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

• ClinicalTrials.gov Identifier: NCT04317040
• Recruitment Status: Completed
• First Posted: March 20, 2020
• Results First Posted: October 15, 2021
• Last Update Posted: February 8, 2023
• Sponsor: OncoImmune, Inc.
• Information provided by (Responsible Party): OncoImmune, Inc.

Study Description

Brief Summary:

This study evaluates the efficacy and safety of efprezimod alfa 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: Efprezimod alfa; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• 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: April 24, 2020
• Actual Primary Completion Date: October 20, 2020
• Actual Study Completion Date: October 20, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Efprezimod alfa; Participants receive single dose of 480 mg efprezimod alfa, diluted to 100 ml with normal saline, intravenous (IV) infusion in 60 minutes on Day 1.	Drug: Efprezimod alfa; Efprezimod alfa 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 Name: Saline

Outcome Measures

Primary Outcome Measures :

1. Time to Improvement in Coronavirus Disease 2019 (COVID-19) Clinical Status [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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 efprezimod alfa 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

United States, Florida

Baptist Health Research Institute

Jacksonville, Florida, United States, 32207

United States, Maryland

Anne Anundel Medical Center

Annapolis, Maryland, United States, 21401

Institute of Human Virology, University of Maryland Baltimore

Baltimore, Maryland, United States, 21201

Shady Grove Medical Center

Rockville, Maryland, United States, 20850

White Oak Medical Center

Silver Spring, Maryland, United States, 20904

United States, New Jersey

Cooper University Hospital

Camden, New Jersey, United States, 08103

Atlantic Health System

Morristown, New Jersey, United States, 07960

United States, Ohio

University Hospitals of Cleveland

Cleveland, Ohio, United States, 44106

The Ohio State University Medical Center

Columbus, Ohio, United States, 43210

United States, Texas

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)

Documents provided by OncoImmune, Inc.:

Study Protocol and Statistical Analysis Plan  [PDF] August 16, 2020

More Information

Additional Information:

Merck Oncology Clinical Trials 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.

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.

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.

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.

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. No abstract available.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Welker J, Pulido JD, Catanzaro AT, Malvestutto CD, Li Z, Cohen JB, Whitman ED, Byrne D, Giddings OK, Lake JE, Chua JV, Li E, Chen J, Zhou X, He K, Gates D, Kaur A, Chen J, Chou HY, Devenport M, Touomou R, Kottilil S, Liu Y, Zheng P; SAC-COVID Study Team. Efficacy and safety of CD24Fc in hospitalised patients with COVID-19: a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Infect Dis. 2022 May;22(5):611-621. doi: 10.1016/S1473-3099(22)00058-5. Epub 2022 Mar 11.

Song NJ, Allen C, Vilgelm AE, Riesenberg BP, Weller KP, Reynolds K, Chakravarthy KB, Kumar A, Khatiwada A, Sun Z, Ma A, Chang Y, Yusuf M, Li A, Zeng C, Evans JP, Bucci D, Gunasena M, Xu M, Liyanage NPM, Bolyard C, Velegraki M, Liu SL, Ma Q, Devenport M, Liu Y, Zheng P, Malvestutto CD, Chung D, Li Z. Treatment with soluble CD24 attenuates COVID-19-associated systemic immunopathology. J Hematol Oncol. 2022 Jan 10;15(1):5. doi: 10.1186/s13045-021-01222-y.

• Responsible Party: OncoImmune, Inc.
• ClinicalTrials.gov Identifier: NCT04317040
• Other Study ID Numbers: 7110-007; 20200674 ( Other Identifier: WIRB ); CD24Fc-007-US ( Other Identifier: OncoImmune ); MK-7110-007 ( Other Identifier: Merck )
• First Posted: March 20, 2020
• Results First Posted: October 15, 2021
• Last Update Posted: February 8, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases