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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02788188
Other study ID # 160119
Secondary ID 16-I-0119
Status Completed
Phase Phase 1
First received
Last updated
Start date May 28, 2016
Est. completion date April 30, 2018

Study information

Verified date July 2017
Source National Institutes of Health Clinical Center (CC)
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 38
Est. completion date April 30, 2018
Est. primary completion date April 10, 2018
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years to 60 Years
Eligibility - INCLUSION CRITERIA:

1. Age greater than or equal to 18 years and less than or equal to 60 years

2. Body mass index (BMI) of 19-32 kg/m(2)

3. Estimated glomerular filtration rate greater than or equal to 70 mL/min at screening, calculated using the CKD-EPI formula

4. 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:

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 IGIV or human blood products

3. Any chronic medical problem that requires daily oral medications (except Tylenol, ibuprofen, oral contraceptives, vitamins, and seasonal allergy medications).

4. History of cardiovascular disease, cardiomyopathy, heart failure, or unexplained syncope

5. Subjects that have had confirmed MERS

6. Women who are breast-feeding

7. Positive urine or serum pregnancy test

8. 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.

9. 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.

10. Abnormal urinalysis

-defined as any clinically significant baseline Grade 1 or greater toxicity--evaluating only protein, and RBCs

11. Positive rheumatoid factor

12. IgA deficiency (defined as IgA < 7 mg/dL)

13. 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

14. Participation in any other research study for 30 days after study drug administration

15. Receipt of blood products within 2 months prior to study drug administration (i.e. Day 0)

16. Receipt of any vaccination within 30 days prior to study drug administration (i.e. Day 0)

17. 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

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
SAB-301
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.
Other:
Normal (9%) Saline
Normal (0.9%) saline in approximately the same volume as each cohort in the experimental drug arm.

Locations

Country Name City State
United States National Institutes of Health Clinical Center Bethesda Maryland

Sponsors (3)

Lead Sponsor Collaborator
National Institute of Allergy and Infectious Diseases (NIAID) Naval Medical Research Center, SAB Biotherapeutics, Inc

Country where clinical trial is conducted

United States, 

References & Publications (3)

Beigel JH, Voell J, Kumar P, Raviprakash K, Wu H, Jiao JA, Sullivan E, Luke T, Davey RT Jr. Safety and tolerability of a novel, polyclonal human anti-MERS coronavirus antibody produced from transchromosomic cattle: a phase 1 randomised, double-blind, sing — View Citation

Luke T, Wu H, Zhao J, Channappanavar R, Coleman CM, Jiao JA, Matsushita H, Liu Y, Postnikova EN, Ork BL, Glenn G, Flyer D, Defang G, Raviprakash K, Kochel T, Wang J, Nie W, Smith G, Hensley LE, Olinger GG, Kuhn JH, Holbrook MR, Johnson RF, Perlman S, Sullivan E, Frieman MB. Human polyclonal immunoglobulin G from transchromosomic bovines inhibits MERS-CoV in vivo. Sci Transl Med. 2016 Feb 17;8(326):326ra21. doi: 10.1126/scitranslmed.aaf1061. — View Citation

Steinberger BA, Ford SM, Coleman TA. Intravenous immunoglobulin therapy results in post-infusional hyperproteinemia, increased serum viscosity, and pseudohyponatremia. Am J Hematol. 2003 Jun;73(2):97-100. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Number of Participants Having Adverse Events Number of participants who experienced an adverse event 90 days
See also
  Status Clinical Trial Phase
Completed NCT04170829 - A Clinical Trial to Determine the Safety and Immunogenicity of Healthy Candidate MERS-CoV Vaccine (MERS002) Phase 1