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

NCT ID: NCT05650112

Last Updated: 2023-01-25

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-16
• Study Completion Date: 2024-08-31

Brief Summary

This Phase 1, first-in-human, randomized, double-blinded, placebo controlled study is evaluating FB-001 in healthy volunteers (Part 1) and participants diagnosed with enteric hyperoxaluria (Part 2). Eligible participants receive investigational product and undergo safety monitoring, evaluations and subsequent follow-up after investigational product administration.

Detailed Description

This study is evaluating the safety, tolerability and microbial kinetics of FB-001 within the following 2 study parts:

Part 1 is an inpatient, placebo-controlled, study in 32 healthy volunteer male and female participants (16 treated: 16 placebo) for 10 days of dosing consisting of a loading dose of 1 × 10^12 viable cells administered orally on Day 1 and Day 2 and a dose of 1 × 10^11 viable cells administered orally on Day 3 to Day 10.

Part 2 is an outpatient open label study in up to 16 adult male and female participants with enteric hyperoxaluria, defined as increased gastrointestinal oxalate absorption in the context of fat malabsorption and/or increased intestinal permeability to oxalate caused by gastrointestinal disorders. Participants will receive FB-001 for 10 days consisting of a loading dose of 1 × 10^12 viable cells administered orally on Day 1 and Day 2 and a dose of 1 × 10^11 viable cells administered orally on Day 3 to Day 10.

Conditions

Healthy; Enteric Hyperoxaluria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

FB-001 Healthy Volunteer

Healthy volunteer participants in Part 1 receive FB-001 (1 x 10\^12 viable cells) orally on Day 1 and Day 2 and FB-001 (1 x 10\^11 viable cells) orally on Days 3 to 10.

Group Type: EXPERIMENTAL

FB-001

Intervention Type: BIOLOGICAL

FB-001 is formulated as a powder in capsule intended for oral administration

Placebo

Healthy volunteer participants receive placebo once a day, orally, for 10 days in Part 1.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

In order to maintain study blinding, matching placebo in identical packaging is manufactured using an inactive powder in capsule

FB-001 Enteric Hyperoxaluria

Enteric hyperoxaluria participants in Part 2 receive FB-001 (1 x 10\^12 viable cells) orally on Day 1 and Day 2 and FB-001 (1 x 10\^11 viable cells) orally on Days 3 to 10.

Group Type: EXPERIMENTAL

FB-001

Intervention Type: BIOLOGICAL

FB-001 is formulated as a powder in capsule intended for oral administration

Interventions

FB-001

FB-001 is formulated as a powder in capsule intended for oral administration

Intervention Type: BIOLOGICAL

Placebo

In order to maintain study blinding, matching placebo in identical packaging is manufactured using an inactive powder in capsule

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

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.

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.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 74 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Federation Bio Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andreas Grauer, MD

Role: STUDY_DIRECTOR

Chief Medical Officer

Locations

Medpace Clinical Pharmacology Unit

Cincinnati, Ohio, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Marguerite Prior, PhD

Role: CONTACT

mprior@federation.bio

650-434-8282

Joumana Zeid

Role: CONTACT

jzeid@federation.bio

Facility Contacts

Leela Vrishabhendra, MD

Role: primary

L.Vrishabhendra@medpace.com

513-366-3221 ext. 12967

Other Identifiers

FB-001-101

Identifier Type: -

Identifier Source: org_study_id