Clinical trial NCT04471038: Safety, Tolerability, and Pharmacokinetics of SAB-176 in Healthy Participants
Official title: A Phase 1, Randomized Double-Blind, Placebo-Controlled, Single Ascending Dose Safety, Tolerability, and Pharmacokinetics Study of SAB-176 in Healthy Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Influenza Type A
Influenza Type B
Influenza
Lead sponsor: SAb Biotherapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2020-07-14
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: double-blind, randomized, placebo-controlled dose-escalating cohort design
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: This safety and tolerability study of IV SAB-176 consisted of up to 4 single dose levels or cohorts (Cohort 1 through 4) in a double-blind, randomized, placebo-controlled dose-escalating cohort design. Four cohorts of 3 to10 subjects each were administered a single IV dose of SAB-176 or saline placebo. At very low doses, the concern was primarily allergic or T-cell activation/cytokine storm, so small cohort sizes were utilized. As the target dose was approached, the sample size was increased to increase the likelihood of detecting toxicity events.

Eligibility criteria: Inclusion Criteria:

1. Age ≥18 years and ≤60 years
2. Body mass index (BMI) of 19-32 kg/m2
3. 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.
4. Estimated glomerular filtration rate ≥90 mL/min at screening, calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
5. 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:

1. Any history of allergy, anaphylaxis, or severe reaction to beef products (including milk and gelatin)
2. Any history of allergy, anaphylaxis, or severe reaction to IVIg or human blood products
3. 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.
4. History of cardiovascular disease, cardiomyopathy, heart failure, or unexplained syncope
5. Abnormal clinically significant 12-lead electrocardiogram (ECG), per PI discretion
6. 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.
7. Enrollment will be delayed for all patients who have other intercurrent infections (e.g., gastroenteritis, abscess, etc.).
8. Women who are breast-feeding
9. Positive urine or serum pregnancy test
10. Positive urine drug screen (UDS)
11. Clinically significant results, including laboratory results, as determined by study investigator
12. Positive rheumatoid factor
13. IgA deficiency (defined as IgA less than 7 mg/dL)
14. 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
15. Participation in any other research study until the completion of the study
16. Receipt of blood products within 2 months prior to study drug administration (i.e.Day 0)
17. Receipt of any vaccination within 30 days prior to study drug administration (i.e.Day 0)
18. 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

Primary outcomes:
measure: Number of Participants Having Adverse Events
timeFrame: 90 days
Secondary outcomes:
measure: Number of Participants With Anti-SAB-176 Antibodies Elicited by SAB-176
timeFrame: 90 Days
Other outcomes:
Locations:
city: Austin
country: United States
facility: PPD, Phase 1 Clinic
state: Texas
Study officials:
affiliation: PPD Development, LP
name: Rebecca N Wood-Horrall, MD
role: PRINCIPAL_INVESTIGATOR
References: