Safety and Tolerability of FB-001 in Healthy Adult Volunteers and Adult Subjects With Enteric Hyperoxaluria

Launched by FEDERATION BIO INC. · Dec 6, 2022

Keywords

ClinConnect Summary

This clinical trial is investigating a new treatment called FB-001, which is being tested for safety and how well it can be tolerated by both healthy adults and adults with a condition known as enteric hyperoxaluria. This condition involves the body absorbing too much oxalate from food, which can lead to kidney stones. The trial is divided into two parts: the first part includes healthy volunteers aged 18 to 50, while the second part focuses on adults aged 18 to 74 who have been diagnosed with enteric hyperoxaluria.

To participate, individuals must meet certain criteria. For healthy volunteers, they need to have a normal weight, no significant health issues, and specific urinary oxalate levels. For those with enteric hyperoxaluria, they also need to be within a certain age range and have high urinary oxalate levels. Participants in the trial will receive the study drug and undergo regular health check-ups, including tests on their blood, urine, and stool. It’s important to note that participants should be ready to follow specific dietary guidelines and treatment procedures throughout the study. Overall, this trial aims to see if FB-001 could be a safe and effective option for managing enteric hyperoxaluria.

Gender

ALL

Eligibility criteria

• Part 1 Key Inclusion Criteria:
• • 1. ≥ 18 to ≤ 50 years.
• • 2. Willing to participate and sign the informed consent form.
• • 3. Available for and agree to comply with all study requirements, including duration of stay at the clinical pharmacology unit, adherence to diet control, study drug administration, follow-up visits, and collection of stool, urine, and blood.
• • 4. Normal clinical laboratory test results which are not considered to be clinically significant by the Investigator at Screening (including an estimated glomerular filtration rate \[eGFR\] \>60 mL/min/1.73 m2 calculated using the Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] equation).
• • 5. Body mass index (BMI) 18 to 35 kg/m2.
• • 6. Volunteers must have 24-hour urinary oxalate \<45 mg.
• Part 1 Key Exclusion Criteria:
• • 1. Presence or history of any significant cardiovascular, gastrointestinal, hepatic, renal, pulmonary, hematologic, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease, as determined by the Investigator.
• • 2. Presence or history of any condition or procedure (including surgery) known to interfere with the absorption, distribution, metabolism, or excretion of medicines.
• • 3. Participation in any study of an investigational product, biologic, device, or other agent within 30 days prior to admission on Day -7 or unwilling to forego other forms of investigational treatment during this study.
• • 4. Major surgery or an inpatient hospital stay within 3 months prior to admission on Day -7.
• • 5. A positive serologic test for infection with human immunodeficiency virus, hepatitis C virus, or hepatitis B virus.
• • 6. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin \>1.5 × upper limit of normal (ULN).
• • 7. Hemoglobin A1c (HbA1c) ≥6.5 percent.
• • 8. Hyperthyroidism or hypothyroidism as defined by thyroid-stimulating hormone (TSH) levels outside the normal reference range.
• • 9. History of QT prolongation or dysrhythmia or a family history of prolonged QT interval or sudden death.
• • 10. Use of prescription drugs (except for hormonal contraceptives) including cisapride, pimozide, astemizole, terfenadine, ergotamine, or dihydroergotamine within 4 weeks prior to Screening and unable or unwilling to refrain from such use through the end of study visit.
• • 11. Use of any herbal or over-the-counter medications, probiotic products, or vitamin supplements, including vitamin C, within 14 days prior to first administration of study drug through the end of the Confinement Period.
• • 12. Planned procedures that may require antibiotics between Screening and the end of study visit.
• • 13. Use of antibiotic treatment up to 4 weeks prior to or during Screening, or between Screening and admission (Day -7), or a history of recurrent infections requiring antibiotics.
• • 14. A known hypersensitivity to MiraLax, clarithromycin, erythromycin, any of the macrolide antibiotics, metronidazole or other nitroimidazole derivatives.
• • 15. A history of kidney stones.
• • 16. Unwilling to comply with all study procedures and assessments, including the High Oxalate Low Calcium (HOLC) diet and the pretreatment regimen, which includes antibiotics.
