SAC-COVID: CD24Fc (MK-7110) as a Non-antiviral Immunomodulator in COVID-19 Treatment (MK-7110-007)

• Sponsor: OncoImmune, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04317040
• Collaborator: (none)
• Enrollment: 234
• Locations: 10
• Arms: 2
• Actual Duration (Months): 5.9
• Patients Per Site: 23.4
• Patients Per Site Per Month: 4

Study Details

Study Description

Brief Summary

This study evaluates the efficacy and safety of CD24Fc (MK-7110) in hospitalized adult participants who are diagnosed with coronavirus disease 2019 (COVID-19) and receiving oxygen support.

The primary hypothesis of the study is clinical improvement in the experimental group versus the control group.

Condition or Disease	Intervention/Treatment	Phase
Coronavirus Disease 2019 (COVID-19)	Drug: CD24Fc; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 234 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled, Multi-site, Phase III Study to Evaluate the Safety and Efficacy of CD24Fc in COVID-19 Treatment
• Actual Study Start Date: Apr 24, 2020
• Actual Primary Completion Date: Oct 20, 2020
• Actual Study Completion Date: Oct 20, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CD24Fc Participants receive single dose of 480 mg CD24Fc, diluted to 100 ml with normal saline, intravenous (IV) infusion in 60 minutes on Day 1.	Drug: CD24Fc; CD24Fc is given on Day 1.; Other Names: Human CD24 Human IgG Fc Fusion Protein MK-7110
Placebo Comparator: Placebo Participants receive single dose of placebo as normal saline solution 100 ml, IV infusion in 60 minutes, on Day 1.	Drug: Placebo; Placebo is given on Day 1.; Other Names: Saline

Outcome Measures

Primary Outcome Measures

1. Time to Improvement in Coronavirus Disease 2019 (COVID-19) Clinical Status [Up to Day 29]

   Time to improvement in COVID-19 clinical status: defined as time (days) required from start of treatment to improvement of clinical status severe - moderate/mild or improvement from score 2-4 to ≥5 sustained without drop below 5 within 28 days from randomization, total follow-up period 29 days (Randomization Day 1 + 28 days follow up) per National Institute of Allergy & Infectious Diseases (NIAID) ordinal scale graded: 1=Death; 2=Hospitalized, on invasive mechanical ventilation (IMV)/extracorporeal membrane oxygenation (ECMO); 3=Hospitalized, on non-invasive ventilation (NIV)/high flow oxygen devices; 4=Hospitalized, require supplemental oxygen; 5=Hospitalized, no supplemental oxygen, require medical care; 6=Hospitalized, no supplemental oxygen, don't require medical care; 7=Not hospitalized, limitation on activities &/or require home oxygen; 8=Not hospitalized, no limitations on activities. Median time & 95% confidence intervals (CIs) were reported using Brookmeyer-Crowley method.

2. Number of Participants Who Experience an Adverse Event (AE) [Up to 30 days]

   An AE was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. Per protocol, only AEs with Common Terminology Criteria for AE (CTACAE) grade ≥3 were included. The number of participants who experienced an AE were reported.

Secondary Outcome Measures

1. Percentage of Participants Who Died or Had Respiratory Failure (RF) [Up to Day 29]

   RF was defined as the need for any of the following: 1) mechanical ventilation (MV), 2) ECMO, 3) NIV, or 4) high flow oxygen devices. Percentage of participants who died or had respiratory failure by Day 29 were reported.

2. Time to Disease Progression in Clinical Status of COVID-19 [Up to Day 29]

   Time to disease progression in clinical status is defined as the time (days) for progression from NIAID score (3 or 4) to (2 or 1) or from 2 to 1 within 28 days from randomization, total follow-up period 29 days (Randomization Day 1 + 28 days follow up). NIAID ordinal scale graded as: 1=Death; 2=Hospitalized, on IMV/ECMO; 3=Hospitalized, on NIV/high flow oxygen devices; 4= Hospitalized, require supplemental oxygen; 5=Hospitalized, no supplemental oxygen, require medical care; 6=Hospitalized, no supplemental oxygen, do not require medical care; 7=Not Hospitalized, limitation on activities and/or require home oxygen; 8=Not hospitalized, no limitations on activities.

3. Number of Participants Who Died Due to Any Cause [Up to Day 29]

   Number of participants who died due to any cause were assessed per protocol on Day 15 and Day 29.

