Adaptive COVID-19 Treatment Trial (ACTT)

COVID-19 Clinical Trial

Official title:

A Multicenter, Adaptive, Randomized Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Adults

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04280705
• Other study ID #: 20-0006
• Status: Completed
• Phase: Phase 3
• Start date: February 21, 2020
• Est. completion date: May 21, 2020

Study information

• Verified date: April 2020
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is an adaptive, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. The study is a multicenter trial that will be conducted in up to approximately 100 sites globally. The study will compare different investigational therapeutic agents to a control arm. There will be interim monitoring to introduce new arms and allow early stopping for futility, efficacy, or safety. If one therapy proves to be efficacious, then this treatment may become the control arm for comparison(s) with new experimental treatment(s). Any such change would be accompanied by an updated sample size. Because background standards of supportive care may evolve/improve over time as more is learned about successful management of COVID-19, comparisons of safety and efficacy will be based on data from concurrently randomized subjects. An independent Data and Safety Monitoring Board (DSMB) will actively monitor interim data to make recommendations about early study closure or changes to study arms. To evaluate the clinical efficacy, as assessed by time to recovery, of different investigational therapeutics as compared to the control arm.

Description:

This study is an adaptive, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. The study is a multicenter trial that will be conducted in up to approximately 100 sites globally. The study will compare different investigational therapeutic agents to a control arm. There will be interim monitoring to introduce new arms and allow early stopping for futility, efficacy, or safety. If one therapy proves to be efficacious, then this treatment may become the control arm for comparison(s) with new experimental treatment(s). Any such change would be accompanied by an updated sample size. Because background standards of supportive care may evolve/improve over time as more is learned about successful management of COVID-19, comparisons of safety and efficacy will be based on data from concurrently randomized subjects. An independent Data and Safety Monitoring Board (DSMB) will actively monitor interim data to make recommendations about early study closure or changes to study arms. The initial sample size is projected to be 572 subjects to achieve 400 subjects with a "recovered" status (per the primary objective). The primary analysis will be based on those subjects enrolled in order to 400 recoveries. An additional analysis of the moderate severity subgroup (those with baseline status of "Hospitalized, requiring supplemental oxygen" or "Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care") is also of public health importance. Hence, enrollment will be permitted until the date of April 20, 2020 to ensure 400 recoveries and provide additional data about this important subgroup. With recent enrollment rates, the total sample size may be 600 to over 800. Subjects will be assessed daily while hospitalized. If the subjects are discharged from the hospital, they will have a study visit at Days 15, 22, and 29 as an outpatient. For discharged subjects, it is preferred that the Day 15 and 29 visits are in person to obtain safety laboratory tests and OP swab and blood (serum only) samples for secondary research as well as clinical outcome data. However, infection control or other restrictions may limit the ability of the subject to return to the clinic. In this case, Day 15 and 29 visits may be conducted by phone, and only clinical data will be obtained. The Day 22 visit does not have laboratory tests or collection of samples and may also be conducted by phone. All subjects will undergo a series of efficacy, safety, and laboratory assessments. Safety laboratory tests and blood (serum and plasma) research samples and oropharyngeal (OP) swabs will be obtained on Days 1 (prior to infusion) and Days 3, 5, 8, and 11 (while hospitalized). OP swabs and blood (serum only) plus safety laboratory tests will be collected on Day 15 and 29 (if the subject attends an in-person visit or are still hospitalized). The primary outcome is time to recovery by Day 29. A key secondary outcome evaluates treatment-related improvements in the 8-point ordinal scale at Day 15. As little is known about the clinical course of COVID-19, a pilot study will be used for a blinded sample size reassessment. Contacts: 20-0006 Central Contact Telephone: 1 (301) 7617948 Email: DMIDClinicalTrials@niaid.nih.gov

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1062
• Est. completion date: May 21, 2020
• Est. primary completion date: May 21, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

1. Admitted to a hospital with symptoms suggestive of COVID-19 infection.

2. Subject (or legally authorized representative) provides informed consent prior to initiation of any study procedures.

3. Subject (or legally authorized representative) understands and agrees to comply with planned study procedures.

4. Male or non-pregnant female adult > / = 18 years of age at time of enrollment.

5. Has laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR) or other commercial or public health assay in any specimen, as

documented by either or the following:

1. PCR positive in sample collected < 72 hours prior to randomization; OR

Exclusion Criteria:

2. PCR positive in sample collected >/= 72 hours prior to randomization, documented inability to obtain a repeat sample (e.g. due to lack of testing supplies, limited testing capacity, results taking >24 hours, etc.) AND progressive disease suggestive of ongoing SARS-CoV-2 infection.