• Part 2 Key Inclusion Criteria:
• • 1. ≥ 18 to ≤ 74 years.
• • 2. Willing to participate and sign the informed consent form.
• • 3. Available for and agree to comply with all study requirements, including study drug administration, follow-up visits, and collection of stool, urine, and blood.
• • 4. Body Mass Index (BMI) 18 to 40 kg/m2.
• • 5. Enteric hyperoxaluria diagnosis as indicated by 24-hour urinary oxalate levels of ≥50 mg at Screening. Enteric hyperoxaluria is defined as increased gastrointestinal oxalate absorption in the context of fat malabsorption and/or increased intestinal permeability to oxalate caused by gastrointestinal disorders.
• • 6. Screening laboratory evaluations (eg, chemistry panel, complete blood count with differential, prothrombin time/activated partial thromboplastin time, urinalysis) and a 12-lead ECG that are within normal limits or judged to be not clinically significant by the Investigator.
• • 7. Patients on concomitant medication for management of kidney stone risk factors (eg, calcium supplements, thiazide diuretics, allopurinol, and alkali therapy) must be on stable dose regimen for at least 8 weeks prior to Screening, with no changes in dosing (dose level or dosing frequency) anticipated during the study Treatment Period.
• Part 2 Key Exclusion Criteria:
• • 1. Presence or history of any significant cardiovascular, gastrointestinal, hepatic, renal, pulmonary, hematologic, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease, as determined by the Investigator.
• • 2. Presence or history of any condition or procedure (including surgery) known to interfere with the absorption, distribution, metabolism, or excretion of medicines.
• • 3. Participation in any study of an investigational product, biologic, device, or other agent within 30 days prior to Visit 1 (Day -7) or are not willing to forego other forms of investigational treatment during this study.
• • 4. Major surgery or an inpatient hospital stay within 3 months prior to Visit 1 (Day -7).
• • 5. Uncontrolled hypertension with systolic blood pressure \>160 mmHg and diastolic blood pressure \>100 mmHg.
• • 6. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2 × upper limit of normal (ULN) or total bilirubin \>1 × ULN at Screening unless the patient has known Gilbert's syndrome.
• • 7. Hemoglobin A1c (HbA1c) ≥6.5 percent.
• • 8. Hyperthyroidism or hypothyroidism as defined by thyroid stimulating hormone (TSH) levels outside the normal reference range.
• • 9. History of QT prolongation or dysrhythmia, or a family history of prolonged QT interval or sudden death.
• • 10. Estimated glomerular filtration rate (eGFR) \<45 mL/min/1.73 m2 calculated using the CKD-EPI equation.
• • 11. Loose or liquid stools (Bristol Stool Scale Type 6 or 7) within 1 week prior to or during Screening.
• • 12. Consumption of any herbal medications, probiotic products, or vitamin supplements, including vitamin C, within 14 days prior to first administration of study drug through the end of the Treatment Period.
• • 13. Chronic therapy with high doses of systemic steroids (\>10 mg/day prednisone or equivalent daily) or intensification of existing immunosuppressant or immunomodulatory therapy for treatment of an acute disease flare within 4 weeks prior to or during Screening.
• • 14. Planned procedures that may require antibiotics between Screening and the end of study visit.
• • 15. Use of antibiotic treatment up to 4 weeks prior to or during Screening, or between Screening and Visit 1 (Day -7), or a history of recurrent infections requiring antibiotics.
• • 16. A known hypersensitivity to MiraLax, clarithromycin, erythromycin, any of the macrolide antibiotics, metronidazole, or other nitroimidazole derivatives.
• • 17. Unable or unwilling to discontinue use of cisapride, pimozide, astemizole, terfenadine, ergotamine, or dihydroergotamine from Visit 1 (Day -7) through the end of study visit.
• • 18. A known genetic, congenital, or other known causes of kidney stones (eg, primary hyperoxaluria, cystinuria, primary hyperparathyroidism, or medullary sponge kidney).
• • 19. A history of Roux-en-Y gastric bypass or other bariatric surgery procedures within 6 months prior to Screening.
• • 20. Inflammatory bowel disease that is clinically unstable or have a change in medication to control disease activity within 4 weeks prior to Screening.
• • 21. Unwilling to comply with all study procedures and assessments, including need for pretreatment regimen which includes antibiotics.

Trial Officials