Middle East Respiratory Syndrome CoronavirusPhase 1NCT02788188
Safety, Tolerability, and Pharmacokinetics of SAB-301 in Healthy Adults
A Phase 1 study testing SAB-301 and Normal (9%) Saline in people with Middle East Respiratory Syndrome Coronavirus, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Middle East Respiratory Syndrome Coronavirus
- What is being tested?
- SAB-301 and Normal (9%) Saline
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- 28 May 2016to 30 Apr 2018
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 21Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: A Phase 1, Randomized Double-Blind, Placebo-Controlled, Single Ascending Dose Safety, Tolerability, and Pharmacokinetics Study of SAB-301 in Healthy Adults
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.
Read more
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.
Read the 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.
- Being tested
- SAB-301, Normal (9%) Saline
- Keywords
- First in Human, Middle East Respiratory Syndrome (MERS), Tc Bovine-Derived, Transchromosomic Cattle
- Medical subject headings
- Coronavirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SAB-301Biological
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.
Normal (9%) SalineOther
Normal (0.9%) saline in approximately the same volume as each cohort in the experimental drug arm.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Cohort 1: 1mg/kg SAB-301 in normal (9%) saline; concentration 1mg/mL (0.1%) Receives: Biological: SAB-301 |
| Placebo | Placebo comparator | Normal (0.9%) saline in approximately the same volume as each cohort in the experimental drug arm. Receives: Other: Normal (9%) Saline |
| Cohort 2 | Experimental | Cohort 2: 2.5 mg/kg SAB-301 in normal (9%) saline; concentration 1mg/mL (0.1%) Receives: Biological: SAB-301 |
| Cohort 3 | Experimental | Cohort 3: 5mg/kg SAB-301 in normal (9%) saline; concentration 4mg/mL (0.4%) Receives: Biological: SAB-301 |
| Cohort 4 | Experimental | Cohort 4: 10mg/kg SAB-301 in normal (9%) saline; concentration 4mg/mL (0.4%) Receives: Biological: SAB-301 |
| Cohort 5 | Experimental | Cohort 5: 20mg/kg SAB-301 in normal (9%) saline; concentration 20mg/mL (2%) Receives: Biological: SAB-301 |
| Cohort 6 | Experimental | Cohort 6: 50mg/kg SAB-301 in normal (9%) saline; concentration 20mg/mL (2%) Receives: Biological: SAB-301 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Having Adverse Events
Number of participants who experienced an adverse event
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2016 (estimated)
- Study start28 May 2016
- Primary completion10 Apr 2018
- Study completion30 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Middle East Respiratory Syndrome CoronavirusStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Naval Medical Research Center, SAb Biotherapeutics, Inc.
- Responsible party
- Sponsor
- Investigators
- Richard T Davey, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02788188
- Sponsor's protocol ID
- 160119
- Other IDs
- 16-I-0119
- Status last verified
- Jul 2017
- First submitted
- 28 May 2016
- Last updated
- 12 Jun 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 26888429Steinberger 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. doi: 10.1002/ajh.10325.
PubMed 12749010Beigel 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, single-dose-escalation study. Lancet Infect Dis. 2018 Apr;18(4):410-418. doi: 10.1016/S1473-3099(18)30002-1. Epub 2018 Jan 9.
PubMed 29329957
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Randomized Double-Blind, Placebo-Controlled, Single Ascending Dose Safety, Tolerability, and Pharmacokinetics Study of SAB-301 in Healthy Adults
- ClinicalTrials.gov ID
- NCT02788188
- Acronym / sponsor ID
- 160119
- Keywords
- First in Human, Middle East Respiratory Syndrome (MERS), Tc Bovine-Derived, Transchromosomic Cattle
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Naval Medical Research Center, SAb Biotherapeutics, Inc.
- Study start
- 28 May 2016
- Primary completion
- 10 Apr 2018 (actual)
- Study completion
- 30 Apr 2018 (actual)
- First posted
- 2 Jun 2016 (estimated)
- Results
- Posted 12 Jun 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Biological: SAB-301Cohort 1: 1mg/kg SAB-301 in normal (9%) saline; concentration 1mg/mL (0.1%) |
| Placebo | Placebo comparator | Other: Normal (9%) SalineNormal (0.9%) saline in approximately the same volume as each cohort in the experimental drug arm. |
| Cohort 2 | Experimental | Biological: SAB-301Cohort 2: 2.5 mg/kg SAB-301 in normal (9%) saline; concentration 1mg/mL (0.1%) |
| Cohort 3 | Experimental | Biological: SAB-301Cohort 3: 5mg/kg SAB-301 in normal (9%) saline; concentration 4mg/mL (0.4%) |
| Cohort 4 | Experimental | Biological: SAB-301Cohort 4: 10mg/kg SAB-301 in normal (9%) saline; concentration 4mg/mL (0.4%) |
| Cohort 5 | Experimental | Biological: SAB-301Cohort 5: 20mg/kg SAB-301 in normal (9%) saline; concentration 20mg/mL (2%) |
| Cohort 6 | Experimental | Biological: SAB-301Cohort 6: 50mg/kg SAB-301 in normal (9%) saline; concentration 20mg/mL (2%) |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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)
- 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.
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SAB-301SAB-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. | Biological | Cohort 1, Cohort 2, Cohort 3, Cohort 4, Cohort 5, Cohort 6 |
| Normal (9%) SalineNormal (0.9%) saline in approximately the same volume as each cohort in the experimental drug arm. | Other | Placebo |
Primary outcome
Number of Participants Having Adverse Events
Time frame: 90 days
Number of participants who experienced an adverse event
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 26888429Luke 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.
- Background: PubMed 12749010Steinberger 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. doi: 10.1002/ajh.10325.
- Results publication: PubMed 29329957Beigel 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, single-dose-escalation study. Lancet Infect Dis. 2018 Apr;18(4):410-418. doi: 10.1016/S1473-3099(18)30002-1. Epub 2018 Jan 9.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard T Davey, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SAB-301 and Normal (9%) Saline in people with Middle East Respiratory Syndrome Coronavirus, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jun 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Having Adverse Events (time frame: 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02788188, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2018.