COVID-19
Conditions
Keywords
Adults, COVID-19, Multicenter, Putative, Therapeutics
Brief summary
This is a platform trial to conduct a series of randomized, double-blind, placebo-controlled trials using common assessments and endpoints in hospitalized adults diagnosed with Coronavirus Disease 2019 (COVID-19). Big Effect Trial (BET) is a proof-of-concept study with the intent of identifying promising treatments to enter a more definitive study. The study will be conducted in up to 70 domestic sites and 5 international sites. The study will compare different investigational therapeutic agents to a common control arm and determine which have relatively large effects. In order to maintain the double blind, each intervention will have a matched placebo. However, the control arm will be shared between interventions and may include participants receiving the matched placebo for a different intervention. The goal is not to determine clear statistical significance for an intervention, but rather to determine which products have clinical data suggestive of efficacy and should be moved quickly into larger studies. Estimates produced from BET will provide an improved basis for designing the larger trial, in terms of sample size and endpoint selection. Products with little indication of efficacy will be dropped on the basis of interim evaluations. In addition, some interventions may be discontinued on the basis of interim futility or efficacy analyses. One or more interventions may be started at any time. The number of interventions enrolling are programmatic decisions and will be based on the number of sites and the pace of enrollment. At the time of enrollment, subjects will be randomized to receive any one of the active arms they are eligible for or placebo. Approximately 200 (100 treatment and 100 shared placebo) subjects will be assigned to each arm entering the platform and a given site will generally have no more than 3 interventions at once. The BET-B stage will evaluate the combination of remdesivir with lenzilumab vs remdesivir with a lenzilumab placebo. The primary objective is to evaluate the clinical efficacy of different investigational therapeutics relative to the control arm in adults hospitalized with COVID-19 according to clinical status (8-point ordinal scale) at Day 8.
Detailed description
This is a platform trial to conduct a series of randomized, double-blind, placebo-controlled trials using common assessments and endpoints in hospitalized adults diagnosed with Coronavirus Disease 2019 (COVID-19). Big Effect Trial (BET) is a proof-of-concept study with the intent of identifying promising treatments to enter a more definitive study. The study will be conducted in up to 70 domestic sites and 5 international sites. The study will compare different investigational therapeutic agents to a common control arm and determine which have relatively large effects. In order to maintain the double blind, each intervention will have a matched placebo. However, the control arm will be shared between interventions and may include participants receiving the matched placebo for a different intervention. The goal is not to determine clear statistical significance for an intervention, but rather to determine which products have clinical data suggestive of efficacy and should be moved quickly into larger studies. Estimates produced from BET will provide an improved basis for designing the larger trial, in terms of sample size and endpoint selection. Products with little indication of efficacy will be dropped on the basis of interim evaluations. In addition, some interventions may be discontinued on the basis of interim futility or efficacy analyses. One or more interventions may be started at any time. The number of interventions enrolling are programmatic decisions and will be based on the number of sites and the pace of enrollment. At the time of enrollment, subjects will be randomized to receive any one of the active arms they are eligible for or placebo. Approximately 200 (100 treatment and 100 shared placebo) subjects will be assigned to each arm entering the platform and a given site will generally have no more than 3 interventions at once. The BET-B stage will evaluate the combination of remdesivir with lenzilumab vs remdesivir with a lenzilumab placebo. Subjects will be assessed daily while hospitalized. Once subjects are discharged from the hospital, they will have a study visit at Days 8, 15, 22, 29, and 60 as an outpatient. The Day 8, Day 22 and Day 60 visits do not have laboratory tests or collection of samples and may be conducted by phone. All subjects will undergo a series of efficacy and safety laboratory assessments. Safety laboratory tests and blood (serum and plasma) research samples and oropharyngeal (OP) swabs will be obtained on Day 1 (prior to study product administration) and Days 3, 5, 8, and 11 while hospitalized. OP swabs (oropharyngeal swabs are preferred, but if these are not obtainable, saliva or nasopharyngeal or nasal swabs may be substituted) and blood research samples plus safety laboratory tests will be collected on Day 15 and 29 if the subject attends an in-person visit or is still hospitalized. However, if infection control considerations or other restrictions prevent the subject from returning to the clinic, Day 15 and 29 visits may be conducted by phone and only clinical data will be obtained. The primary objective is to evaluate the clinical efficacy of different investigational therapeutics relative to the control arm in adults hospitalized with COVID-19 according to clinical status (8-point ordinal scale) at Day 8. The key secondary objectives are to 1) evaluate the clinical efficacy of different investigational therapeutics as assessed by time to recovery compared to the control arm, and 2) to evaluate the proportion of subjects alive and without respiratory failure through Day 29. Contacts: 20-0013 Central Contact Telephone: 1 (301) 7617948 Email: DMIDClinicalTrials@niaid.nih.gov
Interventions
BIOLOGICALLenzilumab
Lenzilumab is a first-in-class recombinant monoclonal antibody targeting soluble human GM-CSF, with potential immunomodulating activity, high binding affinity in the pM range, and 94% specificity to the human germline, which reduces immunogenicity.
OTHERPlacebo
Placebo for lenzilumab is commercially sourced 0.9% sodium chloride.
DRUGRemdesivir
Remdesivir is a single diastereomer monophosphoramidate prodrug designed for the intracellular delivery of a modified adenine nucleoside analog GS-441524.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
1. Admitted to a hospital with symptoms suggestive of Coronavirus Disease 2019 (COVID-19) and requires ongoing medical care. 2. Subject (or legally authorized representative) provides informed consent prior to initiation of any study procedures. 3. Subject (or legally authorized representative) understands and agrees to comply with planned study procedures. 4. Male or non-pregnant female adult \>/= 18 years of age at time of enrollment. 5. Illness of any duration and has laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as determined by polymerase chain reaction (PCR) or other commercial or public health assay (e.g., Nucleic Acid Amplification Test \[NAAT\], antigen test) in any respiratory specimen, or saliva \</=14 days prior to randomization. 6. Illness of any duration, and requiring, just prior to randomization, supplemental oxygen (any flow), mechanical ventilation or Extracorporeal Membrane Oxygenation (ECMO) (ordinal score 5, 6, or 7). 7. Women of childbearing potential must agree to either abstinence or use at least one acceptable method of contraception\* from the time of screening through 5 months post study intraperitoneal (IP) dosing. \* Acceptable methods include barrier contraceptives (condoms or diaphragm) with spermicide, intrauterine devices (IUDs), hormonal contraceptives, oral contraceptive pills, and surgical sterilization. 8. Agrees not to participate in another blinded clinical trial (both pharmacologic and other types of interventions) for the treatment of COVID-19 through Day 29.