4. Rate of Clinical Relapse [Up to Day 29]

   Rate of clinical relapse was defined as the percentage of participants who had initially reached score 5 on NIAID ordinal scale for more than one day but subsequently became dependent on oxygen support for more than 1 day within 28 days from randomization after initial recovery with a total follow-up period of 29 days (Day 1 of randomization plus 28 days of follow-up). NIAID ordinal scale graded as: 1=Death; 2=Hospitalized, on IMV/ECMO; 3=Hospitalized, on NIV/high flow oxygen devices; 4= Hospitalized, require supplemental oxygen; 5=Hospitalized, no supplemental oxygen, require medical care; 6=Hospitalized, no supplemental oxygen, do not require medical care; 7=Not hospitalized, limitation on activities and/or require home oxygen; 8=Not hospitalized, no limitations on activities. Clopper-Pearson method was used to report the 95% CI.

5. Conversion Rate of COVID-19 Clinical Status [Up to Day 15]

   Conversion rate of COVID-19 clinical status on days 8 and 15 was defined as the percentage of participants who changed from NIAID ordinal score 2, 3, 4 to score 5 or higher and reported. NIAID ordinal scale graded as: 1=Death; 2=Hospitalized, on IMV/ECMO; 3=Hospitalized, on NIV/high flow oxygen devices; 4= Hospitalized, require supplemental oxygen; 5=Hospitalized, no supplemental oxygen, require medical care; 6=Hospitalized, no supplemental oxygen, do not require medical care; 7=Not hospitalized, limitation on activities and/or require home oxygen; 8=Not hospitalized, no limitations on activities.

6. Time to Hospital Discharge [Up to Day 29]

   The hospital discharge time was defined as the time from randomization to discharge from the hospital and reported. Time to Hospital Discharge (days) from randomization is calculated as: Time to hospital discharge = Date of hospital discharge - Date of randomization.

7. Duration of MV [Up to Day 29]

   MV included IMV and NIV. Duration of MV (days) was calculated as: End Date of MV - Start Date of MV + 1 and reported.

8. Duration of Pressors [Up to Day 29]

   Pressor administration included norepinephrine, epinephrine, vasopressin, dopamine and phenylephrine. Duration of pressor (days) was defined as: End Date of Pressor - Start Date of Pressor + 1 and reported.

9. Duration of ECMO [Up to Day 29]

   Duration of ECMO treatment (days) was calculated as: End Date of ECMO Treatment - Start Date of ECMO Treatment + 1 and reported.

10. Duration of High Flow Oxygen Therapy [Up to Day 29]

    Duration of oxygen therapy (oxygen inhalation by high flow nasal cannula or mask) (days) was calculated as: End Date of high flow oxygen therapy - Start Date of high flow oxygen therapy + 1 and reported.

11. Length of Hospital Stay [Up to 90 days]

    Length of Hospital Stay (Days) was defined as date of discharge - date of admission + 1 and reported. Data presented below include hospitalization time prior to enrollment in the study with total duration of up to 90 days.

12. Change From Baseline in Absolute Lymphocyte Count [Baseline and up to Day 15]

    Blood samples were collected to present the change from baseline in the absolute lymphocyte count on days 1, 4, 8, and 15 in peripheral blood. To calculate the change from baseline in absolute lymphocyte count at specific timepoints (Days 1, 4, 8 and 15), only the participants who had both, a baseline, and a post baseline value at the specific timepoint (Days 1, 4, 8 and 15) were included in the analysis.

13. Change From Baseline in D-Dimer Concentration [Baseline and up to Day 15]

    Blood samples were collected to present the change from baseline in the D-dimer concentration on days 4, 8 and 15 in peripheral blood. To calculate change from baseline in D-dimer concentration at specific timepoints (Days 4, 8 and 15), only the participants who had both, a baseline, and a post baseline value at the specific timepoint (Days 4, 8 and 15) were included in the analysis.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosed with coronavirus disease 2019 (COVID-19) and confirmed severe acute respiratory syndrome coronavirus 2 (SARS-coV-2) viral infection

• Severe or critical COVID-19, or National Institute of Allergy and Infectious Diseases (NIAID) 8-point ordinal score 2, 3 or 4 (Scale 2: requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Scale 3: non-invasive ventilation or high flow oxygen devices; Scale 4: supplemental oxygen support; a peripheral capillary oxygen saturation (SpO2) </= 94% or tachypnea (respiratory rate

/= 24 breaths/min). Intubation should be within 7 days

Exclusion Criteria:

• Participants who are pregnant, breastfeeding, or have a positive pregnancy test result before enrollment

