Efprezimod Alfa (CD24Fc, MK-7110) as a Non-antiviral Immunomodulator in COVID-19 Treatment (MK-7110-007)
- Conditions
- Coronavirus Disease 2019 (COVID-19)
- Interventions
- Drug: Placebo
- Registration Number
- NCT04317040
- Lead Sponsor
- Oncoimmune, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 234
- 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
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Efprezimod alfa 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. Placebo Placebo Participants receive single dose of placebo as normal saline solution 100 ml, IV infusion in 60 minutes, on Day 1.
- Primary Outcome Measures
Name Time Method 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.
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
Name Time Method 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Trial Locations
- Locations (10)
Baptist Health Research Institute
🇺🇸Jacksonville, Florida, 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
Shady Grove Medical Center
🇺🇸Rockville, Maryland, United States
Anne Anundel Medical Center
🇺🇸Annapolis, Maryland, United States
White Oak Medical Center
🇺🇸Silver Spring, Maryland, United States
Atlantic Health System
🇺🇸Morristown, New Jersey, United States