<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04468958</url>
  </required_header>
  <id_info>
    <org_study_id>SAB-185-101</org_study_id>
    <nct_id>NCT04468958</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability, and Pharmacokinetics of SAB-185 in Healthy Participants</brief_title>
  <official_title>A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study of SAB-185 in Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>SAb Biotherapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Department of Health and Human Services</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
    <collaborator>
      <agency>JPEO, Chemical, Biological, Radiological, and Nuclear Defense (CBRND) Enabling Biotechnologies (EB)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>SAb Biotherapeutics, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute&#xD;
      respiratory syndrome coronavirus 2 (SARS-CoV-2). SAB Biotherapeutics has developed SAB-185,&#xD;
      an Anti-SARS-CoV-2 Human Immunoglobulin Intravenous (transchromosomic [Tc] bovine-derived),&#xD;
      as a potential therapeutic to treat COVID-19. This study will evaluate the safety,&#xD;
      immunogenicity, and pharmacokinetics of SAB-185 in healthy participants.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There were 4 treatment groups and 1 control group. Cohort 1 received 1 dose of SAB-185 at 10&#xD;
      mg/kg per dose. Cohort 2 received 1 dose of SAB-185 at 25 mg/kg, Cohort 3 received 2 doses of&#xD;
      SAB-185 at 25 mg/kg each 7 days apart, and Cohort 4 received 1 dose of SAB-185 at 50 mg/kg&#xD;
      per dose. All the doses were prepared at the site by the pharmacy staff or designee for&#xD;
      delivery to the clinical staff for administration, per the site's SOPs.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 1, 2020</start_date>
  <completion_date type="Actual">December 23, 2020</completion_date>
  <primary_completion_date type="Actual">December 23, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants Having Adverse Events</measure>
    <time_frame>29 Days</time_frame>
    <description>Incidence and severity of other adverse events and severe adverse events (SAE)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants Having Transfusion-Related Adverse Events</measure>
    <time_frame>29 Days</time_frame>
    <description>transfusion-related adverse events</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Having Adverse Events</measure>
    <time_frame>90 Days</time_frame>
    <description>Incidence and severity of adverse events and SAEs from Screening through Study Day 90</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics from screening to day 90</measure>
    <time_frame>90 Days</time_frame>
    <description>SARS-CoV-2 binding (ELISA) and neutralizing (PRNT80) antibody titers from Screening through Study Day 90</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>COVID-19</condition>
  <condition>SARS-CoV2</condition>
  <arm_group>
    <arm_group_label>10mg/kg SAB-185</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10mg/kg SAB-185 in normal (0.9%) saline; concentration 4mg/mL (0.4%)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>25mg/kg SAB-185</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>25mg/kg SAB-185 in normal (0.9%) saline; concentration 20mg/mL (2%)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>25mg/kg SAB-185 x 2 doses</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>25mg/kg SAB-185 in normal (0.9%) saline; concentration 20mg/mL (2%). Cohort 3 will receive a second 25mg/kg dose of SAB-185 7 days (+/-2) after the first treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>50mg/kg SAB-185</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>50mg/kg SAB-185 in normal (0.9%) saline; concentration 20mg/mL (2%)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Normal (0.9%) saline in approximately the same volume as each cohort in the experimental drug arm.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>SAB-185</intervention_name>
    <description>SAB-185 is a purified human immunoglobulin G (hIgG) designed to specifically bind to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) viruses. SAB-185 is purified from the plasma of immunized Tc bovines that were immunized initially (vaccinations 1 and 2) with a plasmid DNA (pDNA) vaccine that expresses wild-type SARS-CoV-2 spike protein, followed by additional immunizations (vaccinations 3 and beyond) with a recombinant spike protein from SARS-CoV-2 produced in insect cells. The purified hIgG is 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.</description>
    <arm_group_label>10mg/kg SAB-185</arm_group_label>
    <arm_group_label>25mg/kg SAB-185</arm_group_label>
    <arm_group_label>25mg/kg SAB-185 x 2 doses</arm_group_label>
    <arm_group_label>50mg/kg SAB-185</arm_group_label>
    <other_name>Anti-SARS-CoV-2 Human Immunoglobulin Intravenous (Tc bovine-derived)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Normal saline</intervention_name>
    <description>Normal (0.9%) saline in approximately the same volume as each cohort in the experimental drug arm.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Subjects must meet all of the following criteria for inclusion:&#xD;
&#xD;
          1. 18-60 years of age&#xD;
&#xD;
          2. Able to understand the study and comply with all study procedures&#xD;
&#xD;
          3. Agrees not to participate in any other trial of an investigational product during the&#xD;
             study period&#xD;
&#xD;
          4. Willing and able to provide written informed consent prior to the start of any study&#xD;
             related activities&#xD;
&#xD;
          5. In good health in the opinion of the site principal investigator as determined by&#xD;
             vital signs, medical history, physical examination and clinical laboratory tests&#xD;
&#xD;
          6. If female, meets at least one of the following reproductive risk criteria&#xD;