• Participants previously enrolled in the CD24Fc study

• Intubation for invasive mechanical ventilation is over 7 days

• Documented acute renal or hepatic failure

• The investigator believes that participating in the trial is not in the best interests of the participant, or the investigator considers unsuitable for enrollment (such as unpredictable risks or subject compliance issues)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Baptist Health Research Institute	Jacksonville	Florida	United States	32207
2	Anne Anundel Medical Center	Annapolis	Maryland	United States	21401
3	Institute of Human Virology, University of Maryland Baltimore	Baltimore	Maryland	United States	21201
4	Shady Grove Medical Center	Rockville	Maryland	United States	20850
5	White Oak Medical Center	Silver Spring	Maryland	United States	20904
6	Cooper University Hospital	Camden	New Jersey	United States	08103
7	Atlantic Health System	Morristown	New Jersey	United States	07960
8	University Hospitals of Cleveland	Cleveland	Ohio	United States	44106
9	The Ohio State University Medical Center	Columbus	Ohio	United States	43210
10	University of Texas at Houston	Houston	Texas	United States	77030

Sponsors and Collaborators

• OncoImmune, Inc.

Investigators

• Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 16, 2020

More Information

Publications

• Chen GY, Brown NK, Zheng P, Liu Y. Siglec-G/10 in self-nonself discrimination of innate and adaptive immunity. Glycobiology. 2014 Sep;24(9):800-6. doi: 10.1093/glycob/cwu068. Epub 2014 Jul 4. Review.
• Chen GY, Chen X, King S, Cavassani KA, Cheng J, Zheng X, Cao H, Yu H, Qu J, Fang D, Wu W, Bai XF, Liu JQ, Woodiga SA, Chen C, Sun L, Hogaboam CM, Kunkel SL, Zheng P, Liu Y. Amelioration of sepsis by inhibiting sialidase-mediated disruption of the CD24-SiglecG interaction. Nat Biotechnol. 2011 May;29(5):428-35. doi: 10.1038/nbt.1846. Epub 2011 Apr 10. Erratum in: Nat Biotechnol. 2012 Feb;30(2):193.
• Chen GY, Tang J, Zheng P, Liu Y. CD24 and Siglec-10 selectively repress tissue damage-induced immune responses. Science. 2009 Mar 27;323(5922):1722-5. doi: 10.1126/science.1168988. Epub 2009 Mar 5.
• Liu Y, Chen GY, Zheng P. Sialoside-based pattern recognitions discriminating infections from tissue injuries. Curr Opin Immunol. 2011 Feb;23(1):41-5. doi: 10.1016/j.coi.2010.10.004. Epub 2011 Jan 3. Review.
• Tian RR, Zhang MX, Liu M, Fang X, Li D, Zhang L, Zheng P, Zheng YT, Liu Y. CD24Fc protects against viral pneumonia in simian immunodeficiency virus-infected Chinese rhesus monkeys. Cell Mol Immunol. 2020 Aug;17(8):887-888. doi: 10.1038/s41423-020-0452-5. Epub 2020 May 7.
• Tian RR, Zhang MX, Zhang LT, Zhang P, Ma JP, Liu M, Devenport M, Zheng P, Zhang XL, Lian XD, Ye M, Zheng HY, Pang W, Zhang GH, Zhang LG, Liu Y, Zheng YT. CD24 and Fc fusion protein protects SIVmac239-infected Chinese rhesus macaque against progression to AIDS. Antiviral Res. 2018 Sep;157:9-17. doi: 10.1016/j.antiviral.2018.07.004. Epub 2018 Jul 3.

• Responsible Party: OncoImmune, Inc.
• ClinicalTrials.gov Identifier: NCT04317040
• Other Study ID Numbers: 7110-007; 20200674; CD24Fc-007-US; MK-7110-007
• First Posted: Mar 20, 2020
• Last Update Posted: Oct 15, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: COVID-19

Study Results

Participant Flow

Pre-assignment Detail	Of the 234 participants enrolled or randomized in the study, 229 participants received study medication and were evaluable for safety analyses.