6. Illness of any duration, and at least one of the following:

1. Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), OR

2. SpO2 < / = 94% on room air, OR

3. Requiring supplemental oxygen, OR

4. Requiring mechanical ventilation.

7. Women of childbearing potential must agree to either abstinence or use at least one primary form of contraception not including hormonal contraception from the time of screening through Day 29.

8. Agrees to not participate in another clinical trial for the treatment of COVID-19 or SARS-CoV-2 through Day 29.

Exclusion Criteria:

1. Alanine Transaminase (ALT) or Aspartate Transaminase (AST) > 5 times the upper limit of normal.

2. Estimated glomerular filtration rate (eGFR) < 30 ml/min (including patients receiving hemodialysis or hemofiltration).

3. Pregnancy or breast feeding.

4. Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 72 hours.

5. Allergy to any study medication.

Related Conditions & MeSH terms

• COVID-19

Intervention

Other:
• Placebo
The supplied placebo lyophilized formulation is identical in physical appearance to the active lyophilized formulation and contains the same inactive ingredients. Alternatively, a placebo of normal saline of equal volume may be given if there are limitations on matching placebo supplies.

Drug:
• Remdesivir
Drug Remdesivir is a single diastereomer monophosphoramidate prodrug designed for the intracellular delivery of a modified adenine nucleoside analog GS-441524. In addition to the active ingredient, the lyophilized formulation of Remdesivir contains the following inactive ingredients: water for injection, sulfobutylether beta-cyclodextrin sodium (SBECD), and hydrochloric acid and/or sodium hydroxide.

Locations

Country	Name	City	State
Denmark	University of Copenhagen - Centre of Excellence for Health, Immunity and Infections (CHIP) - Department of Infectious Diseases	Copenhagen
Germany	Universitatsklinikum Bonn, Medizinische Klinik I - Bereich Infektiologie/HIV der Medizinischen Klinik	Bonn	Nordrhein-Westfalen
Germany	Universitatsklinikum Koeln Klinik I fur Innere Medizin Klinisches Studienzentrum fur Infektiologie I	Cologne
Germany	Universitätsklinikum Frankfurt -Medizinische Klinik II - Infektiologie	Frankfurt
Greece	Medical School of Athens University - Evangelismos Hospital - Department of Critical Care and Pulmonary Services	Athens
Greece	AHEPA University Hospital - 1st Department of Internal Medicine	Thessaloniki	Central Macedonia
Japan	National Center for Global Health and Medicine Hospital - Disease Control and Prevention Center	Tokyo
Korea, Republic of	Seoul National University Bundang Hospital - Division of Infectious Diseases	Bundang-gu Seongnam-si	Gyeonggi-do
Korea, Republic of	Seoul National University Hospital	Seoul	Jongno-gu
Mexico	Instituto Nacional de Ciencias Medicas y Nutrición Salvador Zubirán - Departamento de Infectologia	Mexico City
Mexico	Instituto Nacional de Enfermedades Respiratorias (INER) - Ismael Cosío Villegas	Mexico City
Singapore	National Centre for Infectious Diseases	Singapore
Spain	Hospital Clinic Barcelona, Servicio de Salud Internacional	Barcelona	Cataluña
Spain	Hospital Germans Trias i Pujol - Servei Malalties Infeccioses	Barcelona	Cataluña
United Kingdom	Royal Sussex County Hospital - Department of Intensive Care Medicine	East Sussex	Brighton
United Kingdom	John Radcliffe Hospital	Headington, Oxford
United Kingdom	St. James's University Hospital - Infectious Diseases	Leeds	West Yorkshire
United Kingdom	Royal Victoria Infirmary - Department of Infectious Diseases	Level 6, Ward 19	Newcastle Upon Tyne
United Kingdom	Saint Thomas' Hospital - Directorate of Infection	London	London, City Of
United States	Johns Hopkins Hospital - Medicine - Infectious Diseases	Baltimore	Maryland
United States	University of Maryland School of Medicine - Center for Vaccine Development - Baltimore	Baltimore	Maryland