Exclusion criteria
1. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 5 times the upper limit of normal. 2. Subjects with a low glomerular filtration rate (eGFR), specifically: 1. Subjects with a glomerular filtration rate (eGFR) 20-30 mL/min are excluded unless in the opinion of the principal investigator (PI), the potential benefit of participation outweighs the potential risk of study participation. 2. All subjects with a glomerular filtration rate (eGFR) \<20 mL/min (including hemodialysis and hemofiltration) are excluded. 3. Pregnancy or breast feeding. 4. Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 72 hours of enrollment. 5. Allergy to any study medication. 6. Received five or more doses of remdesivir prior to screening. 7. Received small molecule tyrosine kinase inhibitors, including Janus kinase (JAK) inhibitors (e.g., baricitinib, ibrutinib, acalabrutinib, imatinib, gefitinib), in the 4 weeks prior to screening. 8. Received monoclonal antibodies targeting cytokines (e.g., tumor necrosis factor (TNF) inhibitors, anti-IL-1 \[e.g., anakinra, canakinumab\], anti-IL-6 \[e.g., tocilizumab, sarilumab, sitlukimab\]), or T-cells (e.g., abatacept) in the 4 weeks prior to screening. 9. Received monoclonal antibodies targeting B-cells (e.g., rituximab, and including any targeting multiple cell lines including B-cells) in the 3 months prior to screening. 10. Received granulocyte-macrophage colony-stimulating factor (GM-CSF) agents (e.g., sargramostim) within 2 months prior to screening. 11. Received other immunosuppressants in the 4 weeks prior to screening and in the judgement of the investigator, the risk of immunosuppression with lenzilumab is larger than the risk of Coronavirus Disease 2019 (COVID-19). 12. Received any live vaccine in the 4 weeks prior to screening. 13. Known active tuberculosis. 14. Known history of Human Immunodeficiency Virus (HIV), Hepatitis B (HBV) or untreated hepatitis C (HCV) infection. 15. History of pulmonary alveolar proteinosis (PAP). 16. Has a malignancy currently receiving immunosuppressive chemotherapy, immunodeficiency, uncontrolled opportunistic infection, or uncontrolled cirrhosis. 17. Has a medical condition that could, in the judgment of the investigator, limit the interpretation and generalizability of trial results. 18. Positive test for influenza virus during the current illness (influenza testing is not required by protocol). 19. Previous participation in an ACTIV-5/Big Effect Trial (BET).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Alive and Without Mechanical Ventilation Through Day 29 in Participants With Baseline Ordinal Score of 5 or 6, C-reactive Protein (CRP)<150mg/L and Age <85 Years | Day 1 through Day 29 | Ordinal scale categories include 7) Hospitalized, on Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) and 8) Death. Mechanical ventilation-free survival was assessed through Day 29, defined as the proportion of participants who had not died nor were hospitalized on invasive mechanical ventilation or ECMO from Day 1 through Day 29. Estimates for the proportions are estimated from a logistic regression model adjusted for baseline dexamethasone, baseline ordinal score, age (continuous), and baseline CRP. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Sustained Recovery in Participants With a Baseline Ordinal Score of 5 or 6, CRP<150mg/L and Age <85 Years | Day 1 through Day 60 | Day of sustained recovery is defined as the first day on which the participant satisfies 1 of the following 3 categories from the clinical status ordinal scale (and does not return to a score of = 4 up to and including Study Day 60): 1) Not hospitalized, no new or increased limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home oxygen, Continuous Positive Airway Pressure (CPAP), or Bilevel Positive Airway Pressure (BiPAP); 3) Hospitalized, not requiring new or increased supplemental oxygen - no longer requires ongoing medical care. |
| Time to Sustained Recovery in Participants With Any Baseline Ordinal Score | Day 1 through Day 60 | Day of sustained recovery is defined as the first day on which the participant satisfies 1 of the following 3 categories from the clinical status ordinal scale (and does not return to a score of = 4 up to and including Study Day 60): 1) Not hospitalized, no new or increased limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home oxygen, CPAP, or BiPAP; 3) Hospitalized, not requiring new or increased supplemental oxygen - no longer requires ongoing medical care. |
| Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | Day 8 | The ordinal scale categories are defined as: 1) Not hospitalized, no new or increased limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home oxygen, CPAP, or BiPAP; 3) Hospitalized, not requiring new or increased supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring new or increased supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring new or increased supplemental oxygen; 6) Hospitalized, requiring new or increased non-invasive ventilation or highflow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death |
| Change From Baseline in C-Reactive Protein (CRP) | Days 1, 3, 5, 8, 11, 15, 29 | Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome. |
| Change From Baseline in D-dimer | Days 1, 3, 5, 8, 11, 15, 29 | Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome. |
| Change From Baseline in Ferritin | Days 1, 3, 5, 8, 11, 15, 29 | Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome. |
| Change From Baseline in Fibrinogen | Days 1, 3, 5, 8, 11, 15, 29 | Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Higher results are better, so a higher positive change from baseline indicates a more favorable outcome. |
| Change From Baseline in Alanine Aminotransferase (ALT) | Days 1, 3, 5, 8, 11, 15, 29 | Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome. |
| Change From Baseline in Aspartate Transaminase (AST) | Days 1, 3, 5, 8, 11, 15, 29 | Blood to evaluate AST was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome. |
| Change From Baseline in Creatinine | Days 1, 3, 5, 8, 11, 15, 29 | Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome. |
| Change From Baseline in International Normalized Ratio (INR) | Days 1, 3, 5, 8, 11, 15, 29 | Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome. |
| Change From Baseline in Hemoglobin | Days 1, 3, 5, 8, 11, 15, 29 | Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Higher results are better, so a higher positive change from baseline indicates a more favorable outcome. |
| Change From Baseline in Platelets Count | Days 1, 3, 5, 8, 11, 15, 29 | Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Higher results are better, so a higher positive change from baseline indicates a more favorable outcome. |
| Change From Baseline in Total Bilirubin | Days 1, 3, 5, 8, 11, 15, 29 | Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome. |
| Change From Baseline in White Blood Cell (WBC) Count | Days 1, 3, 5, 8, 11, 15, 29 | Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Higher results are better, so a higher positive change from baseline indicates a more favorable outcome. |
| Change From Baseline in Neutrophils | Days 1, 3, 5, 8, 11, 15, 29 | Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Higher results are better, so a higher positive change from baseline indicates a more favorable outcome. |
| Change From Baseline in Eosinophils | Days 1, 3, 5, 8, 11, 15, 29 | Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome. |
| Change From Baseline in Basophils | Days 1, 3, 5, 8, 11, 15, 29 | Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome. |
| Change From Baseline in Lymphocytes | Days 1, 3, 5, 8, 11, 15, 29 | Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Higher results are better, so a higher positive change from baseline indicates a more favorable outcome. |
| Change From Baseline in Monocytes | Days 1, 3, 5, 8, 11, 15, 29 | Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome. |
| Number of Participants Reporting Grade 3, 4, or 5 Clinical and/or Laboratory Adverse Events (AEs) | Day 1 through Day 60 | Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening while Grade 5 AEs are those that are fatal. Laboratory results were considered AEs if they were grade 3 or above according to the thresholds in the Division of AIDS (DAIDS) Table for Grading the Severity of Adverse Events. |
| Number of Participants Reporting Serious Adverse Events (SAEs) | Day 1 through Day 60 | An SAE is defined as an AE or suspected adverse reaction that is considered serious if, in the view of either the investigator or the sponsor, it results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. |
| Number of Participants Who Discontinued or Temporarily Suspended Study Treatment | Day 1 through Day 29 | Discontinuation or temporary suspension of study product is defined as any episode of early discontinuation or interruption of study product administration. |
| Duration of Hospitalization | Day 1 through Day 29 | Duration of hospitalization is defined first as the total number of days hospitalized for COVID-19, including readmissions for COVID-19-related reasons. It is also calculated as the total number of days hospitalized, including any readmissions for any reason. |
| Days of Invasive Mechanical Ventilation/Extracorporeal Membrane Oxygenation (ECMO) Use | Day 1 through Day 29 | Duration of invasive ventilation/ECMO was measured in days among participants who required invasive ventilation or died. |
| Days of New Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) Use | Day 1 through Day 29 | Duration of new invasive mechanical ventilation/ECMO use was measured in days among participants not on invasive ventilation/ECMO at baseline who progressed to invasive ventilation/ECMO or died. |
| Days of Non-invasive Ventilation/High Flow Oxygen Use | Day 1 through Day 29 | Duration of non-invasive ventilation or high flow oxygen use was measured in days among participants who required non-invasive ventilation/high flow oxygen, invasive ventilation/ECMO or died. |
| Days of New Non-invasive Ventilation/High Flow Oxygen Use | Day 1 through Day 29 | Duration of new non-invasive ventilation or high flow oxygen use was measured in days among participants not on non-invasive ventilation/high flow oxygen at baseline who progressed to non-invasive ventilation/high flow oxygen, invasive ventilation/ECMO or died. |
| Days of Supplemental Oxygen Use | Day 1 through Day 29 | Duration of supplemental oxygen use was measured in days among participants who required any supplemental oxygen, non-invasive ventilation/high flow oxygen, invasive ventilation/ECMO or died. |