Arm/Group Title	CD24Fc	Placebo
Arm/Group Description	Participants received single dose of CD24Fc 480 mg, diluted to 100 ml with normal saline, intravenous (IV) infusion in 60 minutes on Day 1.	Participants received single dose of placebo as normal saline solution 100 ml, IV infusion in 60 minutes on Day 1.
Period Title: Overall Study
STARTED	116	118
Treated	114	115
COMPLETED	98	98
NOT COMPLETED	18	20

Baseline Characteristics

Arm/Group Title	CD24Fc	Placebo	Total
Arm/Group Description	Participants received single dose of CD24Fc 480 mg, diluted to 100 ml with normal saline, intravenous (IV) infusion in 60 minutes on Day 1.	Participants received single dose of placebo as normal saline solution 100 ml, IV infusion in 60 minutes on Day 1.	Total of all reporting groups
Overall Participants	116	118	234
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	57.8 (14)	57.8 (14.2)	57.8 (14.1)
Sex: Female, Male (Count of Participants)
Female	45 38.8%	44 37.3%	89 38%
Male	71 61.2%	74 62.7%	145 62%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	41 35.3%	44 37.3%	85 36.3%
Not Hispanic or Latino	75 64.7%	74 62.7%	149 63.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 1.7%	2 1.7%	4 1.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	28 24.1%	22 18.6%	50 21.4%
White	53 45.7%	58 49.2%	111 47.4%
More than one race	0 0%	2 1.7%	2 0.9%
Unknown or Not Reported	33 28.4%	34 28.8%	67 28.6%

Outcome Measures

1. Primary Outcome

Title	Time to Improvement in Coronavirus Disease 2019 (COVID-19) Clinical Status
Description	Time to improvement in COVID-19 clinical status: defined as time (days) required from start of treatment to improvement of clinical status severe - moderate/mild or improvement from score 2-4 to ≥5 sustained without drop below 5 within 28 days from randomization, total follow-up period 29 days (Randomization Day 1 + 28 days follow up) per National Institute of Allergy & Infectious Diseases (NIAID) ordinal scale graded: 1=Death; 2=Hospitalized, on invasive mechanical ventilation (IMV)/extracorporeal membrane oxygenation (ECMO); 3=Hospitalized, on non-invasive ventilation (NIV)/high flow oxygen devices; 4=Hospitalized, require supplemental oxygen; 5=Hospitalized, no supplemental oxygen, require medical care; 6=Hospitalized, no supplemental oxygen, don't require medical care; 7=Not hospitalized, limitation on activities &/or require home oxygen; 8=Not hospitalized, no limitations on activities. Median time & 95% confidence intervals (CIs) were reported using Brookmeyer-Crowley method.
Time Frame	Up to Day 29

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	CD24Fc	Placebo
Arm/Group Description	Participants received single dose of CD24Fc 480 mg, diluted to 100 ml with normal saline, intravenous (IV) infusion in 60 minutes on Day 1.	Participants received single dose of placebo as normal saline solution 100 ml, IV infusion in 60 minutes on Day 1.
Measure Participants	116	118
Median (95% Confidence Interval) [Days]	6.0	10.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CD24Fc, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Hazard ratio (HR) and the associated 95% CIs were calculated based on Cox Regression model and p-value was calculated based on log-rank test, in accordance with the statistical analysis plan.
Statistical Test of Hypothesis	p-Value	0.0367
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.398
	Confidence Interval	(2-Sided) 95%; 1.020 to 1.918
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cox-Regression Model

2. Primary Outcome

Title	Number of Participants Who Experience an Adverse Event (AE)
Description	An AE was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. Per protocol, only AEs with Common Terminology Criteria for AE (CTACAE) grade ≥3 were included. The number of participants who experienced an AE were reported.
Time Frame	Up to 30 days

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of treatment.

Arm/Group Title	CD24Fc	Placebo
Arm/Group Description	Participants received single dose of CD24Fc 480 mg, diluted to 100 ml with normal saline, intravenous (IV) infusion in 60 minutes on Day 1.	Participants received single dose of placebo as normal saline solution 100 ml, IV infusion in 60 minutes on Day 1.
Measure Participants	114	115
Count of Participants [Participants]	32 27.6%	35 29.7%

3. Secondary Outcome

Title	Percentage of Participants Who Died or Had Respiratory Failure (RF)
Description	RF was defined as the need for any of the following: 1) mechanical ventilation (MV), 2) ECMO, 3) NIV, or 4) high flow oxygen devices. Percentage of participants who died or had respiratory failure by Day 29 were reported.
Time Frame	Up to Day 29

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	CD24Fc	Placebo
Arm/Group Description	Participants received single dose of CD24Fc 480 mg, diluted to 100 ml with normal saline, intravenous (IV) infusion in 60 minutes on Day 1.	Participants received single dose of placebo as normal saline solution 100 ml, IV infusion in 60 minutes on Day 1.
Measure Participants	116	118
Number [Percentage of Participants]	22.4 19.3%	28.0 23.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CD24Fc, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Risk difference (RD) and the associated 95% CIs were calculated based on Mantel-Haenszel method and p-value was calculated based on Chi-squared test, in accordance with the statistical analysis plan.
Statistical Test of Hypothesis	p-Value	0.3281
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.0555
	Confidence Interval	(2-Sided) 95%; -0.1665 to 0.0555
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mantel-Haenszel method

