Safety, Tolerability, and Pharmacokinetics of SAB-301 in Healthy Adults

Study Overview
=================
Brief Summary
-----------------
Background: Middle East Respiratory Syndrome (MERS) is a newly discovered contagious and sometimes fatal respiratory virus. People often get MERS through close contact with an infected person. Scientists are worried that MERS may spread and cause more infections. There are no vaccines or treatments for MERS right now. Researchers think a new therapy called SAB-301 may be able to help. Antibodies are proteins the body makes to attack viruses. SAB-301 is made of antibodies made in cows to fight MERS. The antibodies are collected from plasma, the liquid part of cow blood. Objective: To evaluate the safety and tolerability of SAB-301 in healthy adults. Eligibility: Healthy people ages 18 60 who: Do not have chronic medical problems Do not take any medications (exceptions are acetaminophen, ibuprofen, vitamins, seasonal allergy meds and oral contraception) Do not have allergies to beef products Agree to use two forms of contraception while on study (both men and women) Design: Participants will be screened with: Medical history Physical examination Blood and urine tests Participants will have a return visit. They will have a physical exam and blood tests. They will be randomly assigned to receive either SAB-301 or a placebo which is given by infusion through an arm vein over 1 3 hours. They will be monitored at the clinic for 6 hours after the infusion. They will have additional blood draws. Participants will have 2-hour visits 1, 3, 7, 21, 42, and 90 days after the infusion. At each visit they will be evaluated and have blood and urine tests.

Detailed Description
-----------------
The administration of convalescent plasma or hyperimmune immunoglobulin is often used for treatment of emerging infectious diseases. However, production of large quantities of anti-pathogen human plasma and/or immunoglobulin with high affinity and avidity antibodies currently requires donations by convalescent humans, a process that can limit availability for a number of reasons. One novel alternative source is transchromosomic (Tc) cattle that produce fully human polyclonal IgG (hIgG) de novo and mount a robust antibody immune response after vaccination. This study will evaluate the safety, tolerability, and immunogenicity of SAB-301, a fully human polyclonal anti-MERS IgG collected from transchromosomic cattle. Beginning with a low single-dose, subjects are randomized to receive either SAB-301 or a normal saline control, and evaluated on Study Days 1, 3, 7, 21, 42, and 90. The safety and tolerability is evaluated using symptoms, clinical laboratory tests, pharmacokinetics, and immunogenicity assays. Utilizing a series of stopping rules and a medical monitor, the dose will be escalated as safety and tolerability are established.

Official Title
-----------------
A Phase 1, Randomized Double-Blind, Placebo-Controlled, Single Ascending Dose Safety, Tolerability, and Pharmacokinetics Study of SAB-301 in Healthy Adults

Conditions
-----------------
Middle East Respiratory Syndrome Coronavirus

Intervention / Treatment
-----------------
* Biological: SAB-301
* Other: Normal (9%) Saline


