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

Coronavirus Disease 2019 (COVID-19) Clinical Trial

— SAC-COVID  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04317040
• Other study ID #: 7110-007
• Secondary ID: 20200674CD24Fc-0
• Status: Completed
• Phase: Phase 3
• Start date: April 24, 2020
• Est. completion date: October 20, 2020

Study information

• Verified date: January 2023
• Source: OncoImmune, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 234
• Est. completion date: October 20, 2020
• Est. primary completion date: October 20, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Coronavirus Disease 2019 (COVID-19)
• COVID-19

Intervention

Drug:
• Efprezimod alfa
Efprezimod alfa is given on Day 1.
• Placebo
Placebo is given on Day 1.

Locations

Country	Name	City	State
United States	Anne Anundel Medical Center	Annapolis	Maryland
United States	Institute of Human Virology, University of Maryland Baltimore	Baltimore	Maryland
United States	Cooper University Hospital	Camden	New Jersey
United States	University Hospitals of Cleveland	Cleveland	Ohio
United States	The Ohio State University Medical Center	Columbus	Ohio
United States	University of Texas at Houston	Houston	Texas
United States	Baptist Health Research Institute	Jacksonville	Florida
United States	Atlantic Health System	Morristown	New Jersey
United States	Shady Grove Medical Center	Rockville	Maryland
United States	White Oak Medical Center	Silver Spring	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
OncoImmune, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Improvement in Coronavirus Disease 2019 (COVID-19) Clinical Status	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.	Up to Day 29
Primary	Number of Participants Who Experience an Adverse Event (AE)	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.	Up to 30 days
Secondary	Percentage of Participants Who Died or Had Respiratory Failure (RF)	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.	Up to Day 29
Secondary	Time to Disease Progression in Clinical Status of COVID-19	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.	Up to Day 29
Secondary	Number of Participants Who Died Due to Any Cause	Number of participants who died due to any cause were assessed per protocol on Day 15 and Day 29.	Up to Day 29
Secondary	Rate of Clinical Relapse	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.	Up to Day 29
Secondary	Conversion Rate of COVID-19 Clinical Status	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.	Up to Day 15
Secondary	Time to Hospital Discharge	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.	Up to Day 29
Secondary	Duration of MV	MV included IMV and NIV. Duration of MV (days) was calculated as: End Date of MV - Start Date of MV + 1 and reported.	Up to Day 29
Secondary	Duration of Pressors	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.	Up to Day 29
Secondary	Duration of ECMO	Duration of ECMO treatment (days) was calculated as: End Date of ECMO Treatment - Start Date of ECMO Treatment + 1 and reported.	Up to Day 29
Secondary	Duration of High Flow Oxygen Therapy	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.	Up to Day 29
Secondary	Length of Hospital Stay	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.	Up to 90 days
Secondary	Change From Baseline in Absolute Lymphocyte Count	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.	Baseline and up to Day 15
Secondary	Change From Baseline in D-Dimer Concentration	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.	Baseline and up to Day 15

External Links

•   Merck Oncology Clinical Trials Information