4. Secondary Outcome

Title	Time to Disease Progression in Clinical Status of COVID-19
Description	Time to disease progression in clinical status is defined as the time (days) for progression from NIAID score (3 or 4) to (2 or 1) or from 2 to 1 within 28 days from randomization, total follow-up period 29 days (Randomization Day 1 + 28 days follow up). NIAID ordinal scale graded as: 1=Death; 2=Hospitalized, on IMV/ECMO; 3=Hospitalized, on NIV/high flow oxygen devices; 4= Hospitalized, require supplemental oxygen; 5=Hospitalized, no supplemental oxygen, require medical care; 6=Hospitalized, no supplemental oxygen, do not require medical care; 7=Not Hospitalized, limitation on activities and/or require home oxygen; 8=Not hospitalized, no limitations on activities.
Time Frame	Up to Day 29

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	CD24Fc	Placebo
Arm/Group Description	Participants received single dose of CD24Fc 480 mg, diluted to 100 ml with normal saline, intravenous (IV) infusion in 60 minutes on Day 1.	Participants received single dose of placebo as normal saline solution 100 ml, IV infusion in 60 minutes on Day 1.
Measure Participants	116	118
Median (95% Confidence Interval) [Days]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CD24Fc, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Hazard ratio (HR) and the associated 95% CIs were calculated based on Cox Regression model and p-value was calculated based on log-rank test, in accordance with the statistical analysis plan.
Statistical Test of Hypothesis	p-Value	0.0306
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.558
	Confidence Interval	(2-Sided) 95%; 0.327 to 0.954
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cox Regression Model

5. Secondary Outcome

Title	Number of Participants Who Died Due to Any Cause
Description	Number of participants who died due to any cause were assessed per protocol on Day 15 and Day 29.
Time Frame	Up to Day 29

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	CD24Fc	Placebo
Arm/Group Description	Participants received single dose of CD24Fc 480 mg, diluted to 100 ml with normal saline, intravenous (IV) infusion in 60 minutes on Day 1.	Participants received single dose of placebo as normal saline solution 100 ml, IV infusion in 60 minutes on Day 1.
Measure Participants	116	118
Day 15	11 9.5%	8 6.8%
Day 29	16 13.8%	18 15.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CD24Fc, Placebo
	Comments	Day 15
	Type of Statistical Test	Other
	Comments	Risk difference (RD) and the associated 95% CIs were calculated based on Mantel-Haenszel method and p-value was calculated based on Chi-squared test, in accordance with the statistical analysis plan.
Statistical Test of Hypothesis	p-Value	0.4491
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.0270
	Confidence Interval	(2-Sided) 95%; -0.0430 to 0.0970
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mantel-Haenszel method used to report all-cause mortality by Day 15

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CD24Fc, Placebo
	Comments	Day 29
	Type of Statistical Test	Other
	Comments	Risk difference (RD) and the associated 95% CIs were calculated based on Mantel-Haenszel method and p-value was calculated based on Chi-squared test, in accordance with the statistical analysis plan.
Statistical Test of Hypothesis	p-Value	0.7512
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.0146
	Confidence Interval	(2-Sided) 95%; -0.1049 to 0.0756
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mantel-Haenszel method used to report all-cause mortality by Day 29

6. Secondary Outcome

Title	Rate of Clinical Relapse
Description	Rate of clinical relapse was defined as the percentage of participants who had initially reached score 5 on NIAID ordinal scale for more than one day but subsequently became dependent on oxygen support for more than 1 day within 28 days from randomization after initial recovery with a total follow-up period of 29 days (Day 1 of randomization plus 28 days of follow-up). NIAID ordinal scale graded as: 1=Death; 2=Hospitalized, on IMV/ECMO; 3=Hospitalized, on NIV/high flow oxygen devices; 4= Hospitalized, require supplemental oxygen; 5=Hospitalized, no supplemental oxygen, require medical care; 6=Hospitalized, no supplemental oxygen, do not require medical care; 7=Not hospitalized, limitation on activities and/or require home oxygen; 8=Not hospitalized, no limitations on activities. Clopper-Pearson method was used to report the 95% CI.
Time Frame	Up to Day 29

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	CD24Fc	Placebo
Arm/Group Description	Participants received single dose of CD24Fc 480 mg, diluted to 100 ml with normal saline, intravenous (IV) infusion in 60 minutes on Day 1.	Participants received single dose of placebo as normal saline solution 100 ml, IV infusion in 60 minutes on Day 1.
Measure Participants	116	118
Number (95% Confidence Interval) [Percentage of Participants]	4.3 3.7%	6.8 5.8%

7. Secondary Outcome

Title	Conversion Rate of COVID-19 Clinical Status
Description	Conversion rate of COVID-19 clinical status on days 8 and 15 was defined as the percentage of participants who changed from NIAID ordinal score 2, 3, 4 to score 5 or higher and reported. NIAID ordinal scale graded as: 1=Death; 2=Hospitalized, on IMV/ECMO; 3=Hospitalized, on NIV/high flow oxygen devices; 4= Hospitalized, require supplemental oxygen; 5=Hospitalized, no supplemental oxygen, require medical care; 6=Hospitalized, no supplemental oxygen, do not require medical care; 7=Not hospitalized, limitation on activities and/or require home oxygen; 8=Not hospitalized, no limitations on activities.
Time Frame	Up to Day 15

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	CD24Fc	Placebo
Arm/Group Description	Participants received single dose of CD24Fc 480 mg, diluted to 100 ml with normal saline, intravenous (IV) infusion in 60 minutes on Day 1.	Participants received single dose of placebo as normal saline solution 100 ml, IV infusion in 60 minutes on Day 1.
Measure Participants	116	118
Day 8	55.2 47.6%	42.4 35.9%
Day 15	71.6 61.7%	55.9 47.4%

8. Secondary Outcome

Title	Time to Hospital Discharge
Description	The hospital discharge time was defined as the time from randomization to discharge from the hospital and reported. Time to Hospital Discharge (days) from randomization is calculated as: Time to hospital discharge = Date of hospital discharge - Date of randomization.
Time Frame	Up to Day 29

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	CD24Fc	Placebo
Arm/Group Description	Participants received single dose of CD24Fc 480 mg, diluted to 100 ml with normal saline, intravenous (IV) infusion in 60 minutes on Day 1.	Participants received single dose of placebo as normal saline solution 100 ml, IV infusion in 60 minutes on Day 1.
Measure Participants	116	118
Median (95% Confidence Interval) [Days]	7.0	10.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CD24Fc, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Hazard ratio (HR) and the associated 95% CIs were calculated based on Cox Regression model and p-value was calculated based on log-rank test, in accordance with the statistical analysis plan.
Statistical Test of Hypothesis	p-Value	0.0311
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.416
	Confidence Interval	(2-Sided) 95%; 1.031 to 1.945
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cox Regression model

9. Secondary Outcome

Title	Duration of MV
Description	MV included IMV and NIV. Duration of MV (days) was calculated as: End Date of MV - Start Date of MV + 1 and reported.
Time Frame	Up to Day 29

Outcome Measure Data

Analysis Population Description

All randomized participants who received MV

Arm/Group Title	CD24Fc	Placebo
Arm/Group Description	Participants received single dose of CD24Fc 480 mg, diluted to 100 ml with normal saline, intravenous (IV) infusion in 60 minutes on Day 1.	Participants received single dose of placebo as normal saline solution 100 ml, IV infusion in 60 minutes on Day 1.
Measure Participants	28	39
Mean (Standard Deviation) [Days]	14.3 (12.34)	14.3 (8.85)

10. Secondary Outcome

Title	Duration of Pressors
Description	Pressor administration included norepinephrine, epinephrine, vasopressin, dopamine and phenylephrine. Duration of pressor (days) was defined as: End Date of Pressor - Start Date of Pressor + 1 and reported.
Time Frame	Up to Day 29

Outcome Measure Data

Analysis Population Description

All randomized participants who received pressors

Arm/Group Title	CD24Fc	Placebo
Arm/Group Description	Participants received single dose of CD24Fc 480 mg, diluted to 100 ml with normal saline, intravenous (IV) infusion in 60 minutes on Day 1.	Participants received single dose of placebo as normal saline solution 100 ml, IV infusion in 60 minutes on Day 1.
Measure Participants	20	24
Mean (Standard Deviation) [Days]	6.3 (5.59)	7.9 (8.86)

11. Secondary Outcome

Title	Duration of ECMO
Description	Duration of ECMO treatment (days) was calculated as: End Date of ECMO Treatment - Start Date of ECMO Treatment + 1 and reported.
Time Frame	Up to Day 29

