropriate for enrollment.
• •2. Acute renal failure or eGFR \< 45 mL/min/1.73 m2. A single repeat evaluation is acceptable.
• •3. Unable or unwilling to discontinue vitamin C supplementation for the study duration.
• •4. Diagnosis of primary hyperoxaluria or any other cause of hyperoxaluria.
• •5. Oxalobacter formigenes carrier.
• •6. Pregnant (self or partner), or lactating.
• •7. Currently taking or plans to take any type of systemic (e.g., oral or intravenous) antibiotic within 30 days prior to Day 1 through the final safety assessment. Exception: topical antibiotics are allowed.
• •8. Major surgery (an operation upon an organ within the cranium, chest, abdomen, or pelvic cavity) or inpatient hospital stay within the past 3 months prior to Screening.
• •9. Planned surgery, hospitalizations, dental work, or interventional studies between Screening and last anticipated visit.
• •10. Taking or planning to take probiotic supplements (enriched foods excluded) within 30 days prior to Day -1 and for the duration of participation.
• •11. Intolerance of or allergic reaction to EcN, esomeprazole or PPIs in general, or any of the ingredients in SYNB8802 or placebo formulations.
• •12. Dependence on alcohol or drugs of abuse.
• •13. History of or current immunodeficiency disorder including autoimmune disorders and HIV antibody positivity.
• •14. Hepatitis B surface antigen positivity (subjects with hepatitis B surface antibody positivity and hepatitis B core antibody positivity are not excluded, provided that the hepatitis B surface antigen is negative).
• •15. Hepatitis C antibody positivity, unless a hepatitis C virus ribonucleic acid test is performed, and the result is negative.
• •16. Administration or ingestion of an investigational drug within 30 days or 5 half-lives, whichever is longer, prior to Screening Visit; or current enrollment in an investigational study.
• •17. History of bacteremia within 30 days prior to the anticipated first dose of IMP.
• •18. History of inflammatory bowel disease.