| Number of Participants With New Invasive Mechanical Ventilation / Extracorporeal Membrane Oxygenation (ECMO) Use | Day 1 through Day 29 | New Invasive Mechanical Ventilation / Extracorporeal Membrane Oxygenation (ECMO) Use is defined as participants not on invasive ventilation/ECMO at baseline who progressed to invasive ventilation/ECMO or died during the study. |
| Number of Participants With New Non-invasive Ventilation/High Flow Oxygen Use | Day 1 through Day 29 | New Non-invasive Ventilation/High Flow Oxygen Use is defined as participants in the hospitalized requiring new or increased supplemental oxygen ordinal scale or below at baseline who progressed to noninvasive ventilation/high flow oxygen, invasive ventilation/ECMO or died during the study. |
| Mean Change in Ordinal Scale | Days 1, 3, 5, 8, 11, 15, 22, 29 | The ordinal scale categories are defined as: 1) Not hospitalized, no new or increased limitations on activities;2) Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home oxygen, CPAP, or BiPAP; 3) Hospitalized, not requiring new or increased supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring new or increased supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring new or increased supplemental oxygen; 6) Hospitalized, requiring new or increased non-invasive ventilation or highflow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death. A positive change indicates a worsening and a negative change is an improvement. |
| 14-day Participant Mortality | Day 1 through Day 15 | The mortality rate was determined as the proportion of participants who died by study Day 15. The proportions reported are Kaplan-Meier estimates. |
| 28-day Participant Mortality | Day 1 through Day 29 | The mortality rate was determined as the proportion of participants who died by study Day 29. The proportions reported are Kaplan-Meier estimates. |
| Proportion of Participants Alive and Without Mechanical Ventilation Through Day 29 in Participants With Any Baseline Ordinal Score | Day 1 through Day 29 | Mechanical ventilation-free survival was assessed through Day 29, defined as the proportion of participants who had not died nor were hospitalized on invasive mechanical ventilation or ECMO from Day 1 through Day 29. Estimates for the proportions are estimated from a logistic regression model adjusted for baseline dexamethasone, baseline ordinal score, age (continuous), and baseline CRP. |
| Proportion of Participants Not Meeting Criteria for One of Two Ordinal Scale Categories at Day 29 | Day 29 | Ordinal scale categories include 7) Hospitalized, on Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) and 8) Death. Defined as the proportion of participants who were alive and were not hospitalized on invasive mechanical ventilation or ECMO at the Day 29 visit. |
| Time to an Improvement of One Category From Baseline Using an Ordinal Scale | Day 1 through Day 60 | The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Not hospitalized, no new or increased limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home oxygen, CPAP, or BiPAP; 3) Hospitalized, not requiring new or increased supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring new or increased supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring new or increased supplemental oxygen; 6) Hospitalized, requiring new or increased noninvasive ventilation or high-flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death. |
| Time to an Improvement of Two Categories From Baseline Using an Ordinal Scale | Day 1 through Day 60 | The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Not hospitalized, no new or increased limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home oxygen, CPAP, or BiPAP; 3) Hospitalized, not requiring new or increased supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring new or increased supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring new or increased supplemental oxygen; 6) Hospitalized, requiring new or increased noninvasive ventilation or high-flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death. |
| Time to Death | Day 1 through Day 29 | The time to death from study Day 1 to study Day 29, measured in days. The times reported are Kaplan-Meier estimates. |
| 59-day Participant Mortality | Day 1 through Day 60 | The mortality rate was determined as the proportion of participants who died by study Day 60. The proportions reported are Kaplan-Meier estimates. |
Countries
South Korea, United States
Participant flow
Recruitment details
Participants were male and non-pregnant female adults who were 18 years of age or older and hospitalized with COVID-19. Participants were enrolled between 23OCT2020 and 09JAN2022.
Participants by arm
| Arm | Count |
|---|---|
| Remdesivir + Lenzilumab 200-mg intravenous (IV) remdesivir loading dose on Day 1, followed by a 100-mg once-daily IV maintenance dose up to a 10-day total course while hospitalized and 600-mg IV lenzilumab infusion every 8 hours starting on Day 1 for a total of 3 doses. | 272 |
| Remdesivir + Placebo 200-mg intravenous (IV) remdesivir loading dose on Day 1, followed by a 100-mg once-daily IV maintenance dose up to a 10-day total course while hospitalized and 600-mg IV lenzilumab placebo infusion every 8 hours starting on Day 1 for a total of 3 doses. | 255 |
| Total | 527 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 31 | 38 |
| Overall Study | Lost to Follow-up | 16 | 13 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | RANDOMIZED BUT NOT DOSED | 2 | 4 |
| Overall Study | RECEIVED PROHIBITED CONCOMITANT THERAPY | 1 | 0 |
| Overall Study | TECHNICAL DIFFICULTIES, NOT ENOUGH STUDY DRUG ON SITE | 1 | 0 |
| Overall Study | TRANSITION TO COMFORT CARE/HOSPICE | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 3 |
| Overall Study | WITHDRAWAL OF CONSENT BEFORE PRODUCT ADMINISTRATION | 1 | 1 |
Baseline characteristics
| Characteristic | Remdesivir + Lenzilumab | Remdesivir + Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 68 Participants | 69 Participants | 137 Participants |
| Age, Categorical Between 18 and 65 years | 204 Participants | 186 Participants | 390 Participants |
| Age, Continuous | 55.7 years STANDARD_DEVIATION 13.9 | 55.1 years STANDARD_DEVIATION 14.3 | 55.4 years STANDARD_DEVIATION 14.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 42 Participants | 54 Participants | 96 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 229 Participants | 200 Participants | 429 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 10 Participants | 14 Participants | 24 Participants |
| Race (NIH/OMB) Black or African American | 51 Participants | 49 Participants | 100 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 12 Participants | 16 Participants | 28 Participants |
| Race (NIH/OMB) White | 194 Participants | 175 Participants | 369 Participants |
| Region of Enrollment South Korea | 4 participants | 6 participants | 10 participants |
| Region of Enrollment United States | 268 participants | 249 participants | 517 participants |
| Sex: Female, Male Female | 91 Participants | 88 Participants | 179 Participants |
| Sex: Female, Male Male | 181 Participants | 167 Participants | 348 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 31 / 272 | 38 / 255 |
| other Total, other adverse events | 41 / 264 | 54 / 250 |
| serious Total, serious adverse events | 76 / 264 | 81 / 250 |
Outcome results
Primary
Proportion of Participants Alive and Without Mechanical Ventilation Through Day 29 in Participants With Baseline Ordinal Score of 5 or 6, C-reactive Protein (CRP)<150mg/L and Age <85 Years
Ordinal scale categories include 7) Hospitalized, on Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) and 8) Death. Mechanical ventilation-free survival was assessed through Day 29, defined as the proportion of participants who had not died nor were hospitalized on invasive mechanical ventilation or ECMO from Day 1 through Day 29. Estimates for the proportions are estimated from a logistic regression model adjusted for baseline dexamethasone, baseline ordinal score, age (continuous), and baseline CRP.
Time frame: Day 1 through Day 29
Population: The primary subgroup population includes all randomized participants with a baseline ordinal score of 5 or 6, CRP\<150 mg/L at baseline, and age\<85 years.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Remdesivir + Lenzilumab | Proportion of Participants Alive and Without Mechanical Ventilation Through Day 29 in Participants With Baseline Ordinal Score of 5 or 6, C-reactive Protein (CRP)<150mg/L and Age <85 Years | 0.85 Proportion of participants |
| Remdesivir + Placebo | Proportion of Participants Alive and Without Mechanical Ventilation Through Day 29 in Participants With Baseline Ordinal Score of 5 or 6, C-reactive Protein (CRP)<150mg/L and Age <85 Years | 0.84 Proportion of participants |
Comparison: Odds ratio, CI, and p-value estimated from a logistic regression model adjusted for baseline dexamethasone use, baseline OS, age (continuous), and baseline CRP. Missing data imputed using the 3-stage multiple imputation procedure described in the statistical analysis plan.p-value: 0.69195% CI: [0.63, 2.02]Regression, Logistic
Secondary
14-day Participant Mortality
The mortality rate was determined as the proportion of participants who died by study Day 15. The proportions reported are Kaplan-Meier estimates.
Time frame: Day 1 through Day 15
Population: The safety population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies, classified by their actual treatment assignment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Remdesivir + Lenzilumab | 14-day Participant Mortality | 0.05 Proportion of participants |
| Remdesivir + Placebo | 14-day Participant Mortality | 0.07 Proportion of participants |
Secondary
28-day Participant Mortality
The mortality rate was determined as the proportion of participants who died by study Day 29. The proportions reported are Kaplan-Meier estimates.
Time frame: Day 1 through Day 29
Population: The safety population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies, classified by their actual treatment assignment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Remdesivir + Lenzilumab | 28-day Participant Mortality | 0.10 Proportion of participants |
| Remdesivir + Placebo | 28-day Participant Mortality | 0.12 Proportion of participants |
Secondary
59-day Participant Mortality
The mortality rate was determined as the proportion of participants who died by study Day 60. The proportions reported are Kaplan-Meier estimates.