United States	National Institutes of Health - Clinical Center, National Institute of Allergy and Infectious Diseases Laboratory Of Immunoregulation, Clinical Research Section	Bethesda	Maryland
United States	Walter Reed National Military Medical Center	Bethesda	Maryland
United States	University of Alabama at Birmingham School of Medicine - Infectious Disease	Birmingham	Alabama
United States	Massachusetts General Hospital - Infectious Diseases	Boston	Massachusetts
United States	Montefiore Medical Center - Infectious Diseases	Bronx	New York
United States	University of Virginia - Acute Care Surgery	Charlottesville	Virginia
United States	Northwestern Hospital - Infectious Disease	Chicago	Illinois
United States	University of Illinois at Chicago College of Medicine - Division of Infectious Diseases	Chicago	Illinois
United States	Emory Vaccine Center - The Hope Clinic	Decatur	Georgia
United States	Denver Health Division of Hospital Medicine - Main Campus	Denver	Colorado
United States	Duke Human Vaccine Institute - Duke Vaccine and Trials Unit	Durham	North Carolina
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	University of Texas Medical Branch - Division of Infectious Disease	Galveston	Texas
United States	Penn State Health Milton S. Hershey Medical Center - Division of Infectious Diseases	Hershey	Pennsylvania
United States	Baylor College of Medicine - Molecular Virology and Microbiology	Houston	Texas
United States	EvergreenHealth Infectious Disease Service	Kirkland	Washington
United States	University of California San Diego Health - Jacobs Medical Center	La Jolla	California
United States	University of California Los Angeles Medical Center - Westwood Clinic	Los Angeles	California
United States	University of Minnesota Medical Center, Fairview - Infectious Diseases and International Medicine	Minneapolis	Minnesota
United States	Vanderbilt University Medical Center - Infectious Diseases	Nashville	Tennessee
United States	Southeast Louisiana Veterans Health Care System - Section of Infectious Diseases	New Orleans	Louisiana
United States	New York University School of Medicine - Langone Medical Center - Microbiology - Parasitology	New York	New York
United States	University of Nebraska Medical Center - Infectious Diseases	Omaha	Nebraska
United States	University of California Irvine Medical Center - Infectious Disease	Orange	California
United States	VA Palo Alto Health Care System - Infectious Diseases	Palo Alto	California
United States	Hospital of the University of Pennsylvania - Infectious Diseases	Philadelphia	Pennsylvania
United States	Naval Medical Center Portsmouth - Infectious Disease Division	Portsmouth	Virginia
United States	University of Rochester Medical Center - Vaccine Research Unit	Rochester	New York
United States	University of California Davis Medical Center - Internal Medicine - Infectious Disease	Sacramento	California
United States	Saint Louis University - Center for Vaccine Development	Saint Louis	Missouri
United States	University of Texas Health Science Center at San Antonio - Infectious Diseases	San Antonio	Texas
United States	Naval Medical Center San Diego - Infectious Disease Clinic	San Diego	California
United States	University of California San Francisco - Zuckerberg San Francisco General Hospital - Division of Human Immunodeficiency Virus, Infectious Disease, and Global Medicine	San Francisco	California
United States	The University of Washington - Virology Research Clinic	Seattle	Washington
United States	Providence Sacred Heart Medical Center	Spokane	Washington
United States	Stanford University - Stanford Hospital and Clinics - Pediatrics - Infectious Diseases	Stanford	California
United States	Madigan Army Medical Center - Infectious Disease Clinic	Tacoma	Washington
United States	Cedars Sinai Medical Center	West Hollywood	California
United States	University of Massachusetts Medical School - Infectious Diseases and Immunology	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