Outcome Measure Data

Analysis Population Description

All randomized participants who received ECMO

Arm/Group Title	CD24Fc	Placebo
Arm/Group Description	Participants received single dose of CD24Fc 480 mg, diluted to 100 ml with normal saline, intravenous (IV) infusion in 60 minutes on Day 1.	Participants received single dose of placebo as normal saline solution 100 ml, IV infusion in 60 minutes on Day 1.
Measure Participants	0	1
Mean (Standard Deviation) [Days]	11.0 (NA)

12. Secondary Outcome

Title	Duration of High Flow Oxygen Therapy
Description	Duration of oxygen therapy (oxygen inhalation by high flow nasal cannula or mask) (days) was calculated as: End Date of high flow oxygen therapy - Start Date of high flow oxygen therapy + 1 and reported.
Time Frame	Up to Day 29

Outcome Measure Data

Analysis Population Description

All randomized participants who received high flow oxygen therapy

Arm/Group Title	CD24Fc	Placebo
Arm/Group Description	Participants received single dose of CD24Fc 480 mg, diluted to 100 ml with normal saline, intravenous (IV) infusion in 60 minutes on Day 1.	Participants received single dose of placebo as normal saline solution 100 ml, IV infusion in 60 minutes on Day 1.
Measure Participants	114	115
Mean (Standard Deviation) [Days]	13.8 (12.91)	13.0 (10.12)

13. Secondary Outcome

Title	Length of Hospital Stay
Description	Length of Hospital Stay (Days) was defined as date of discharge - date of admission + 1 and reported. Data presented below include hospitalization time prior to enrollment in the study with total duration of up to 90 days.
Time Frame	Up to 90 days

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	CD24Fc	Placebo
Arm/Group Description	Participants received single dose of CD24Fc 480 mg, diluted to 100 ml with normal saline, intravenous (IV) infusion in 60 minutes on Day 1.	Participants received single dose of placebo as normal saline solution 100 ml, IV infusion in 60 minutes on Day 1.
Measure Participants	116	118
Mean (Standard Deviation) [Days]	16.6 (16.27)	18.2 (13.54)

14. Secondary Outcome

Title	Change From Baseline in Absolute Lymphocyte Count
Description	Blood samples were collected to present the change from baseline in the absolute lymphocyte count on days 1, 4, 8, and 15 in peripheral blood. To calculate the change from baseline in absolute lymphocyte count at specific timepoints (Days 1, 4, 8 and 15), only the participants who had both, a baseline, and a post baseline value at the specific timepoint (Days 1, 4, 8 and 15) were included in the analysis.
Time Frame	Baseline and up to Day 15

Outcome Measure Data

Analysis Population Description

All randomized participants with lymphocyte data available

Arm/Group Title	CD24Fc	Placebo
Arm/Group Description	Participants received single dose of CD24Fc 480 mg, diluted to 100 ml with normal saline, intravenous (IV) infusion in 60 minutes on Day 1.	Participants received single dose of placebo as normal saline solution 100 ml, IV infusion in 60 minutes on Day 1.
Measure Participants	114	114
Baseline	2.357 (5.1173)	2.437 (4.7660)
Day 1	5.317 (8.0772)	5.125 (7.3979)
Day 4	2.373 (5.7549)	2.461 (4.2074)
Day 8	2.557 (4.7147)	1.839 (2.7319)
Day 15	1.965 (3.8555)	2.378 (4.6402)
Change from Baseline to Day 1	0.374 (2.0467)	-0.148 (0.7985)
Change from Baseline to Day 4	0.219 (5.2971)	0.053 (2.2800)
Change from Baseline to Day 8	0.575 (5.5692)	-0.491 (3.1128)
Change from Baseline to Day 15	0.558 (4.3613)	-0.280 (5.1603)

15. Secondary Outcome

Title	Change From Baseline in D-Dimer Concentration
Description	Blood samples were collected to present the change from baseline in the D-dimer concentration on days 4, 8 and 15 in peripheral blood. To calculate change from baseline in D-dimer concentration at specific timepoints (Days 4, 8 and 15), only the participants who had both, a baseline, and a post baseline value at the specific timepoint (Days 4, 8 and 15) were included in the analysis.
Time Frame	Baseline and up to Day 15

Outcome Measure Data

Analysis Population Description

All randomized participants with D-dimer concentration data available

Arm/Group Title	CD24Fc	Placebo
Arm/Group Description	Participants received single dose of CD24Fc 480 mg, diluted to 100 ml with normal saline, intravenous (IV) infusion in 60 minutes on Day 1.	Participants received single dose of placebo as normal saline solution 100 ml, IV infusion in 60 minutes on Day 1.
Measure Participants	104	108
Baseline	153.717 (1457.6865)	9.767 (12.4347)
Day 4	10.451 (16.1924)	13.885 (33.0328)
Day 8	13.224 (17.4246)	13.349 (17.2777)
Day 15	11.700 (7.9524)	13.892 (19.9369)
Change from Baseline to Day 4	-0.427 (9.6796)	3.971 (34.9427)
Change from Baseline to Day 8	-397.547 (2419.1594)	0.703 (18.3254)
Change from Baseline to Day 15	3.076 (10.0044)	-3.591 (19.0945)