Participation Criteria
=================
Eligibility Criteria
-----------------
INCLUSION CRITERIA: Age greater than or equal to 18 years and less than or equal to 60 years Body mass index (BMI) of 19-32 kg/m(2) Estimated glomerular filtration rate greater than or equal to 70 mL/min at screening, calculated using the CKD-EPI formula Subjects must agree to: Not take any prescription or OTC medications with the exception of acetaminophen, ibuprofen, vitamins, seasonal allergy medications, and/or contraceptive medications for a period 7 days prior to study drug administration (i.e., Day 0) 5. 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. 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 IGIV or human blood products Any chronic medical problem that requires daily oral medications (except Tylenol, ibuprofen, oral contraceptives, vitamins, and seasonal allergy medications). History of cardiovascular disease, cardiomyopathy, heart failure, or unexplained syncope Subjects that have had confirmed MERS Women who are breast-feeding Positive urine or serum pregnancy test Abnormal chemistry panel -defined as any clinically significant baseline Grade 1 or greater toxicity, or any Grade 3 or greater toxicity (regardless of clinical significance) by the toxicity table --evaluating only sodium (Na), potassium (K), serum bicarbonate (total CO2), blood urea nitrogen (BUN), creatinine, glucose, asp (ALT), aspartate aminotransferase (AST), total bilirubin, lactate dehydrogenase (LDH), and estimated glomerular filtration rate (GFR) by the CKD-EPI equation. Abnormal complete blood count (CBC) -defined as any clinically significant baseline Grade 1 or greater toxicity, or any Grade 3 or greater toxicity (regardless of clinical significance) by the toxicity table--evaluating only the WBC (to include absolute neutrophil, lymphocyte, and eosinophil counts), hemoglobin, hematocrit, and platelets. Abnormal urinalysis -defined as any clinically significant baseline Grade 1 or greater toxicity--evaluating only protein, and RBCs Positive rheumatoid factor IgA deficiency (defined as IgA < 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 for 30 days after study drug administration 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
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Cohort 1: 1mg/kg SAB-301 in normal (9%) saline; concentration 1mg/mL (0.1%) | Biological: SAB-301<br>* SAB-301 is a purified human immune globulin G (hIgG) polyclonal antibody designed to specifically bind to the MERS-CoV spike (S) protein, a component of the virion membrane that is responsible for binding of the virus to the host cell. The hIgG is purified from the plasma of immunized transchromosomic (Tc) bovines that were immunized with a recombinant spike protein produced in insect cells. SAB-301 is purified hIgG in a sterile liquid formulated in 10 mM glutamic acid monosodium salt, 262 mM D-sorbitol, 0.05 mg/mL Tween 80, pH 5.5. The drug product will be administered intravenously and will be diluted in saline per the clinical protocol.<br>|
| Placebo Comparator: Placebo<br>Normal (0.9%) saline in approximately the same volume as each cohort in the experimental drug arm. | Other: Normal (9%) Saline<br>* Normal (0.9%) saline in approximately the same volume as each cohort in the experimental drug arm.<br>|
| Experimental: Cohort 2<br>Cohort 2: 2.5 mg/kg SAB-301 in normal (9%) saline; concentration 1mg/mL (0.1%) | Biological: SAB-301<br>* SAB-301 is a purified human immune globulin G (hIgG) polyclonal antibody designed to specifically bind to the MERS-CoV spike (S) protein, a component of the virion membrane that is responsible for binding of the virus to the host cell. The hIgG is purified from the plasma of immunized transchromosomic (Tc) bovines that were immunized with a recombinant spike protein produced in insect cells. SAB-301 is purified hIgG in a sterile liquid formulated in 10 mM glutamic acid monosodium salt, 262 mM D-sorbitol, 0.05 mg/mL Tween 80, pH 5.5. The drug product will be administered intravenously and will be diluted in saline per the clinical protocol.<br>|
| Experimental: Cohort 3<br>Cohort 3: 5mg/kg SAB-301 in normal (9%) saline; concentration 4mg/mL (0.4%) | Biological: SAB-301<br>* SAB-301 is a purified human immune globulin G (hIgG) polyclonal antibody designed to specifically bind to the MERS-CoV spike (S) protein, a component of the virion membrane that is responsible for binding of the virus to the host cell. The hIgG is purified from the plasma of immunized transchromosomic (Tc) bovines that were immunized with a recombinant spike protein produced in insect cells. SAB-301 is purified hIgG in a sterile liquid formulated in 10 mM glutamic acid monosodium salt, 262 mM D-sorbitol, 0.05 mg/mL Tween 80, pH 5.5. The drug product will be administered intravenously and will be diluted in saline per the clinical protocol.<br>|
| Experimental: Cohort 4<br>Cohort 4: 10mg/kg SAB-301 in normal (9%) saline; concentration 4mg/mL (0.4%) | Biological: SAB-301<br>* SAB-301 is a purified human immune globulin G (hIgG) polyclonal antibody designed to specifically bind to the MERS-CoV spike (S) protein, a component of the virion membrane that is responsible for binding of the virus to the host cell. The hIgG is purified from the plasma of immunized transchromosomic (Tc) bovines that were immunized with a recombinant spike protein produced in insect cells. SAB-301 is purified hIgG in a sterile liquid formulated in 10 mM glutamic acid monosodium salt, 262 mM D-sorbitol, 0.05 mg/mL Tween 80, pH 5.5. The drug product will be administered intravenously and will be diluted in saline per the clinical protocol.<br>|
| Experimental: Cohort 5<br>Cohort 5: 20mg/kg SAB-301 in normal (9%) saline; concentration 20mg/mL (2%) | Biological: SAB-301<br>* SAB-301 is a purified human immune globulin G (hIgG) polyclonal antibody designed to specifically bind to the MERS-CoV spike (S) protein, a component of the virion membrane that is responsible for binding of the virus to the host cell. The hIgG is purified from the plasma of immunized transchromosomic (Tc) bovines that were immunized with a recombinant spike protein produced in insect cells. SAB-301 is purified hIgG in a sterile liquid formulated in 10 mM glutamic acid monosodium salt, 262 mM D-sorbitol, 0.05 mg/mL Tween 80, pH 5.5. The drug product will be administered intravenously and will be diluted in saline per the clinical protocol.<br>|
| Experimental: Cohort 6<br>Cohort 6: 50mg/kg SAB-301 in normal (9%) saline; concentration 20mg/mL (2%) | Biological: SAB-301<br>* SAB-301 is a purified human immune globulin G (hIgG) polyclonal antibody designed to specifically bind to the MERS-CoV spike (S) protein, a component of the virion membrane that is responsible for binding of the virus to the host cell. The hIgG is purified from the plasma of immunized transchromosomic (Tc) bovines that were immunized with a recombinant spike protein produced in insect cells. SAB-301 is purified hIgG in a sterile liquid formulated in 10 mM glutamic acid monosodium salt, 262 mM D-sorbitol, 0.05 mg/mL Tween 80, pH 5.5. The drug product will be administered intravenously and will be diluted in saline per the clinical protocol.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Having Adverse Events | Number of participants who experienced an adverse event | 90 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
First in Human, Middle East Respiratory Syndrome (MERS), Tc Bovine-Derived, Transchromosomic Cattle