Time frame: Day 1 through Day 60
Population: The safety population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies, classified by their actual treatment assignment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Remdesivir + Lenzilumab | 59-day Participant Mortality | 0.12 Proportion of participants |
| Remdesivir + Placebo | 59-day Participant Mortality | 0.16 Proportion of participants |
Secondary
Change From Baseline in Alanine Aminotransferase (ALT)
Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome.
Time frame: Days 1, 3, 5, 8, 11, 15, 29
Population: The safety population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies with available data at baseline and post baseline assessment time point, analyzed as treated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Remdesivir + Lenzilumab | Change From Baseline in Alanine Aminotransferase (ALT) | Day 3 | 6.4 U/L | Standard Deviation 42.6 |
| Remdesivir + Lenzilumab | Change From Baseline in Alanine Aminotransferase (ALT) | Day 5 | 29.3 U/L | Standard Deviation 146.8 |
| Remdesivir + Lenzilumab | Change From Baseline in Alanine Aminotransferase (ALT) | Day 8 | 19.7 U/L | Standard Deviation 108.8 |
| Remdesivir + Lenzilumab | Change From Baseline in Alanine Aminotransferase (ALT) | Day 11 | 9.8 U/L | Standard Deviation 71.6 |
| Remdesivir + Lenzilumab | Change From Baseline in Alanine Aminotransferase (ALT) | Day 15 | 15.7 U/L | Standard Deviation 71.5 |
| Remdesivir + Lenzilumab | Change From Baseline in Alanine Aminotransferase (ALT) | Day 29 | 17.3 U/L | Standard Deviation 158.5 |
| Remdesivir + Placebo | Change From Baseline in Alanine Aminotransferase (ALT) | Day 15 | -2.5 U/L | Standard Deviation 48.5 |
| Remdesivir + Placebo | Change From Baseline in Alanine Aminotransferase (ALT) | Day 3 | 4.0 U/L | Standard Deviation 34 |
| Remdesivir + Placebo | Change From Baseline in Alanine Aminotransferase (ALT) | Day 11 | 7.8 U/L | Standard Deviation 83.4 |
| Remdesivir + Placebo | Change From Baseline in Alanine Aminotransferase (ALT) | Day 5 | 29.7 U/L | Standard Deviation 189.1 |
| Remdesivir + Placebo | Change From Baseline in Alanine Aminotransferase (ALT) | Day 29 | 12.4 U/L | Standard Deviation 256 |
| Remdesivir + Placebo | Change From Baseline in Alanine Aminotransferase (ALT) | Day 8 | 9.2 U/L | Standard Deviation 108.3 |
Secondary
Change From Baseline in Aspartate Transaminase (AST)
Blood to evaluate AST was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome.
Time frame: Days 1, 3, 5, 8, 11, 15, 29
Population: The safety population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies with available data at baseline and post baseline assessment time point, analyzed as treated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Remdesivir + Lenzilumab | Change From Baseline in Aspartate Transaminase (AST) | Day 3 | -5.9 U/L | Standard Deviation 41.2 |
| Remdesivir + Lenzilumab | Change From Baseline in Aspartate Transaminase (AST) | Day 5 | -1.0 U/L | Standard Deviation 64.5 |
| Remdesivir + Lenzilumab | Change From Baseline in Aspartate Transaminase (AST) | Day 8 | -17.7 U/L | Standard Deviation 46.6 |
| Remdesivir + Lenzilumab | Change From Baseline in Aspartate Transaminase (AST) | Day 11 | -16.6 U/L | Standard Deviation 77.7 |
| Remdesivir + Lenzilumab | Change From Baseline in Aspartate Transaminase (AST) | Day 15 | -9.6 U/L | Standard Deviation 55.7 |
| Remdesivir + Lenzilumab | Change From Baseline in Aspartate Transaminase (AST) | Day 29 | -9.6 U/L | Standard Deviation 51.8 |
| Remdesivir + Placebo | Change From Baseline in Aspartate Transaminase (AST) | Day 15 | -21.0 U/L | Standard Deviation 40 |
| Remdesivir + Placebo | Change From Baseline in Aspartate Transaminase (AST) | Day 3 | -7.5 U/L | Standard Deviation 31.7 |
| Remdesivir + Placebo | Change From Baseline in Aspartate Transaminase (AST) | Day 11 | 1.5 U/L | Standard Deviation 194.7 |
| Remdesivir + Placebo | Change From Baseline in Aspartate Transaminase (AST) | Day 5 | 12.2 U/L | Standard Deviation 276.7 |
| Remdesivir + Placebo | Change From Baseline in Aspartate Transaminase (AST) | Day 29 | 17.4 U/L | Standard Deviation 404.9 |
| Remdesivir + Placebo | Change From Baseline in Aspartate Transaminase (AST) | Day 8 | -1.8 U/L | Standard Deviation 243 |
Secondary
Change From Baseline in Basophils
Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome.
Time frame: Days 1, 3, 5, 8, 11, 15, 29
Population: The safety population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies with available data at baseline and post baseline assessment time point, analyzed as treated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Remdesivir + Lenzilumab | Change From Baseline in Basophils | Day 3 | 0.01003 10^9 cells/L | Standard Deviation 0.06346 |
| Remdesivir + Lenzilumab | Change From Baseline in Basophils | Day 5 | 0.00944 10^9 cells/L | Standard Deviation 0.05689 |
| Remdesivir + Lenzilumab | Change From Baseline in Basophils | Day 8 | 0.00680 10^9 cells/L | Standard Deviation 0.04749 |
| Remdesivir + Lenzilumab | Change From Baseline in Basophils | Day 11 | 0.03623 10^9 cells/L | Standard Deviation 0.07673 |
| Remdesivir + Lenzilumab | Change From Baseline in Basophils | Day 15 | 0.04123 10^9 cells/L | Standard Deviation 0.06928 |
| Remdesivir + Lenzilumab | Change From Baseline in Basophils | Day 29 | 0.04311 10^9 cells/L | Standard Deviation 0.05582 |
| Remdesivir + Placebo | Change From Baseline in Basophils | Day 15 | 0.02566 10^9 cells/L | Standard Deviation 0.04527 |
| Remdesivir + Placebo | Change From Baseline in Basophils | Day 3 | 0.01082 10^9 cells/L | Standard Deviation 0.04173 |
| Remdesivir + Placebo | Change From Baseline in Basophils | Day 11 | 0.02402 10^9 cells/L | Standard Deviation 0.04017 |
| Remdesivir + Placebo | Change From Baseline in Basophils | Day 5 | 0.01103 10^9 cells/L | Standard Deviation 0.02979 |
| Remdesivir + Placebo | Change From Baseline in Basophils | Day 29 | 0.03504 10^9 cells/L | Standard Deviation 0.06657 |
| Remdesivir + Placebo | Change From Baseline in Basophils | Day 8 | 0.01679 10^9 cells/L | Standard Deviation 0.03481 |
Secondary
Change From Baseline in C-Reactive Protein (CRP)
Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome.
Time frame: Days 1, 3, 5, 8, 11, 15, 29
Population: The safety population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies with available data at baseline and post baseline assessment time point, analyzed as treated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Remdesivir + Lenzilumab | Change From Baseline in C-Reactive Protein (CRP) | Day 3 | -56.006 mg/L | Standard Deviation 111.701 |
| Remdesivir + Lenzilumab | Change From Baseline in C-Reactive Protein (CRP) | Day 5 | -62.300 mg/L | Standard Deviation 125.644 |
| Remdesivir + Lenzilumab | Change From Baseline in C-Reactive Protein (CRP) | Day 8 | -73.118 mg/L | Standard Deviation 162.628 |
| Remdesivir + Lenzilumab | Change From Baseline in C-Reactive Protein (CRP) | Day 11 | -33.713 mg/L | Standard Deviation 112.26 |
| Remdesivir + Lenzilumab | Change From Baseline in C-Reactive Protein (CRP) | Day 15 | -48.847 mg/L | Standard Deviation 95.126 |
| Remdesivir + Lenzilumab | Change From Baseline in C-Reactive Protein (CRP) | Day 29 | -65.175 mg/L | Standard Deviation 82.724 |
| Remdesivir + Placebo | Change From Baseline in C-Reactive Protein (CRP) | Day 15 | -61.548 mg/L | Standard Deviation 75 |
| Remdesivir + Placebo | Change From Baseline in C-Reactive Protein (CRP) | Day 3 | -41.259 mg/L | Standard Deviation 67.158 |
| Remdesivir + Placebo | Change From Baseline in C-Reactive Protein (CRP) | Day 11 | -48.647 mg/L | Standard Deviation 108.481 |
| Remdesivir + Placebo | Change From Baseline in C-Reactive Protein (CRP) | Day 5 | -36.272 mg/L | Standard Deviation 112.545 |
| Remdesivir + Placebo | Change From Baseline in C-Reactive Protein (CRP) | Day 29 | -70.728 mg/L | Standard Deviation 73.967 |
| Remdesivir + Placebo | Change From Baseline in C-Reactive Protein (CRP) | Day 8 | -49.618 mg/L | Standard Deviation 88.759 |
Secondary
Change From Baseline in Creatinine
Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome.
Time frame: Days 1, 3, 5, 8, 11, 15, 29
Population: The safety population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies with available data at baseline and post baseline assessment time point, analyzed as treated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Remdesivir + Lenzilumab | Change From Baseline in Creatinine | Day 3 | -0.060 mg/dL | Standard Deviation 0.134 |
| Remdesivir + Lenzilumab | Change From Baseline in Creatinine | Day 5 | -0.053 mg/dL | Standard Deviation 0.307 |
| Remdesivir + Lenzilumab | Change From Baseline in Creatinine | Day 8 | -0.020 mg/dL | Standard Deviation 0.672 |
| Remdesivir + Lenzilumab | Change From Baseline in Creatinine | Day 11 | 0.012 mg/dL | Standard Deviation 0.715 |
| Remdesivir + Lenzilumab | Change From Baseline in Creatinine | Day 15 | -0.037 mg/dL | Standard Deviation 0.321 |
| Remdesivir + Lenzilumab | Change From Baseline in Creatinine | Day 29 | 0.049 mg/dL | Standard Deviation 0.612 |
| Remdesivir + Placebo | Change From Baseline in Creatinine | Day 15 | 0.188 mg/dL | Standard Deviation 0.868 |
| Remdesivir + Placebo | Change From Baseline in Creatinine | Day 3 | -0.028 mg/dL | Standard Deviation 0.215 |
| Remdesivir + Placebo | Change From Baseline in Creatinine | Day 11 | 0.210 mg/dL | Standard Deviation 0.875 |
| Remdesivir + Placebo | Change From Baseline in Creatinine | Day 5 | -0.019 mg/dL | Standard Deviation 0.392 |
| Remdesivir + Placebo | Change From Baseline in Creatinine | Day 29 | 0.155 mg/dL | Standard Deviation 0.986 |
| Remdesivir + Placebo | Change From Baseline in Creatinine | Day 8 | -0.038 mg/dL | Standard Deviation 0.379 |
Secondary
Change From Baseline in D-dimer
Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome.
Time frame: Days 1, 3, 5, 8, 11, 15, 29
Population: The safety population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies with available data at baseline and post baseline assessment time point, analyzed as treated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Remdesivir + Lenzilumab | Change From Baseline in D-dimer | Day 3 | 496.548 µg/L fibrinogen equivalent units (FEU) | Standard Deviation 5714.241 |
| Remdesivir + Lenzilumab | Change From Baseline in D-dimer | Day 5 | 1779.571 µg/L fibrinogen equivalent units (FEU) | Standard Deviation 7877.791 |
| Remdesivir + Lenzilumab | Change From Baseline in D-dimer | Day 8 | 2104.619 µg/L fibrinogen equivalent units (FEU) | Standard Deviation 8930.666 |
| Remdesivir + Lenzilumab | Change From Baseline in D-dimer | Day 11 | 1937.748 µg/L fibrinogen equivalent units (FEU) | Standard Deviation 9253.749 |
| Remdesivir + Lenzilumab | Change From Baseline in D-dimer | Day 15 | 184.022 µg/L fibrinogen equivalent units (FEU) | Standard Deviation 6162.04 |
| Remdesivir + Lenzilumab | Change From Baseline in D-dimer | Day 29 | -328.954 µg/L fibrinogen equivalent units (FEU) | Standard Deviation 5271.468 |
| Remdesivir + Placebo | Change From Baseline in D-dimer | Day 15 | 422.458 µg/L fibrinogen equivalent units (FEU) | Standard Deviation 6104.354 |
| Remdesivir + Placebo | Change From Baseline in D-dimer | Day 3 | 994.162 µg/L fibrinogen equivalent units (FEU) | Standard Deviation 5752.139 |
| Remdesivir + Placebo | Change From Baseline in D-dimer | Day 11 | 1304.639 µg/L fibrinogen equivalent units (FEU) | Standard Deviation 6733.679 |
| Remdesivir + Placebo | Change From Baseline in D-dimer | Day 5 | 2704.873 µg/L fibrinogen equivalent units (FEU) | Standard Deviation 11751.741 |
| Remdesivir + Placebo | Change From Baseline in D-dimer | Day 29 | -736.771 µg/L fibrinogen equivalent units (FEU) | Standard Deviation 4978.655 |
| Remdesivir + Placebo | Change From Baseline in D-dimer | Day 8 | 1544.558 µg/L fibrinogen equivalent units (FEU) | Standard Deviation 13145.089 |
Secondary
Change From Baseline in Eosinophils
Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome.
Time frame: Days 1, 3, 5, 8, 11, 15, 29
Population: The safety population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies with available data at baseline and post baseline assessment time point, analyzed as treated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Remdesivir + Lenzilumab | Change From Baseline in Eosinophils | Day 3 | 0.00234 10^9 cells/L | Standard Deviation 0.05634 |
| Remdesivir + Lenzilumab | Change From Baseline in Eosinophils | Day 5 | 0.03413 10^9 cells/L | Standard Deviation 0.11473 |
| Remdesivir + Lenzilumab | Change From Baseline in Eosinophils | Day 8 | 0.08446 10^9 cells/L | Standard Deviation 0.113 |
| Remdesivir + Lenzilumab | Change From Baseline in Eosinophils | Day 11 | 0.19746 10^9 cells/L | Standard Deviation 0.40542 |
| Remdesivir + Lenzilumab | Change From Baseline in Eosinophils | Day 15 | 0.21128 10^9 cells/L | Standard Deviation 0.208 |
| Remdesivir + Lenzilumab | Change From Baseline in Eosinophils | Day 29 | 0.32429 10^9 cells/L | Standard Deviation 0.31412 |
| Remdesivir + Placebo | Change From Baseline in Eosinophils | Day 15 | 0.14547 10^9 cells/L | Standard Deviation 0.13429 |
| Remdesivir + Placebo | Change From Baseline in Eosinophils | Day 3 | 0.00298 10^9 cells/L | Standard Deviation 0.06616 |
| Remdesivir + Placebo | Change From Baseline in Eosinophils | Day 11 | 0.10947 10^9 cells/L | Standard Deviation 0.1444 |
| Remdesivir + Placebo | Change From Baseline in Eosinophils | Day 5 | 0.02668 10^9 cells/L | Standard Deviation 0.06469 |
| Remdesivir + Placebo | Change From Baseline in Eosinophils | Day 29 | 0.25893 10^9 cells/L | Standard Deviation 0.26106 |
| Remdesivir + Placebo | Change From Baseline in Eosinophils | Day 8 | 0.05383 10^9 cells/L | Standard Deviation 0.14607 |
Secondary
Change From Baseline in Ferritin
Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome.
Time frame: Days 1, 3, 5, 8, 11, 15, 29
Population: The safety population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies with available data at baseline and post baseline assessment time point, analyzed as treated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Remdesivir + Lenzilumab | Change From Baseline in Ferritin | Day 3 | -156.894 µg/L | Standard Deviation 1248.855 |
| Remdesivir + Lenzilumab | Change From Baseline in Ferritin | Day 5 | -303.466 µg/L | Standard Deviation 1400.684 |
| Remdesivir + Lenzilumab | Change From Baseline in Ferritin | Day 8 | -494.266 µg/L | Standard Deviation 1042.361 |
| Remdesivir + Lenzilumab | Change From Baseline in Ferritin | Day 11 | -453.304 µg/L | Standard Deviation 1209.069 |
| Remdesivir + Lenzilumab | Change From Baseline in Ferritin | Day 15 | -304.447 µg/L | Standard Deviation 1013.592 |
| Remdesivir + Lenzilumab | Change From Baseline in Ferritin | Day 29 | -645.899 µg/L | Standard Deviation 1246.98 |
| Remdesivir + Placebo | Change From Baseline in Ferritin | Day 15 | -552.903 µg/L | Standard Deviation 907.992 |
| Remdesivir + Placebo | Change From Baseline in Ferritin | Day 3 | -204.033 µg/L | Standard Deviation 584.563 |
| Remdesivir + Placebo | Change From Baseline in Ferritin | Day 11 | -426.838 µg/L | Standard Deviation 1166.825 |
| Remdesivir + Placebo | Change From Baseline in Ferritin | Day 5 | -254.803 µg/L | Standard Deviation 1396.688 |
| Remdesivir + Placebo | Change From Baseline in Ferritin | Day 29 | -839.410 µg/L | Standard Deviation 1002.701 |
| Remdesivir + Placebo | Change From Baseline in Ferritin | Day 8 | -403.031 µg/L | Standard Deviation 889.021 |
Secondary
Change From Baseline in Fibrinogen
Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Higher results are better, so a higher positive change from baseline indicates a more favorable outcome.
Time frame: Days 1, 3, 5, 8, 11, 15, 29
Population: The safety population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies with available data at baseline and post baseline assessment time point, analyzed as treated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Remdesivir + Lenzilumab | Change From Baseline in Fibrinogen | Day 3 | -90.5 mg/dL | Standard Deviation 109.1 |
| Remdesivir + Lenzilumab | Change From Baseline in Fibrinogen | Day 5 | -94.3 mg/dL | Standard Deviation 415.2 |
| Remdesivir + Lenzilumab | Change From Baseline in Fibrinogen | Day 8 | -126.6 mg/dL | Standard Deviation 200.5 |
| Remdesivir + Lenzilumab | Change From Baseline in Fibrinogen | Day 11 | -47.8 mg/dL | Standard Deviation 238.4 |
| Remdesivir + Lenzilumab | Change From Baseline in Fibrinogen | Day 15 | -53.4 mg/dL | Standard Deviation 229.6 |
| Remdesivir + Lenzilumab | Change From Baseline in Fibrinogen | Day 29 | -145.7 mg/dL | Standard Deviation 177.2 |
| Remdesivir + Placebo | Change From Baseline in Fibrinogen | Day 15 | -70.0 mg/dL | Standard Deviation 208.1 |
| Remdesivir + Placebo | Change From Baseline in Fibrinogen | Day 3 | -90.3 mg/dL | Standard Deviation 121.8 |
| Remdesivir + Placebo | Change From Baseline in Fibrinogen | Day 11 | -83.5 mg/dL | Standard Deviation 260.9 |
| Remdesivir + Placebo | Change From Baseline in Fibrinogen | Day 5 | -104.9 mg/dL | Standard Deviation 171.6 |
| Remdesivir + Placebo | Change From Baseline in Fibrinogen | Day 29 | -118.9 mg/dL | Standard Deviation 191.4 |
| Remdesivir + Placebo | Change From Baseline in Fibrinogen | Day 8 | -120.8 mg/dL | Standard Deviation 208.7 |
Secondary
Change From Baseline in Hemoglobin
Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Higher results are better, so a higher positive change from baseline indicates a more favorable outcome.
Time frame: Days 1, 3, 5, 8, 11, 15, 29
Population: The safety population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies with available data at baseline and post baseline assessment time point, analyzed as treated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Remdesivir + Lenzilumab | Change From Baseline in Hemoglobin | Day 29 | -1.27 g/dL | Standard Deviation 2.24 |
| Remdesivir + Lenzilumab | Change From Baseline in Hemoglobin | Day 3 | -0.27 g/dL | Standard Deviation 0.94 |
| Remdesivir + Lenzilumab | Change From Baseline in Hemoglobin | Day 5 | -0.31 g/dL | Standard Deviation 1.1 |
| Remdesivir + Lenzilumab | Change From Baseline in Hemoglobin | Day 8 | -0.50 g/dL | Standard Deviation 1.38 |
| Remdesivir + Lenzilumab | Change From Baseline in Hemoglobin | Day 11 | -1.03 g/dL | Standard Deviation 1.54 |
| Remdesivir + Lenzilumab | Change From Baseline in Hemoglobin | Day 15 | -1.22 g/dL | Standard Deviation 1.68 |
| Remdesivir + Placebo | Change From Baseline in Hemoglobin | Day 15 | -1.28 g/dL | Standard Deviation 1.93 |
| Remdesivir + Placebo | Change From Baseline in Hemoglobin | Day 29 | -1.21 g/dL | Standard Deviation 2.06 |
| Remdesivir + Placebo | Change From Baseline in Hemoglobin | Day 11 | -0.99 g/dL | Standard Deviation 1.79 |
| Remdesivir + Placebo | Change From Baseline in Hemoglobin | Day 3 | -0.20 g/dL | Standard Deviation 0.99 |
| Remdesivir + Placebo | Change From Baseline in Hemoglobin | Day 8 | -0.48 g/dL | Standard Deviation 1.29 |
| Remdesivir + Placebo | Change From Baseline in Hemoglobin | Day 5 | -0.34 g/dL | Standard Deviation 1.13 |
Secondary
Change From Baseline in International Normalized Ratio (INR)
Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome.
Time frame: Days 1, 3, 5, 8, 11, 15, 29
Population: The safety population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies with available data at baseline and post baseline assessment time point, analyzed as treated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Remdesivir + Lenzilumab | Change From Baseline in International Normalized Ratio (INR) | Day 5 | -0.00790 Ratio | Standard Deviation 0.96495 |
| Remdesivir + Lenzilumab | Change From Baseline in International Normalized Ratio (INR) | Day 8 | -0.07588 Ratio | Standard Deviation 1.1879 |
| Remdesivir + Lenzilumab | Change From Baseline in International Normalized Ratio (INR) | Day 11 | 0.03758 Ratio | Standard Deviation 0.23576 |
| Remdesivir + Lenzilumab | Change From Baseline in International Normalized Ratio (INR) | Day 15 | -0.01725 Ratio | Standard Deviation 0.2034 |
| Remdesivir + Lenzilumab | Change From Baseline in International Normalized Ratio (INR) | Day 29 | -0.08386 Ratio | Standard Deviation 0.16724 |
| Remdesivir + Lenzilumab | Change From Baseline in International Normalized Ratio (INR) | Day 3 | 0.01352 Ratio | Standard Deviation 0.14308 |
| Remdesivir + Placebo | Change From Baseline in International Normalized Ratio (INR) | Day 29 | 0.07535 Ratio | Standard Deviation 1.12891 |
| Remdesivir + Placebo | Change From Baseline in International Normalized Ratio (INR) | Day 5 | 0.10552 Ratio | Standard Deviation 0.46849 |
| Remdesivir + Placebo | Change From Baseline in International Normalized Ratio (INR) | Day 15 | -0.00704 Ratio | Standard Deviation 0.19225 |
| Remdesivir + Placebo | Change From Baseline in International Normalized Ratio (INR) | Day 8 | 0.13077 Ratio | Standard Deviation 0.96702 |
| Remdesivir + Placebo | Change From Baseline in International Normalized Ratio (INR) | Day 3 | 0.05065 Ratio | Standard Deviation 0.18246 |
| Remdesivir + Placebo | Change From Baseline in International Normalized Ratio (INR) | Day 11 | 0.06652 Ratio | Standard Deviation 0.23513 |
Secondary
Change From Baseline in Lymphocytes
Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Higher results are better, so a higher positive change from baseline indicates a more favorable outcome.