Adverse Events

Time Frame	Serious adverse events (AEs), non-serious AEs and all-cause mortality were collected up to approximately 30 days.
Adverse Event Reporting Description	All-cause mortality was reported on all randomized participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment.
Arm/Group Title	CD24Fc		Placebo
Arm/Group Description	Participants received single dose of CD24Fc 480 mg, diluted to 100 ml with normal saline, intravenous (IV) infusion in 60 minutes on Day 1.		Participants received single dose of placebo as normal saline solution 100 ml, IV infusion in 60 minutes on Day 1.
All Cause Mortality
	CD24Fc		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/116 (13.8%)		18/118 (15.3%)
Serious Adverse Events
	CD24Fc		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/114 (22.8%)		27/115 (23.5%)
Blood and lymphatic system disorders
Anaemia	4/114 (3.5%)	4	1/115 (0.9%)	1
Cardiac disorders
Cardiac arrest	3/114 (2.6%)	3	2/115 (1.7%)	2
Cardio-respiratory arrest	2/114 (1.8%)	2	1/115 (0.9%)	1
Pulseless electrical activity	1/114 (0.9%)	1	0/115 (0%)	0
Gastrointestinal disorders
Gastrointestinal haemorrhage	1/114 (0.9%)	1	0/115 (0%)	0
General disorders
Chest pain	0/114 (0%)	0	1/115 (0.9%)	1
Multiple organ dysfunction syndrome	1/114 (0.9%)	1	0/115 (0%)	0
Ulcer haemorrhage	0/114 (0%)	0	1/115 (0.9%)	1
Infections and infestations
COVID-19 pneumonia	1/114 (0.9%)	1	1/115 (0.9%)	1
Escherichia bacteraemia	0/114 (0%)	0	1/115 (0.9%)	1
Septic shock	1/114 (0.9%)	1	0/115 (0%)	0
Investigations
Pulse absent	1/114 (0.9%)	1	0/115 (0%)	0
Metabolism and nutrition disorders
Acidosis	1/114 (0.9%)	1	0/115 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Chronic lymphocytic leukaemia	1/114 (0.9%)	1	0/115 (0%)	0
Nervous system disorders
Cerebrovascular accident	0/114 (0%)	0	1/115 (0.9%)	1
Hypoaesthesia	1/114 (0.9%)	1	0/115 (0%)	0
Subarachnoid haemorrhage	1/114 (0.9%)	1	0/115 (0%)	0
Renal and urinary disorders
Acute kidney injury	3/114 (2.6%)	3	2/115 (1.7%)	2
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/114 (0.9%)	1	1/115 (0.9%)	1
Acute respiratory failure	2/114 (1.8%)	2	0/115 (0%)	0
Dyspnoea	1/114 (0.9%)	1	0/115 (0%)	0
Hypoxia	1/114 (0.9%)	1	1/115 (0.9%)	1
Laryngeal oedema	1/114 (0.9%)	1	0/115 (0%)	0
Pneumothorax	1/114 (0.9%)	1	0/115 (0%)	0
Pulmonary embolism	0/114 (0%)	0	1/115 (0.9%)	1
Pulmonary fibrosis	1/114 (0.9%)	1	0/115 (0%)	0
Respiratory distress	0/114 (0%)	0	2/115 (1.7%)	2
Respiratory failure	5/114 (4.4%)	5	14/115 (12.2%)	14
Vascular disorders
Hypovolaemic shock	1/114 (0.9%)	1	0/115 (0%)	0
Orthostatic hypotension	0/114 (0%)	0	1/115 (0.9%)	1
Peripheral ischaemia	1/114 (0.9%)	1	0/115 (0%)	0
Shock haemorrhagic	0/114 (0%)	0	1/115 (0.9%)	1
Other (Not Including Serious) Adverse Events
	CD24Fc		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/114 (0%)		0/115 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Sponsor will support writing and publication of scientific reports, journal papers and oral presentations by the study principal investigator and others making scientific contribution to the research effort. Any reports, papers, and/or presentations must be reviewed and approved prior to submitting for publication.