Influenza, Influenza Type A, Influenza Type B
Conditions
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.
Interventions
BIOLOGICALSAB-176
Anti-Influenza Human Immunoglobulin Intravenous (Tc bovine derived)
OTHERNormal Saline
Normal (0.9%) saline in approximately the same volume as each cohort in the experimental drug arm
Sponsors
SAb Biotherapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
double-blind, randomized, placebo-controlled dose-escalating cohort design
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Having Adverse Events | 90 days | Incidence and severity of other adverse events and severe adverse events (SAE) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Anti-SAB-176 Antibodies Elicited by SAB-176 | 90 Days | Number of subjects showing antidrug antibodies to SAB-176 through day 90 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 1 mg/mL SAB-176 in normal (0.9%) Saline; concentration 1 mg/mL (0.1%)
SAB-176: Anti-Influenza Human Immunoglobulin Intravenous (Tc bovine derived) | 2 |
| Cohort 2 10 mg/kgSAB-176 in normal (0.9%) Saline; concentration 4 mg/mL (0.4%)
SAB-176: Anti-Influenza Human Immunoglobulin Intravenous (Tc bovine derived) | 4 |
| Cohort 3 25 mg/kgSAB-176 in normal (0.9%) Saline; concentration 20 mg/mL (2.0%)
SAB-176: Anti-Influenza Human Immunoglobulin Intravenous (Tc bovine derived) | 6 |
| Cohort 4 50 mg/kg SAB-176 in normal (0.9%) Saline; concentration 20 mg/mL (2.0%)
SAB-176: Anti-Influenza Human Immunoglobulin Intravenous (Tc bovine derived) | 8 |
| Cohort 5 Normal (0.9%) saline in approximately the same volume as each cohort in the experimental drug arm.
Normal Saline: Normal (0.9%) saline in approximately the same volume as each cohort in the experimental drug arm | 7 |
| Total | 27 |
Baseline characteristics
| Characteristic | Cohort 2 | Total | Cohort 5 | Cohort 4 | Cohort 3 | Cohort 1 |
|---|---|---|---|---|---|---|
| Age, Customized | 43.3 years STANDARD_DEVIATION 14.41 | 36.9 years STANDARD_DEVIATION 10.02 | 35.7 years STANDARD_DEVIATION 9.95 | 34.1 years STANDARD_DEVIATION 7.72 | 40.5 years STANDARD_DEVIATION 10.07 | 29.0 years STANDARD_DEVIATION 5.66 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 15 Participants | 4 Participants | 4 Participants | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 12 Participants | 3 Participants | 4 Participants | 3 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 5 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 21 Participants | 7 Participants | 7 Participants | 4 Participants | 1 Participants |
| Screening BMI | 23.95 kg/m^2 STANDARD_DEVIATION 4.779 | 27.13 kg/m^2 STANDARD_DEVIATION 3.689 | 26.13 kg/m^2 STANDARD_DEVIATION 4.389 | 28.58 kg/m^2 STANDARD_DEVIATION 2.23 | 27.95 kg/m^2 STANDARD_DEVIATION 3.5 | 28.70 kg/m^2 STANDARD_DEVIATION 0.707 |
| Screening Weight (kg) | 62.68 kg STANDARD_DEVIATION 11.054 | 78.13 kg STANDARD_DEVIATION 15.242 | 72.67 kg STANDARD_DEVIATION 11.226 | 85.26 kg STANDARD_DEVIATION 10.859 | 85.95 kg STANDARD_DEVIATION 18.888 | 76.10 kg STANDARD_DEVIATION 18.95 |
| Sex: Female, Male Female | 3 Participants | 13 Participants | 4 Participants | 2 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 14 Participants | 3 Participants | 6 Participants | 4 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 4 | 0 / 6 | 0 / 8 | 0 / 7 |
| other Total, other adverse events | 0 / 2 | 1 / 4 | 1 / 6 | 1 / 8 | 2 / 7 |
| serious Total, serious adverse events | 0 / 2 | 0 / 4 | 0 / 6 | 0 / 8 | 0 / 7 |
Outcome results
Primary
Number of Participants Having Adverse Events
Incidence and severity of other adverse events and severe adverse events (SAE)
Time frame: 90 days
Population: At each level of subject summarization, a subject is counted once if the subject reported one or more events.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 | Number of Participants Having Adverse Events | 0 Participants |
| Cohort 2 | Number of Participants Having Adverse Events | 1 Participants |
| Cohort 3 | Number of Participants Having Adverse Events | 1 Participants |
| Cohort 4 | Number of Participants Having Adverse Events | 1 Participants |
| Cohort 5 | Number of Participants Having Adverse Events | 2 Participants |
Secondary
Number of Participants With Anti-SAB-176 Antibodies Elicited by SAB-176
Number of subjects showing antidrug antibodies to SAB-176 through day 90
Time frame: 90 Days
Population: Subjects who received SAB-176 or placebo with 1 or more samples obtained after SAB-176 or placebo administration.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 | Number of Participants With Anti-SAB-176 Antibodies Elicited by SAB-176 | 0 Participants |
| Cohort 2 | Number of Participants With Anti-SAB-176 Antibodies Elicited by SAB-176 | 0 Participants |
| Cohort 3 | Number of Participants With Anti-SAB-176 Antibodies Elicited by SAB-176 | 2 Participants |
| Cohort 4 | Number of Participants With Anti-SAB-176 Antibodies Elicited by SAB-176 | 1 Participants |