Time frame: Days 1, 3, 5, 8, 11, 15, 29
Population: The safety population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies with available data at baseline and post baseline assessment time point, analyzed as treated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Remdesivir + Lenzilumab | Change From Baseline in Lymphocytes | Day 3 | 0.4191 10^9 cells/L | Standard Deviation 1.1325 |
| Remdesivir + Lenzilumab | Change From Baseline in Lymphocytes | Day 5 | 0.4585 10^9 cells/L | Standard Deviation 0.782 |
| Remdesivir + Lenzilumab | Change From Baseline in Lymphocytes | Day 8 | 0.6283 10^9 cells/L | Standard Deviation 1.1126 |
| Remdesivir + Lenzilumab | Change From Baseline in Lymphocytes | Day 11 | 1.0750 10^9 cells/L | Standard Deviation 3.8905 |
| Remdesivir + Lenzilumab | Change From Baseline in Lymphocytes | Day 15 | 0.7693 10^9 cells/L | Standard Deviation 0.7193 |
| Remdesivir + Lenzilumab | Change From Baseline in Lymphocytes | Day 29 | 0.8496 10^9 cells/L | Standard Deviation 0.6764 |
| Remdesivir + Placebo | Change From Baseline in Lymphocytes | Day 15 | 0.5923 10^9 cells/L | Standard Deviation 0.6609 |
| Remdesivir + Placebo | Change From Baseline in Lymphocytes | Day 3 | 0.2191 10^9 cells/L | Standard Deviation 0.7106 |
| Remdesivir + Placebo | Change From Baseline in Lymphocytes | Day 11 | 0.3911 10^9 cells/L | Standard Deviation 0.7718 |
| Remdesivir + Placebo | Change From Baseline in Lymphocytes | Day 5 | 0.2772 10^9 cells/L | Standard Deviation 0.5947 |
| Remdesivir + Placebo | Change From Baseline in Lymphocytes | Day 29 | 0.7451 10^9 cells/L | Standard Deviation 0.9669 |
| Remdesivir + Placebo | Change From Baseline in Lymphocytes | Day 8 | 0.2002 10^9 cells/L | Standard Deviation 1.1396 |
Secondary
Change From Baseline in Monocytes
Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome.
Time frame: Days 1, 3, 5, 8, 11, 15, 29
Population: The safety population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies with available data at baseline and post baseline assessment time point, analyzed as treated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Remdesivir + Lenzilumab | Change From Baseline in Monocytes | Day 15 | 0.3195 10^9 cells/L | Standard Deviation 0.5866 |
| Remdesivir + Lenzilumab | Change From Baseline in Monocytes | Day 5 | 0.3012 10^9 cells/L | Standard Deviation 1.0631 |
| Remdesivir + Lenzilumab | Change From Baseline in Monocytes | Day 8 | 0.4774 10^9 cells/L | Standard Deviation 1.3914 |
| Remdesivir + Lenzilumab | Change From Baseline in Monocytes | Day 11 | 0.6291 10^9 cells/L | Standard Deviation 1.3902 |
| Remdesivir + Lenzilumab | Change From Baseline in Monocytes | Day 29 | 0.1079 10^9 cells/L | Standard Deviation 0.3481 |
| Remdesivir + Lenzilumab | Change From Baseline in Monocytes | Day 3 | 0.2490 10^9 cells/L | Standard Deviation 1.3094 |
| Remdesivir + Placebo | Change From Baseline in Monocytes | Day 29 | 0.0820 10^9 cells/L | Standard Deviation 0.5578 |
| Remdesivir + Placebo | Change From Baseline in Monocytes | Day 3 | 0.1750 10^9 cells/L | Standard Deviation 0.6263 |
| Remdesivir + Placebo | Change From Baseline in Monocytes | Day 11 | 0.2865 10^9 cells/L | Standard Deviation 0.7489 |
| Remdesivir + Placebo | Change From Baseline in Monocytes | Day 5 | 0.1275 10^9 cells/L | Standard Deviation 0.4584 |
| Remdesivir + Placebo | Change From Baseline in Monocytes | Day 15 | 0.3074 10^9 cells/L | Standard Deviation 0.8821 |
| Remdesivir + Placebo | Change From Baseline in Monocytes | Day 8 | 0.1794 10^9 cells/L | Standard Deviation 0.5609 |
Secondary
Change From Baseline in Neutrophils
Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Higher results are better, so a higher positive change from baseline indicates a more favorable outcome.
Time frame: Days 1, 3, 5, 8, 11, 15, 29
Population: The safety population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies with available data at baseline and post baseline assessment time point, analyzed as treated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Remdesivir + Lenzilumab | Change From Baseline in Neutrophils | Day 3 | 0.4146 10^9 cells/L | Standard Deviation 2.7458 |
| Remdesivir + Lenzilumab | Change From Baseline in Neutrophils | Day 5 | 1.8626 10^9 cells/L | Standard Deviation 4.3986 |
| Remdesivir + Lenzilumab | Change From Baseline in Neutrophils | Day 8 | 4.2520 10^9 cells/L | Standard Deviation 4.7959 |
| Remdesivir + Lenzilumab | Change From Baseline in Neutrophils | Day 11 | 5.3638 10^9 cells/L | Standard Deviation 6.4333 |
| Remdesivir + Lenzilumab | Change From Baseline in Neutrophils | Day 15 | 1.8136 10^9 cells/L | Standard Deviation 5.8546 |
| Remdesivir + Lenzilumab | Change From Baseline in Neutrophils | Day 29 | -2.0352 10^9 cells/L | Standard Deviation 4.3887 |
| Remdesivir + Placebo | Change From Baseline in Neutrophils | Day 15 | 0.6347 10^9 cells/L | Standard Deviation 4.758 |
| Remdesivir + Placebo | Change From Baseline in Neutrophils | Day 3 | 1.4128 10^9 cells/L | Standard Deviation 3.0236 |
| Remdesivir + Placebo | Change From Baseline in Neutrophils | Day 11 | 5.0504 10^9 cells/L | Standard Deviation 7.2784 |
| Remdesivir + Placebo | Change From Baseline in Neutrophils | Day 5 | 1.5750 10^9 cells/L | Standard Deviation 3.422 |
| Remdesivir + Placebo | Change From Baseline in Neutrophils | Day 29 | -1.2712 10^9 cells/L | Standard Deviation 4.209 |
| Remdesivir + Placebo | Change From Baseline in Neutrophils | Day 8 | 3.5547 10^9 cells/L | Standard Deviation 4.7093 |
Secondary
Change From Baseline in Platelets Count
Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Higher results are better, so a higher positive change from baseline indicates a more favorable outcome.
Time frame: Days 1, 3, 5, 8, 11, 15, 29
Population: The safety population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies with available data at baseline and post baseline assessment time point, analyzed as treated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Remdesivir + Lenzilumab | Change From Baseline in Platelets Count | Day 3 | 52.99 10^9 cells/L | Standard Deviation 59.89 |
| Remdesivir + Lenzilumab | Change From Baseline in Platelets Count | Day 5 | 84.38 10^9 cells/L | Standard Deviation 84.63 |
| Remdesivir + Lenzilumab | Change From Baseline in Platelets Count | Day 8 | 103.33 10^9 cells/L | Standard Deviation 127.75 |
| Remdesivir + Lenzilumab | Change From Baseline in Platelets Count | Day 11 | 54.43 10^9 cells/L | Standard Deviation 124.09 |
| Remdesivir + Lenzilumab | Change From Baseline in Platelets Count | Day 15 | 27.23 10^9 cells/L | Standard Deviation 123.15 |
| Remdesivir + Lenzilumab | Change From Baseline in Platelets Count | Day 29 | 15.11 10^9 cells/L | Standard Deviation 91.84 |
| Remdesivir + Placebo | Change From Baseline in Platelets Count | Day 15 | -3.72 10^9 cells/L | Standard Deviation 118.35 |
| Remdesivir + Placebo | Change From Baseline in Platelets Count | Day 3 | 47.61 10^9 cells/L | Standard Deviation 60.99 |
| Remdesivir + Placebo | Change From Baseline in Platelets Count | Day 11 | 31.99 10^9 cells/L | Standard Deviation 138.63 |
| Remdesivir + Placebo | Change From Baseline in Platelets Count | Day 5 | 72.92 10^9 cells/L | Standard Deviation 91.73 |
| Remdesivir + Placebo | Change From Baseline in Platelets Count | Day 29 | 59.53 10^9 cells/L | Standard Deviation 117.47 |
| Remdesivir + Placebo | Change From Baseline in Platelets Count | Day 8 | 83.09 10^9 cells/L | Standard Deviation 133.33 |
Secondary
Change From Baseline in Total Bilirubin
Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome.
