Ensayos clínicos

Inclusion Criteria:

• Age ≥ 18 to ≤ 74 years.
• Able and willing to voluntarily complete the informed consent process.
• Available for and agree to all study procedures, including feces, urine, and blood collection and adherence to diet control, follow-up visits, and compliance with all study procedures.
• Enteric hyperoxaluria secondary to Roux-en-Y bariatric surgery (at least 12 months post-surgery).
• Urinary oxalate ≥ 70 mg/24 hours (mean of at least 2 urine collections during Screening).
• Male subjects who are sexually abstinent or surgically sterilized (vasectomy), or those who are sexually active with a female partner(s) and agree to use an acceptable method of contraception (such as condom with spermicide) combined with an acceptable method of contraception for their non-pregnant female partner(s) (as defined in Inclusion Criterion #7) after informed consent, throughout the study, and for a minimum of 3 months after the last dose of IMP, and who do not intend to donate sperm in the period from Screening until 3 months following administration of the investigational medical product.
• Female subjects who meet 1 of the following:
  • Woman of childbearing potential (WOCBP) must have a negative pregnancy test (human chorionic gonadotropin) at Screening and at baseline prior to the start of IMP and must agree to use acceptable method(s) of contraception, combined with an acceptable method of contraception for their male partner(s) after informed consent, throughout the study and for a minimum of 3 months after the last dose of IMP. Acceptable methods of contraception include hormonal contraception, hormonal or non-hormonal intrauterine device, bilateral tubal occlusion, complete abstinence, vasectomized partner with documented azoospermia 3 months after procedure, diaphragm with spermicide, cervical cap with spermicide, vaginal sponge with spermicide, or male or female condom with or without spermicide.
  • Premenopausal woman with at least 1 of the following:
    • Documented hysterectomy;
    • Documented bilateral salpingectomy;
    • Documented bilateral oophorectomy;
    • Documented tubal ligation/occlusion;
    • Sexual abstinence is preferred or usual lifestyle of the subject.
  • Postmenopausal women (12 months or more amenorrhea verified by FSH assessment and over 45 years of age in the absence of other biological or physiological causes).

Inclusion Criteria - Part 2:

• Age ≥ 18 to ≤ 74 years.
• Able and willing to voluntarily complete the informed consent process.
• Available for and agree to all study procedures, including feces, urine, and blood collection and adherence to diet control, follow-up visits, and compliance with all study procedures.
• Enteric hyperoxaluria secondary to history of malabsorption after bariatric surgery or surgical short-bowel syndrome.
• Urinary oxalate ≥ 45 mg/24 hours (mean of 2 samples during screening). (Tier 1 urinary oxalate must be ≥ 40 mg/24 hours to be eligible for Tier 2 screening).
• If taking probiotic supplements (enriched foods excluded), has been on stable, well-tolerated dose for at least 2 weeks prior to Day 1.
• Male subjects who are sexually abstinent or surgically sterilized (vasectomy), or those who are sexually active with a female partner(s) and agree to use an acceptable method of contraception (such as condom with spermicide) combined with a recommendation for use of an acceptable method of contraception for their non-pregnant female partner(s) after informed consent, throughout the study, and for a minimum of 3 months after the last dose of IMP, and who do not intend to donate sperm in the period from screening until 3 months following administration of the investigational medical product.
• Female subjects who meet 1 of the following:
  • WOCBP must have a negative pregnancy test (human chorionic gonadotropin) at screening and at baseline prior to the start of IMP and must agree to use acceptable method(s) of contraception, combined with a recommendation for use of an acceptable method of contraception for their male partner(s) after informed consent, throughout the study and for a minimum of 3 months after the last dose of IMP. Acceptable methods of contraception include hormonal contraception, hormonal or non-hormonal intrauterine device, bilateral tubal occlusion, complete abstinence, vasectomized partner with documented azoospermia 3 months after procedure, diaphragm with spermicide, cervical cap with spermicide, vaginal sponge with spermicide, or male or female condom with or without spermicide;
  • Premenopausal woman with at least 1 of the following:
  • Documented hysterectomy;
  • Documented bilateral salpingectomy;
  • Documented bilateral oophorectomy;
  • Documented tubal ligation/occlusion;
  • Sexual abstinence is preferred or usual lifestyle of the subject c. Postmenopausal women (12 months or more amenorrhea verified by FSH assessment and over 45 years of age in the absence of other biological or physiological causes).
• Screening laboratory evaluations (e.g., chemistry panel, complete blood count with differential, prothrombin time [PT]/activated partial thromboplastin time [aPTT], urinalysis) and electrocardiogram (ECG) must be within normal limits or judged to be not clinically significant by the investigator. A single repeat evaluation is acceptable.

Exclusion Criteria:

• 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.
• Acute renal failure or estimated glomerular filtration rate <45 mL/min/1.73 m2.
• Unable or unwilling to discontinue vitamin C supplementation for the study duration
• Diagnosis of primary hyperoxaluria or any other cause of hyperoxaluria.
• Pregnant (self or partner), or lactating.
• Taking any type of systemic (e.g., oral or intravenous) antibiotic within less than 5 times the halflife of the antibiotic prior to Day 1.
  • Exception: topical antibiotics are allowed.
• 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.
• 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.
• 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.
• Planned surgery, hospitalizations, dental work, or interventional studies between Screening and last anticipated visit.
• Intolerance of or allergic reaction to EcN or any of the ingredients in SYNB8802 or placebo formulations.
• Dependence on alcohol or drugs of abuse.
• History of or current immunodeficiency disorder including autoimmune disorders and HIV antibody positivity.
• 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).
• Hepatitis C antibody positivity, unless a hepatitis C virus ribonucleic acid test is performed, and the result is negative.
• 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.
• History of bacteremia within 30 days prior to the anticipated first dose of IMP.
• History of inflammatory bowel disease.

Eligibility last updated 2/1/22. Questions regarding updates should be directed to the study team contact.