&#xD;
               -  Post-menopausal for at least 12 months&#xD;
&#xD;
               -  Use of one or more of the following highly effective contraceptive methods for at&#xD;
                  least 90 days following the last dose of study product: combined estrogen and&#xD;
                  progestogen containing or progestogen-only hormonal contraception, intrauterine&#xD;
                  device (IUD), intrauterine hormone-releasing system, surgical bilateral tubal&#xD;
                  occlusion&#xD;
&#xD;
               -  Vasectomized sole sexual partner who has received medical assessment of the&#xD;
                  surgical success&#xD;
&#xD;
          7. Subjects agree to sexual abstinence (refraining from heterosexual intercourse for at&#xD;
             least 90 days following the last dose of study product) if not using birth control or&#xD;
             condoms for males.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Female subjects with positive pregnancy test, breastfeeding, or planning to become&#xD;
             pregnant/breastfeed during the study period.&#xD;
&#xD;
          2. Treatment or participation in another clinical trial of any other investigational&#xD;
             agent within 30 days prior to enrollment.&#xD;
&#xD;
          3. Use of other drugs that, in the opinion of the investigator, could complicate analysis&#xD;
             of SAB-185.&#xD;
&#xD;
          4. Subjects with the following risk factors:&#xD;
&#xD;
               -  Compromised immune system including confirmed diagnosis of current cancer under&#xD;
                  treatment, inherited deficiencies of the immune system, immune suppressing&#xD;
                  medication, or other conditions causing leukopenia or neutropenia&#xD;
&#xD;
               -  Known autoimmune condition requiring therapy more intensive than intermittent&#xD;
                  non-steroidal anti-inflammatories in the prior 6 months (for example: rheumatoid&#xD;
                  arthritis, lupus, inflammatory bowel disease)&#xD;
&#xD;
               -  Chronic respiratory disease including COPD, emphysema, cystic fibrosis, pulmonary&#xD;
                  hypertension, or other chronic condition that requires the routine use of&#xD;
                  supplemental oxygen&#xD;
&#xD;
               -  Chronic asthma requiring the use of oral steroids or hospitalization in the last&#xD;
                  six months&#xD;
&#xD;
               -  Renal failure or renal insufficiency requiring dialysis&#xD;
&#xD;
               -  Congestive heart failure or significant atherosclerotic disease (coronary artery&#xD;
                  disease or peripheral vascular disease)&#xD;
&#xD;
               -  Hypertension, diabetes, those currently vaping or smoking or with a history of&#xD;
                  chronic smoking, and those with BMI &gt; 35 kg/m2&#xD;
&#xD;
          5. Receipt of pooled immunoglobulin or plasma in past 30 days&#xD;
&#xD;
          6. Any other underlying medical (cardiac, liver, renal, neurological, respiratory) or&#xD;
             psychiatric condition that in the view of the investigator would preclude use of&#xD;
             SAB-185&#xD;
&#xD;
          7. Known IgA deficiency or previous allergic reaction to intravenous immunoglobin&#xD;
             (IVIG)/subcutaneous immunoglobin (SCIG)&#xD;
&#xD;
          8. Positive screening test for hepatitis B virus surface antigen, hepatitis C virus&#xD;
             antibody, or HIV antibody&#xD;
&#xD;
          9. Positive screening test for rheumatoid factor&#xD;
&#xD;
         10. History of COVID-19&#xD;
&#xD;
         11. Positive FDA-authorized screening test for serum SARS-CoV-2 antibody or presence of&#xD;
             SARS-CoV-2 on nasopharyngeal or oropharyngeal swab by FDA-authorized RT-PCR&#xD;
&#xD;
         12. History of allergy, anaphylaxis, or severe reaction to beef products (including milk&#xD;
             and gelatin).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David Hoover, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>ICON GPHS</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Alliance for Multispecialty Research, LLC</name>
      <address>
        <city>Wichita</city>
        <state>Kansas</state>
        <zip>67205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SUNY Upstate Medical University</name>
      <address>
        <city>Syracuse</city>
        <state>New York</state>
        <zip>13210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ICON Early Phase Services</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>July 8, 2020</study_first_submitted>
  <study_first_submitted_qc>July 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 13, 2020</study_first_posted>
  <last_update_submitted>June 28, 2022</last_update_submitted>
  <last_update_submitted_qc>June 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 1, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Immunoglobulins</mesh_term>
    <mesh_term>Immunoglobulins, Intravenous</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Individual participant data that underlie the results reported in the published article, after deidentification (test, tables, figures, and appendices)</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_time_frame>Starting 6 months after publication and ending 36 months following article publication</ipd_time_frame>
    <ipd_access_criteria>Anyone who wishes to access the data.</ipd_access_criteria>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04468958
org study id: SAB-185-101
nct id: NCT04468958
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute
      respiratory syndrome coronavirus 2 (SARS-CoV-2). SAB Biotherapeutics has developed SAB-185,
      an Anti-SARS-CoV-2 Human Immunoglobulin Intravenous (transchromosomic [Tc] bovine-derived),
      as a potential therapeutic to treat COVID-19. This study will evaluate the safety,
      immunogenicity, and pharmacokinetics of SAB-185 in healthy participants.
