CD24Fc as a Non-antiviral Immunomodulator in COVID-19 Treatment (MK-7110-007) (SAC-COVID)
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|ClinicalTrials.gov Identifier: NCT04317040|
Recruitment Status : Completed
First Posted : March 20, 2020
Last Update Posted : July 22, 2021
The study is designed as a randomized, placebo-controlled, double blind, multicenter, Phase III trial to compare two COVID-19 treatment regimens in hospitalized adult participants who are diagnosed with COVID-19 and receiving oxygen support.
Arm A: CD24Fc (MK-7110)/Best Available Treatment; Arm B: placebo/ Best Available Treatment. CD24Fc will be administered as single dose of 480 mg via intravenous (IV) infusion on Day 1. Total of 270 subjects will be enrolled and randomized in 1:1 ratio to receive CD24Fc or placebo. All subjects will be treated with the best available treatment. The follow up period is 28 days.
The primary hypothesis of the study is clinical improvement in the experimental group vs the control group.
|Condition or disease||Intervention/treatment||Phase|
|COVID-19||Drug: CD24Fc Drug: Placebo||Phase 3|
As the newest global medical emergency, the COVID-19 (diagnosed SARS-CoV2 infection with lung involvement) exhibits features that are unlikely ameliorated by antivirals-based approaches alone. First, although the new coronavirus (SARS-CoV-2) infect lung and intestine, many patients suddenly take a turn for the worse even when the viral replication appears to be under control. Second, patients with serious or critical clinical symptoms show marked T cell lymphopenia that are more severe and more acute than human immunodeficiency virus (HIV) infection. Functional exhaustion of T cells is suggested by high expression of T-cell exhaustion markers, which again appears more acute than in HIV patients. Third, multiple cytokines are elevated among patients with severe clinical symptoms, which potentially explains the multiple organ failure associated with COVID-19. For these reasons, treatment of COVID-19 likely requires a combination of both antivirals and non-antivirals-based approaches.
CD24Fc is a biological immunomodulator in Phase II/III clinical trial stage. CD24Fc comprises the nonpolymorphic regions of CD24 attached to the Fc region of human immunoglobulin G1 (IgG1). We have shown that CD24 is an innate checkpoint against the inflammatory response to tissue injuries or danger-associated molecular patterns (DAMPs). Preclinical and clinical studies have demonstrated that CD24Fc effectively addresses the major challenges associated with COVID-19. First, a Phase I clinical trial on healthy volunteers not only demonstrated safety of CD24Fc, but also demonstrated its biological activity in suppressing expression of multiple inflammatory cytokines. Second, in a Phase II clinical trial in leukemia patients undergoing hematopoietic stem cell transplantation (HCT), three doses of CD24Fc effectively eliminated severe (Grade 3-4) acute graft vs host diseases (GVHD), which is caused by over reacting immune system and transplanted T cells attacking recipient target tissues. Third, in preclinical models of Human immunodeficiency virus (HIV)/ Simian immunodeficiency virus (SIV) infections, we have shown that CD24Fc ameliorated production of multiple inflammatory cytokines, reversed the loss of T lymphocytes as well as functional T cell exhaustion and reduced the leukocyte infiltration of multiple organs. It is particularly noteworthy that CD24Fc reduced the rate of pneumonia in SIV-infected Chinese rhesus monkey from 83% to 33%. Therefore, CD24Fc maybe a prime candidate for non-antiviral biological modifier for COVID-19 therapy. The phase III trial will involve 270 patients randomized into blinded placebo and CD24Fc arms, with time to clinical improvement from critical or severe to mild symptom as the primary endpoint.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||243 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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|
Experimental: CD24Fc Treatment
Single dose at Day 1, CD24Fc, 480mg, diluted to 100ml with normal saline, IV infusion in 60 minutes.
CD24Fc is given on Day 1.
Other Name: Human CD24 and human IgG Fc Fusion Protein
Placebo Comparator: Placebo
Single dose at Day 1, normal saline solution 100ml, IV infusion in 60 minutes.
Placebo is given on Day 1.
Other Name: Saline
- Time to Improvement in COVID-19 Clinical Status [ Time Frame: 29 days ]Time to improvement in COVID-19 clinical status is defined as the time (days) required from the start of treatment to the improvement of clinical status "severe" to "moderate/mild"; or improvement from "scale 2, 3, or 4" to "scale 5 or higher" based on the National Institute of Allergy and Infectious Diseases (NIAID) ordinal scales.
- Percentage of Participants Who Died or Had Respiratory Failure (RF) [ Time Frame: 29 days ]Percentage of participants who died or had respiratory failure, defined as the need for mechanical ventilation, extracorporeal membrane oxygenation (ECMO), non-invasive ventilation (NIV), or high flow oxygen devices, at Day 29
- Time to Disease Progression of COVID-19 [ Time Frame: 29 days ]Time for disease progression from NIAID scale 3 or 4 to need to be on invasive mechanical ventilation (IMV), or ECMO, or death, or from NIAID scale 2 to death.
- All-Cause of Death [ Time Frame: 15 days and 29 days ]All cause of death
- Rate of Clinical Relapse [ Time Frame: 29 days ]Rate of clinical relapse is defined by rate of return to oxygen support for more than 1 day within 29 days from randomization after initial recovery.
- Conversion Rate of Clinical Status at Day 8 [ Time Frame: 8 days ]Conversion rate of clinical status on day 8 (percentage of participants who changed from NIAID ordinal scale 2, 3, 4 to scale 5 or higher.
- Conversion Rate of Clinical Status at Day 15 [ Time Frame: 15 days ]Conversion rate of clinical status on day 15 (percentage of participants who changed from NIAID ordinal scale 2, 3, 4 to scale 5 or higher.
- Hospital Discharge Time [ Time Frame: 29 days ]The discharge time, calculated after the randomization.
- Duration of Mechanical Ventilation [ Time Frame: 29 days ]Duration of mechanical ventilation (IMV, NIV) (days)
- Duration of Pressors [ Time Frame: 29 days ]Duration of pressors (days)
- Duration of ECMO [ Time Frame: 29 days ]Duration of extracorporeal membrane oxygenation (days)
- Duration of High Flow Oxygen Therapy [ Time Frame: 29 days ]Duration of oxygen therapy (oxygen inhalation by high flow nasal cannula or mask) (days)
- Length of Hospital Stay [ Time Frame: 29 days ]Length of Hospital Stay (Days) is defined as date of discharge - date of admission +1. Hospital stay for participants will be reported.
- Absolute Lymphocyte Count [ Time Frame: 29 days ]Changes of absolute lymphocyte count in peripheral blood
- Change of D-Dimers [ Time Frame: 15 and 29 days ]The changes of plasma concentration of D-dimers
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04317040
|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|
|Study Director:||Medical Director||Merck Sharp & Dohme Corp.|