United States,  Denmark,  Germany,  Greece,  Japan,  Korea, Republic of,  Mexico,  Singapore,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Recovery	Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Not hospitalized, no limitations on activities.	Day 1 through Day 29
Primary	Time to Recovery by Race	Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Not hospitalized, no limitations on activities.	Day 1 through Day 29
Primary	Time to Recovery by Ethnicity	Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Not hospitalized, no limitations on activities.	Day 1 through Day 29
Primary	Time to Recovery by Sex	Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Not hospitalized, no limitations on activities.	Day 1 through Day 29
Secondary	Change From Baseline in Alanine Transaminase (ALT)	Blood to evaluate ALT was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.	Days 1, 3, 5, 8, 11, 15 and 29
Secondary	Change From Baseline in Aspartate Transaminase (AST)	Blood to evaluate AST was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.	Days 1, 3, 5, 8, 11, 15 and 29
Secondary	Change From Baseline in Creatinine	Blood to evaluate serum creatinine was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.	Days 1, 3, 5, 8, 11, 15 and 29
Secondary	Change From Baseline in Glucose	Blood to evaluate serum glucose was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.	Days 1, 3, 5, 8, 11, 15 and 29
Secondary	Change From Baseline in Hemoglobin	Blood to evaluate hemoglobin was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.	Days 1, 3, 5, 8, 11, 15 and 29
Secondary	Change From Baseline in Platelets	Blood to evaluate platelets was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.	Days 1, 3, 5, 8, 11, 15 and 29
Secondary	Change From Baseline in Prothrombin Time (PT)	Blood to evaluate PT was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.	Days 1, 3, 5, 8, 11, 15 and 29
Secondary	Change From Baseline in Total Bilirubin	Blood to evaluate total bilirubin was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.	Days 1, 3, 5, 8, 11, 15 and 29
Secondary	Change From Baseline in White Blood Cell Count (WBC)	Blood to evaluate WBC was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.	Days 1, 3, 5, 8, 11, 15 and 29
Secondary	Change From Baseline in Neutrophils	Blood to evaluate neutrophils was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.	Days 1, 3, 5, 8, 11, 15 and 29
Secondary	Change From Baseline in Lymphocytes	Blood to evaluate lymphocytes was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.	Days 1, 3, 5, 8, 11, 15 and 29
Secondary	Change From Baseline in Monocytes	Blood to evaluate monocytes was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.	Days 1, 3, 5, 8, 11, 15 and 29
Secondary	Change From Baseline in Basophils	Blood to evaluate basophils was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.	Days 1, 3, 5, 8, 11, 15 and 29
Secondary	Change From Baseline in Eosinophils	Blood to evaluate eosinophils was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.	Days 1, 3, 5, 8, 11, 15 and 29
Secondary	Change in National Early Warning Score (NEWS) From Baseline	The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure. The minimum score is 0, representing the better outcome, and the maximum value is 19, representing the worse outcome.	Days 1, 3, 5, 8, 11, 15, 22, and 29
Secondary	Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 1	The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.	Day 1
Secondary	Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 3	The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.	Day 3
Secondary	Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 5	The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.	Day 5
Secondary	Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 8	The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.	Day 8
Secondary	Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 11	The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.	Day 11
Secondary	Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 15	The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.	Day 15
Secondary	Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 22	The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.	Day 22
Secondary	Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 29	The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.	Day 29
Secondary	Percentage of Participants Reporting Grade 3 and 4 Clinical and/or Laboratory Adverse Events (AEs)	Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening.	Day 1 through Day 29
Secondary	Percentage of Participants Reporting Serious Adverse Events (SAEs)	An SAE is defined as an AE or suspected adverse reaction is considered serious if, in the view of either the investigator or the sponsor, it results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.	Day 1 through Day 29
Secondary	Percentage of Participants Discontinued or Temporarily Suspended From Investigational Therapeutics	Participants may have been discontinued from investigational therapeutics due to discharge or death. The halting or slowing of the infusion for any reason was collected, as was missed doses in the series of 10 doses.	Day 1 through Day 10
Secondary	Duration of Hospitalization	Duration of hospitalization was determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die.	Day 1 through Day 29
Secondary	Duration of New Non-invasive Ventilation or High Flow Oxygen Use	Duration of new non-invasive ventilation or high flow oxygen use was measured in days among participants who were not on non-invasive ventilation or high-flow oxygen use at baseline, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die	Day 1 through Day 29
Secondary	Duration of New Oxygen Use	Duration of new oxygen use was measured in days among participants who were not on oxygen at baseline, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die; .	Day 1 through Day 29
Secondary	Duration of New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use	Duration of new ventilator or ECMO use was measured in days among participants who were not on a ventilator or ECMO at baseline, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die	Day 1 through Day 29
Secondary	Percentage of Participants Requiring New Non-invasive Ventilation or High-flow Oxygen Use	New non-invasive ventilation or high-flow oxygen use was determined as the percentage of subject not on non-invasive ventilation or high-flow oxygen at baseline.	Day 1 through Day 29
Secondary	Percentage of Participants Requiring New Oxygen Use	The percentage of participants requiring new oxygen use was determined as the percentage of participants not requiring oxygen at baseline	Day 1 through Day 29
Secondary	Percentage of Participants Requiring New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use	The percentage of participants requiring new ventilator or ECMO use was determined as the percentage not on a ventilator or ECMO at baseline	Day 1 through Day 29
Secondary	Mean Change in the Ordinal Scale	The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. A positive change indicates a worsening and a negative change is an improvement.	Day 1, 3, 5, 8, 11, 15, 22, and 29
Secondary	14-day Participant Mortality	The mortality rate was determined as the proportion of participants who died by study Day 15.	Day 1 through Day 15
Secondary	29-day Participant Mortality	The mortality rate was determined as the proportion of participants who died by study Day 29.	Day 1 through Day 29
Secondary	Time to an Improvement by at Least One Category Using an Ordinal Scale	The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. Time to improvement by at least one category was determined for each participant	Day 1 through Day 29
Secondary	Time to an Improvement of at Least Two Categories Using an Ordinal Scale	The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. Time to improvement by at least two categories was determined for each participant	Day 1 through Day 29
Secondary	Time to Discharge or to a NEWS of 2 or Less and Maintained for 24 Hours, Whichever Occurs First	The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure. The minimum score is 0, representing the better outcome, and the maximum value is 19, representing the worse outcome. The time to discharge or a NEWS of less than or equal to 2 was determined for each participant.	Day 1 through Day 29