There were 4 treatment groups and 1 control group. Cohort 1 received 1 dose of SAB-185 at 10
      mg/kg per dose. Cohort 2 received 1 dose of SAB-185 at 25 mg/kg, Cohort 3 received 2 doses of
      SAB-185 at 25 mg/kg each 7 days apart, and Cohort 4 received 1 dose of SAB-185 at 50 mg/kg
      per dose. All the doses were prepared at the site by the pharmacy staff or designee for
      delivery to the clinical staff for administration, per the site's SOPs.
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of Participants Having Adverse Events
time frame: 29 Days
description: Incidence and severity of other adverse events and severe adverse events (SAE)
measure: Number of Participants Having Transfusion-Related Adverse Events
time frame: 29 Days
description: transfusion-related adverse events
measure: Number of Participants Having Adverse Events
time frame: 90 Days
description: Incidence and severity of adverse events and SAEs from Screening through Study Day 90
measure: Pharmacokinetics from screening to day 90
time frame: 90 Days
description: SARS-CoV-2 binding (ELISA) and neutralizing (PRNT80) antibody titers from Screening through Study Day 90
arm group label: 10mg/kg SAB-185
arm group type: Experimental
description: 10mg/kg SAB-185 in normal (0.9%) saline; concentration 4mg/mL (0.4%)
arm group label: 25mg/kg SAB-185
arm group type: Experimental
description: 25mg/kg SAB-185 in normal (0.9%) saline; concentration 20mg/mL (2%)
arm group label: 25mg/kg SAB-185 x 2 doses
arm group type: Experimental
description: 25mg/kg SAB-185 in normal (0.9%) saline; concentration 20mg/mL (2%). Cohort 3 will receive a second 25mg/kg dose of SAB-185 7 days (+/-2) after the first treatment.
arm group label: 50mg/kg SAB-185
arm group type: Experimental
description: 50mg/kg SAB-185 in normal (0.9%) saline; concentration 20mg/mL (2%)
arm group label: Placebo
arm group type: Placebo Comparator
description: Normal (0.9%) saline in approximately the same volume as each cohort in the experimental drug arm.
intervention type: Biological
intervention name: SAB-185
description: SAB-185 is a purified human immunoglobulin G (hIgG) designed to specifically bind to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) viruses. SAB-185 is purified from the plasma of immunized Tc bovines that were immunized initially (vaccinations 1 and 2) with a plasmid DNA (pDNA) vaccine that expresses wild-type SARS-CoV-2 spike protein, followed by additional immunizations (vaccinations 3 and beyond) with a recombinant spike protein from SARS-CoV-2 produced in insect cells. The purified hIgG is 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.
arm group label: 10mg/kg SAB-185
arm group label: 25mg/kg SAB-185
arm group label: 25mg/kg SAB-185 x 2 doses
arm group label: 50mg/kg SAB-185
other name: Anti-SARS-CoV-2 Human Immunoglobulin Intravenous (Tc bovine-derived)
intervention type: Other
intervention name: Normal saline
description: Normal (0.9%) saline in approximately the same volume as each cohort in the experimental drug arm.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: David Hoover, MD
role: Principal Investigator
affiliation: ICON GPHS
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Immunoglobulins
mesh term: Immunoglobulins, Intravenous
sharing ipd: Yes
ipd description: Individual participant data that underlie the results reported in the published article, after deidentification (test, tables, figures, and appendices)
ipd info type: Study Protocol
ipd time frame: Starting 6 months after publication and ending 36 months following article publication
ipd access criteria: Anyone who wishes to access the data.