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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02788188
Recruitment Status : Active, not recruiting
First Posted : June 2, 2016
Last Update Posted : October 19, 2017
Sponsor:
Information provided by (Responsible Party):

Study Description
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.


Condition or disease Intervention/treatment Phase
Middle East Respiratory Syndrome Coronavirus Biological: SAB-301 Other: Normal (9%) Saline Phase 1

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.


Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 43 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 1, Randomized Double-Blind, Placebo-Controlled, Single Ascending Dose Safety, Tolerability, and Pharmacokinetics Study of SAB-301 in Healthy Adults
Study Start Date : May 28, 2016
Estimated Primary Completion Date : April 10, 2018
Estimated Study Completion Date : April 30, 2018

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: A
Cohort 1: 1mg/kg SAB-301 in normal (9%) saline; concentration 1mg/mL (0.1%)Cohort 2: 2.5 mg/kg SAB-301 in normal (9%) saline; concentration 1mg/mL (0.1%)Cohort 3: 5mg/kg SAB-301 in normal (9%) saline; concentration 4mg/mL (0.4%) Cohort 4: 10mg/kg SAB-301 in normal (9%) saline; concentration 4mg/mL (0.4%) Cohort 5: 20mg/kg SAB-301 in normal (9%) saline; concentration 20mg/mL (2%) Cohort 6: 50mg/kg SAB-301 in normal (9%) saline; concentration 20mg/mL (2%)
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.
Placebo Comparator: B
Normal (0.9%) saline in approximately the same volume as each cohort in the experimental drug arm.
Other: Normal (9%) Saline
Normal (0.9%) saline in approximately the same volume as each cohort in the experimental drug arm.


Outcome Measures

Primary Outcome Measures :
  1. Type and frequency of adverse events [ Time Frame: During and up to 90 (+/-) days after study drug infusion ]

Secondary Outcome Measures :
  1. Pharmacokinetic profile [ Time Frame: 90 (+/-) days after study drug infusion ]
  2. Frequency and concentrations of antibodies caused by SAB-301 [ Time Frame: 90 (+/-) days after study drug infusion ]

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria
  • 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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02788188


Locations
United States, Maryland
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Principal Investigator: Richard T Davey, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT02788188     History of Changes
Other Study ID Numbers: 160119
16-I-0119
First Posted: June 2, 2016    Key Record Dates
Last Update Posted: October 19, 2017
Last Verified: July 12, 2017

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):
First in Human
Middle East Respiratory Syndrome (MERS)
Tc Bovine-Derived
Transchromosomic Cattle

Additional relevant MeSH terms:
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases