A Randomized, Double-blind, Placebo-controlled, Multi-site, Phase III Study to Evaluate the Safety and Efficacy of CD24Fc in COVID-19 Treatment
Latest Information Update: 14 Dec 2023
At a glance
- Drugs Efprezimod alfa (Primary)
- Indications COVID-19 respiratory infection; Respiratory insufficiency
- Focus Adverse reactions; Registrational; Therapeutic Use
- Acronyms SAC-COVID
- Sponsors OncoImmune
- 01 May 2022 Primary endpoint (Time to Improvement in Coronavirus Disease 2019 (COVID-19) Clinical Status) has been met as per results published in The Lancet Infectious Diseases
- 01 May 2022 Results published in The Lancet Infectious Diseases
- 15 Apr 2021 According to a Merck and Co media release, given timeline and these technical, clinical and regulatory uncertainties, the availability of a number of medicines for patients hospitalized with COVID-19, and the need to concentrate Mercks resources on accelerating the development and manufacture of the most viable therapeutics and vaccines, Merck has determined to discontinue development of MK-7110 for COVID-19.
Most Recent Events
Trial Overview
Outcome
Purpose
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.
Comments
According to a Merck and Co media release, Merck subsequently received feedback from the US FDA that additional data, beyond the study conducted by OncoImmune, would be needed to support a potential Emergency Use Authorization application. Based on the additional research that would be required-new clinical trials as well as research related to manufacturing at scale, MK-7110 would not be expected to become available until the first half of 2022.Given this timeline and these technical, clinical and regulatory uncertainties, the availability of a number of medicines for patients hospitalized with COVID-19, and the need to concentrate Mercks resources on accelerating the development and manufacture of the most viable therapeutics and vaccines, Merck has determined to discontinue development of MK-7110 for COVID-19 (as of 15th Apr 2021).
Primary Endpoints
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 [1]
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
Other Endpoints
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
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
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
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
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
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
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
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
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
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
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
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
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 [2]
Diseases Treated
| Indication | Qualifiers | Patient Segments |
|---|---|---|
| COVID-19 respiratory infection | treatment | severe |
| Respiratory insufficiency | treatment | - |
Biomarker
| NCT Number | Biomarker Name | Biomarker Function |
|---|---|---|
| NCT04317040 | D-dimer | Outcome Measure |
Subjects
- Subject Type patients
-
Number
Planned: 270
Actual: 234
- Sex male & female
- Age Group ≥ 18 years; adult
Patient 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
Patient 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)
Trial Details
Identifiers
| Identifier | Owner |
|---|---|
| NCT04317040 | ClinicalTrials.gov: US National Institutes of Health |
| MK7110-007 | Merck and Co |
| CD24Fc007 | - |
| 20200674 | - |
| 7110-007 | - |
Organisations
- Sponsors OncoImmune
- Affiliations Merck & Co; OncoImmune
Trial Dates
-
Initiation Dates
Planned : 01 May 2020
Actual : 24 Apr 2020
-
Primary Completion Dates
Planned : 31 Oct 2020
Actual : 20 Oct 2020
-
End Dates
Planned : 30 Apr 2021
Actual : 20 Oct 2020
Other Details
- Design double-blind; multicentre; parallel; prospective; randomised
- Phase of Trial Phase III
- Location USA
- Focus Adverse reactions; Registrational; Therapeutic Use
Interventions
| Drugs | Route | Formulation |
|---|---|---|
| Efprezimod alfaPrimary Drug | Intravenous | Infusion |
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 Name: Human CD24, Human IgG Fc Fusion Protein, MK-7110
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
Results
Therapeutic efficacy
Phase III: Interim results from the phase III SAC-COVID trial conducted in 203 adult patients with severe COVID-2019 infections indicated that, patients who received efprezimod alfa showed 60% better chance to achieve clinical recovery than those who received placebo (P=0.005). The median time to recovery was 6 days for patients treated with efprezimod alfa compared with 10 days in the placebo group. In addition, the risk of death or respiratory failure is reduced by more than 50%. Patients treated with efprezimod alfa and remdesivir recovered 7 days earlier than those who received remdesivir and placebo (median time to recovery 6 days vs 13 days). Those who were treated with efprezimod alfa and corticosteroids recovered 10 days earlier than those who received corticosteroids and placebo (median time to recovery 5 days vs 15 days) [3] . In the phase III SAC-COVID trial conducted in adult patients with severe COVID-2019 infections, interim analysis post treatment with efprezimod alfa in 70 patients showed low mortality rate (5%) [4] .
Adverse events
Phase III: In interim analysis from the phase III SAC-COVID trial conducted in adult patients with severe COVID-2019 infections, efprezimod alfa showed favourable safety profile. The drug did not show any infusion site reaction or other drug-related adverse events. The data were reported from 70 patients [4] .
Publications
-
Welker J, Pulido JD, Catanzaro AT, Malvestutto CD, Li Z, Cohen JB, et al. Efficacy and safety of CD24Fc in hospitalised patients with COVID-19: a randomised, double-blind, placebo-controlled, phase 3 study. Lancet-Infect-Dis 2022;22(5):611-621.
PubMed | CrossRef Fulltext -
OncoImmunes. OncoImmunes SACCOVID(Tm) (CD24Fc) Exhibits Superb Therapeutic EfficacyA Potential Breakthrough in Treating Severe and Critical COVID-19. Media-Rel 2020;.
Media Release -
OncoImmune. OncoImmune, Inc. Reports Progress on its Phase III Clinical Trial testing CD24Fc for Severe and Critical COVID-19. Media-Rel 2020;.
Media Release
Trial Centres
Investigators
| Investigator | Centre Name | Trial Centre Country |
|---|---|---|
| James Welker, MD | Anne Arundel Medical Center |
-
|
|
Martin Devenport, PhD
(410) 2070582
show details
mdevenport@oncoimmune.com |
OncoImmune, Inc. |
-
|
|
Pan Zheng, MD, PhD
2027516823 pzheng@oncoimmune.com
show details
|
OncoImmune, Inc. |
-
|
Centres
| Centre Name | Location | Trial Centre Country |
|---|---|---|
| Anne Anundel Medical Center | Annapolis, Maryland | USA |
| Anne Arundel Medical Center |
-
|
-
|
| Atlantic Health System | Morristown, New Jersey | USA |
| Baptist Health Research Institute | Jacksonville, Florida | USA |
| Cooper University Hospital | Camden, New Jersey | USA |
| Henry Ford Health System | Detroit, Michigan | USA |
| Institute of Human Virology, University of Maryland Baltimore | Baltimore, Maryland | USA |
| OncoImmune, Inc. |
-
|
-
|
| Shady Grove Medical Center | Rockville, Maryland | USA |
| The Christ Hospital | Cincinnati, Ohio | USA |
| The Ohio State University Medical Center | Columbus, Ohio | USA |
| University Hospitals of Cleveland | Cleveland, Ohio | USA |
| University Medical Center of Southern Nevada | Las Vegas, Nevada | USA |
| University of Texas at Houston | Houston, Texas | USA |
| White Oak Medical Center | Silver Spring, Maryland | USA |
Trial History
| Event Date | Event Type | Comment |
|---|---|---|
| 14 Dec 2023 | Other trial event | Last checked against ClinicalTrials.gov record. Updated 14 Dec 2023 |
| 01 May 2022 | Endpoint met | Primary endpoint (Time to Improvement in Coronavirus Disease 2019 (COVID-19) Clinical Status) has been met as per results published in The Lancet Infectious Diseases Updated 19 May 2022 |
| 01 May 2022 | Results | Results published in The Lancet Infectious Diseases Updated 19 May 2022 |
| 22 Jul 2021 | Biomarker Update | Biomarkers information updated Updated 17 Sep 2021 |
| 15 Apr 2021 | Other trial event | According to a Merck and Co media release, given timeline and these technical, clinical and regulatory uncertainties, the availability of a number of medicines for patients hospitalized with COVID-19, and the need to concentrate Mercks resources on accelerating the development and manufacture of the most viable therapeutics and vaccines, Merck has determined to discontinue development of MK-7110 for COVID-19. Updated 19 Apr 2021 |
| 15 Apr 2021 | Other trial event | According to a Merck and Co media release, Merck subsequently received feedback from the US FDA that additional data, beyond the study conducted by OncoImmune, would be needed to support a potential Emergency Use Authorization application. Based on the additional research that would be required-new clinical trials as well as research related to manufacturing at scale, MK-7110 would not be expected to become available until the first half of 2022. Updated 19 Apr 2021 |
| 10 Feb 2021 | Status change - completed | Status changed from active, no longer recruiting to completed. Updated 12 Feb 2021 |
| 05 Feb 2021 | Completion date | Planned End Date changed from 30 Dec 2020 to 30 Apr 2021. Updated 09 Feb 2021 |
| 04 Feb 2021 | Other trial event | According to a Merck and Co media release, full study results are expected in the first quarter of 2021. Updated 09 Feb 2021 |
| 22 Nov 2020 | Completion date | Planned End Date changed from 1 Dec 2020 to 30 Dec 2020. Updated 26 Nov 2020 |
| 24 Sep 2020 | Interim results | Topline results of the planned interim analysis (n=203 enrolled, 146 patients achieved clinical recovery from COVID-19) presented in an OncoImmune media release. Updated 07 Dec 2020 |
| 24 Sep 2020 | Other trial event | According to an OncoImmune media release, this study is partially funded through a grant from the National Cancer Institute. Updated 29 Sep 2020 |
| 24 Sep 2020 | Other trial event | Planned primary completion date changed from 1 Sep 2020 to 31 Oct 2020. Updated 28 Sep 2020 |
| 24 Sep 2020 | Status change - active, no longer recruiting | Status changed from recruiting to active, no longer recruiting. Updated 28 Sep 2020 |
| 09 Sep 2020 | Other trial event | According to an OncoImmune media release, the trial is near its enrollment target with topline readouts expected soon. Updated 10 Sep 2020 |
| 01 Sep 2020 | Other trial event | Planned number of patients changed from 230 to 270. Updated 04 Sep 2020 |
| 14 Jun 2020 | Interim results | Preliminary Results published in the OncoImmune Media Release. Updated 17 Jun 2020 |
| 14 Jun 2020 | Other trial event | According to an OncoImmune media release, the company reached an important milestone in this study on June 9, 2020. The first 70 patients have been randomized and received either CD24Fc or placebo as the treatment for severe COVID-19. After reviewing the safety data, the Institutional Review Board has approved continuing enrollment while interim analysis occurs. Updated 17 Jun 2020 |
| 22 May 2020 | Completion date | Planned End Date changed from 1 May 2022 to 1 Dec 2020. Updated 28 May 2020 |
| 22 May 2020 | Other trial event | Planned primary completion date changed from 1 May 2021 to 1 Sep 2020. Updated 28 May 2020 |
| 21 Apr 2020 | Other trial event | According to an Oncoimmune media release, as the drug has a novel mechanism of action, it will likely synergize with other drugs, including antiviral treatments such as chloroquine and Remdesivir, or other immune modulators targeting cytokines or their receptors. Therefore, the trial will accept patients undergoing, or intending to enroll in trials testing other experimental therapies. Updated 22 Apr 2020 |
| 21 Apr 2020 | Other trial event | According to an OncoImmune media release, this study will involve 10 centers across the country. Dr. Joel Chua Assistant Professor of Medicine, Division of Clinical Care and Research, Institute of Human Virology at the University of Maryland School of Medicine is the clinical principle investigator for the University of Maryland Medical Center. ClinSmart, LLC of Newton, Pennsylvania is the Clinical Research Organization contracted to manage the trial. Updated 22 Apr 2020 |
| 08 Apr 2020 | Other trial event | According to an OncoImmune media release, the company has received a study-may-proceed letter from the FDA. Updated 14 Apr 2020 |
| 08 Apr 2020 | Status change - recruiting | Status changed from not yet recruiting to recruiting. Updated 13 Apr 2020 |
| 23 Mar 2020 | New trial record | New trial record Updated 23 Mar 2020 |
Table of Contents
References
-
Welker J, Pulido JD, Catanzaro AT, Malvestutto CD, Li Z, Cohen JB, et al. Efficacy and safety of CD24Fc in hospitalised patients with COVID-19: a randomised, double-blind, placebo-controlled, phase 3 study. Lancet-Infect-Dis 2022;22(5):611-621.
PubMed | CrossRef Fulltext -
ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2023;.
Available from: URL: http://clinicaltrials.gov -
OncoImmunes. OncoImmunes SACCOVID(Tm) (CD24Fc) Exhibits Superb Therapeutic EfficacyA Potential Breakthrough in Treating Severe and Critical COVID-19. Media-Rel 2020;.
Media Release -
OncoImmune. OncoImmune, Inc. Reports Progress on its Phase III Clinical Trial testing CD24Fc for Severe and Critical COVID-19. Media-Rel 2020;.
Media Release -
Merck Announces Fourth-Quarter and Full-Year 2020 Financial Results. Media-Rel 2021;.
Media Release -
OncoImmune. OncoImmune Receives FDA Approval for COVID-19 Clinical Trial. Media-Rel 2020;.
Media Release -
Merck .
Media Release -
OncoImmune. OncoImmune, Inc. Raises $56 Million Series B Financing for Novel Cancer and COVID-19 Therapeutics. Media-Rel 2020;.
Media Release -
OncoImmune. OncoImmune Starts Phase III Clinical Trial Testing the Power of Dampening Inflammation to Virus-induced Cellular Injury in Severe COVID-19 Patients. Media-Rel 2020;.
Media Release
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