Safety, Tolerability, and Pharmacokinetics of SAB-176 in Healthy Participants

Study Overview
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Brief Summary
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Influenza causes substantial morbidity and mortality worldwide despite available antivirals and vaccines. SAB Biotherapeutics, Inc. has developed SAB-176, an anti-influenza human immunoglobulin (transchromosomic [Tc] bovine-derived) intravenous therapeutic to treat past and current strains of Type A Influenza and Type B Influenza. This study will evaluate the safety, tolerability, and pharmacokinetics of SAB-176 in healthy participants.

Official Title
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A Phase 1, Randomized Double-Blind, Placebo-Controlled, Single Ascending Dose Safety, Tolerability, and Pharmacokinetics Study of SAB-176 in Healthy Adults

Conditions
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Influenza Type A, Influenza Type B, Influenza

Intervention / Treatment
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* Biological: SAB-176
* Other: Normal Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years and ≤60 years Body mass index (BMI) of 19-32 kg/m2 Subjects must have values in normal ranges for basic labs (i.e., CBC, PT/INR, Chem-7, and LFTs), unless deemed not clinically significant by the PI. Estimated glomerular filtration rate ≥90 mL/min at screening, calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula Subjects must agree to: Not take any prescription or over-the-counter (OTC) medications with the exception of acetaminophen, ibuprofen, vitamins, seasonal allergy medications, and/or contraceptive medications, or others unless approved by the study investigator, for a period 7 days prior to study drug administration (i.e., Day 0). Use one of the following in order to avoid pregnancy: Females who are able to become pregnant (i.e., are not postmenopausal, have not undergone surgical sterilization, and are sexually active with men) must agree to use at least 2 effective forms of contraception from the date of the subject's signing of the informed consent form through 60 days after the last dose of study drug. At least one of the methods of contraception should be a barrier method. Males who have not undergone surgical sterilization and are sexually active with women must agree to use condoms plus have a partner use at least one additional effective form of contraception from the date of the subject's signing of the informed consent form through 60 days after the last dose of study drug. Neither females or males should donate oocysts or sperm for use in artificial insemination through 60 days after the last dose of study drug. Exclusion Criteria: Any history of allergy, anaphylaxis, or severe reaction to beef products (including milk and gelatin) Any history of allergy, anaphylaxis, or severe reaction to IVIg or human blood products Any chronic medical problem/condition that require medications needed to maintain the subject's health. Exceptions to this restriction can be allowed for minor health conditions that are treated with Tylenol, over-the-counter non-steroidal anti-inflammatories, vitamins, seasonal allergy medications, or oral/transdermal/IUD contraceptives, etc. The study investigator will make a determination to exclude a subject based upon their medical history and the type and frequency of the drug substance. History of cardiovascular disease, cardiomyopathy, heart failure, or unexplained syncope Abnormal clinically significant 12-lead electrocardiogram (ECG), per PI discretion Subjects who have been laboratory confirmed or clinically diagnosed with influenza within seven days prior to infusion (by subject history) will be deferred from infusion. Any subject with signs and symptoms of an active respiratory infection on the day of infusion will be deferred until the infection is cleared in the opinion of the investigator. Subjects that present with an active upper respiratory infection on the day of infusion will be tested with an FDA licensed Influenza A/B Antigen Test. Signs and symptoms constituting an upper respiratory infection include cough, sore throat, or rhinorrhea with or without fever. Enrollment will be delayed for all patients who have other intercurrent infections (e.g., gastroenteritis, abscess, etc.). Women who are breast-feeding Positive urine or serum pregnancy test Positive urine drug screen (UDS) Clinically significant results, including laboratory results, as determined by study investigator Positive rheumatoid factor IgA deficiency (defined as IgA less than 7 mg/dL) Participation in another research study with receipt of any investigational drug within 5 half-lives or 30 days, whichever is longer, prior to study drug administration (i.e., Day 0) and until completion of the study Participation in any other research study until the completion of the study Receipt of blood products within 2 months prior to study drug administration (i.e.Day 0) Receipt of any vaccination within 30 days prior to study drug administration (i.e.Day 0) Any acute or chronic condition that, in the opinion of the Investigator, would limit the subject's ability to complete and/or participate in this clinical study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>1 mg/mL SAB-176 in normal (0.9%) Saline; concentration 1 mg/mL (0.1%) | Biological: SAB-176<br>* Anti-Influenza Human Immunoglobulin Intravenous (Tc bovine derived)<br>|
| Experimental: Cohort 2<br>10 mg/kgSAB-176 in normal (0.9%) Saline; concentration 4 mg/mL (0.4%) | Biological: SAB-176<br>* Anti-Influenza Human Immunoglobulin Intravenous (Tc bovine derived)<br>|
| Experimental: Cohort 3<br>25 mg/kgSAB-176 in normal (0.9%) Saline; concentration 20 mg/mL (2.0%) | Biological: SAB-176<br>* Anti-Influenza Human Immunoglobulin Intravenous (Tc bovine derived)<br>|
| Experimental: Cohort 4<br>50 mg/kg SAB-176 in normal (0.9%) Saline; concentration 20 mg/mL (2.0%) | Biological: SAB-176<br>* Anti-Influenza Human Immunoglobulin Intravenous (Tc bovine derived)<br>|
| Placebo Comparator: Cohort 5<br>Normal (0.9%) saline in approximately the same volume as each cohort in the experimental drug arm. | Other: Normal Saline<br>* Normal (0.9%) saline in approximately the same volume as each cohort in the experimental drug arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants having adverse events | Incidence and severity of other adverse events and severe adverse events (SAE) | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of Serum SAB-176 Titers | Measurement of Influenza antibody titers in serum using hemagglutination Inhibition (HAI) assay screening through Study Day 90 | 90 Days | 
| Assessment of the PD of SAB-176 administered Intravenously | Influenza antibody titers in serum using hemagglutination Inhibition (HAI) assay screening through Study Day 90 | 90 Days | 
| Ability of serum SAB-176 levels to neutralize Influenza to day 90 | Serum levels of SAB-176 using microneutralization (MN) assay through day 90 | 90 Days | 
| Immune response elicited by SAB-176 | Measurement of rheumatoid factor through day 90 | 90 Days | 
| Concentration of subject anti-SAB-176 antibodies elicited by SAB-176 | Measurement of anti-SAB-176 antibodies through day 90 | 90 Days |