Time frame: Days 1, 3, 5, 8, 11, 15, 29
Population: The safety population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies with available data at baseline and post baseline assessment time point, analyzed as treated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Remdesivir + Lenzilumab | Change From Baseline in Total Bilirubin | Day 3 | -0.049 mg/dL | Standard Deviation 0.21 |
| Remdesivir + Lenzilumab | Change From Baseline in Total Bilirubin | Day 5 | 0.064 mg/dL | Standard Deviation 0.318 |
| Remdesivir + Lenzilumab | Change From Baseline in Total Bilirubin | Day 8 | 0.082 mg/dL | Standard Deviation 0.348 |
| Remdesivir + Lenzilumab | Change From Baseline in Total Bilirubin | Day 11 | 0.096 mg/dL | Standard Deviation 0.366 |
| Remdesivir + Lenzilumab | Change From Baseline in Total Bilirubin | Day 15 | 0.078 mg/dL | Standard Deviation 0.494 |
| Remdesivir + Lenzilumab | Change From Baseline in Total Bilirubin | Day 29 | -0.043 mg/dL | Standard Deviation 0.268 |
| Remdesivir + Placebo | Change From Baseline in Total Bilirubin | Day 15 | 0.022 mg/dL | Standard Deviation 0.84 |
| Remdesivir + Placebo | Change From Baseline in Total Bilirubin | Day 3 | -0.039 mg/dL | Standard Deviation 0.508 |
| Remdesivir + Placebo | Change From Baseline in Total Bilirubin | Day 11 | 0.097 mg/dL | Standard Deviation 0.488 |
| Remdesivir + Placebo | Change From Baseline in Total Bilirubin | Day 5 | 0.007 mg/dL | Standard Deviation 0.592 |
| Remdesivir + Placebo | Change From Baseline in Total Bilirubin | Day 29 | -0.101 mg/dL | Standard Deviation 0.938 |
| Remdesivir + Placebo | Change From Baseline in Total Bilirubin | Day 8 | 0.068 mg/dL | Standard Deviation 0.318 |
Secondary
Change From Baseline in White Blood Cell (WBC) Count
Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Higher results are better, so a higher positive change from baseline indicates a more favorable outcome.
Time frame: Days 1, 3, 5, 8, 11, 15, 29
Population: The safety population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies with available data at baseline and post baseline assessment time point, analyzed as treated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Remdesivir + Lenzilumab | Change From Baseline in White Blood Cell (WBC) Count | Day 3 | 1.1678 10^9 cells/L | Standard Deviation 3.1129 |
| Remdesivir + Lenzilumab | Change From Baseline in White Blood Cell (WBC) Count | Day 5 | 3.1761 10^9 cells/L | Standard Deviation 4.6732 |
| Remdesivir + Lenzilumab | Change From Baseline in White Blood Cell (WBC) Count | Day 8 | 5.9017 10^9 cells/L | Standard Deviation 5.8181 |
| Remdesivir + Lenzilumab | Change From Baseline in White Blood Cell (WBC) Count | Day 11 | 6.9859 10^9 cells/L | Standard Deviation 6.5458 |
| Remdesivir + Lenzilumab | Change From Baseline in White Blood Cell (WBC) Count | Day 15 | 3.3979 10^9 cells/L | Standard Deviation 6.2653 |
| Remdesivir + Lenzilumab | Change From Baseline in White Blood Cell (WBC) Count | Day 29 | -0.3185 10^9 cells/L | Standard Deviation 5.2892 |
| Remdesivir + Placebo | Change From Baseline in White Blood Cell (WBC) Count | Day 15 | 2.2880 10^9 cells/L | Standard Deviation 6.3102 |
| Remdesivir + Placebo | Change From Baseline in White Blood Cell (WBC) Count | Day 3 | 1.7775 10^9 cells/L | Standard Deviation 3.1355 |
| Remdesivir + Placebo | Change From Baseline in White Blood Cell (WBC) Count | Day 11 | 6.0658 10^9 cells/L | Standard Deviation 7.6772 |
| Remdesivir + Placebo | Change From Baseline in White Blood Cell (WBC) Count | Day 5 | 2.4411 10^9 cells/L | Standard Deviation 4.0829 |
| Remdesivir + Placebo | Change From Baseline in White Blood Cell (WBC) Count | Day 29 | -0.1199 10^9 cells/L | Standard Deviation 5.5121 |
| Remdesivir + Placebo | Change From Baseline in White Blood Cell (WBC) Count | Day 8 | 4.6654 10^9 cells/L | Standard Deviation 4.8122 |
Secondary
Days of Invasive Mechanical Ventilation/Extracorporeal Membrane Oxygenation (ECMO) Use
Duration of invasive ventilation/ECMO was measured in days among participants who required invasive ventilation or died.
Time frame: Day 1 through Day 29
Population: The intention-to-treat (ITT) population includes all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remdesivir + Lenzilumab | Days of Invasive Mechanical Ventilation/Extracorporeal Membrane Oxygenation (ECMO) Use | 0.0 days |
| Remdesivir + Placebo | Days of Invasive Mechanical Ventilation/Extracorporeal Membrane Oxygenation (ECMO) Use | 0.0 days |
Secondary
Days of New Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) Use
Duration of new invasive mechanical ventilation/ECMO use was measured in days among participants not on invasive ventilation/ECMO at baseline who progressed to invasive ventilation/ECMO or died.
Time frame: Day 1 through Day 29
Population: The intention-to-treat (ITT) population includes all randomized participants. Only participants not on invasive ventilation/ECMO at baseline were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remdesivir + Lenzilumab | Days of New Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) Use | 0.0 days |
| Remdesivir + Placebo | Days of New Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) Use | 0.0 days |
Secondary
Days of New Non-invasive Ventilation/High Flow Oxygen Use
Duration of new non-invasive ventilation or high flow oxygen use was measured in days among participants not on non-invasive ventilation/high flow oxygen at baseline who progressed to non-invasive ventilation/high flow oxygen, invasive ventilation/ECMO or died.
Time frame: Day 1 through Day 29
Population: The intention-to-treat (mITT) population includes all randomized participants. Only participants in the 'hospitalized requiring new or increased supplemental oxygen ordinal scale' or better at baseline were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remdesivir + Lenzilumab | Days of New Non-invasive Ventilation/High Flow Oxygen Use | 0.0 days |
| Remdesivir + Placebo | Days of New Non-invasive Ventilation/High Flow Oxygen Use | 0.0 days |
Secondary
Days of Non-invasive Ventilation/High Flow Oxygen Use
Duration of non-invasive ventilation or high flow oxygen use was measured in days among participants who required non-invasive ventilation/high flow oxygen, invasive ventilation/ECMO or died.
Time frame: Day 1 through Day 29
Population: The intention-to-treat (ITT) population includes all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remdesivir + Lenzilumab | Days of Non-invasive Ventilation/High Flow Oxygen Use | 1.0 days |
| Remdesivir + Placebo | Days of Non-invasive Ventilation/High Flow Oxygen Use | 2.0 days |
Secondary
Days of Supplemental Oxygen Use
Duration of supplemental oxygen use was measured in days among participants who required any supplemental oxygen, non-invasive ventilation/high flow oxygen, invasive ventilation/ECMO or died.
Time frame: Day 1 through Day 29
Population: The intention-to-treat (mITT) population includes all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remdesivir + Lenzilumab | Days of Supplemental Oxygen Use | 13.5 days |
| Remdesivir + Placebo | Days of Supplemental Oxygen Use | 14.0 days |
Secondary
Duration of Hospitalization
Duration of hospitalization is defined first as the total number of days hospitalized for COVID-19, including readmissions for COVID-19-related reasons. It is also calculated as the total number of days hospitalized, including any readmissions for any reason.
Time frame: Day 1 through Day 29
Population: The intention-to-treat (ITT) population includes all randomized participants.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Remdesivir + Lenzilumab | Duration of Hospitalization | Hospitalized for COVID-19 | 8.0 days |
| Remdesivir + Lenzilumab | Duration of Hospitalization | Hospitalized for Any Reason | 8.0 days |
| Remdesivir + Placebo | Duration of Hospitalization | Hospitalized for COVID-19 | 8.0 days |
| Remdesivir + Placebo | Duration of Hospitalization | Hospitalized for Any Reason | 8.0 days |
Secondary
Mean Change in Ordinal Scale
The ordinal scale categories are defined as: 1) Not hospitalized, no new or increased limitations on activities;2) Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home oxygen, CPAP, or BiPAP; 3) Hospitalized, not requiring new or increased supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring new or increased supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring new or increased supplemental oxygen; 6) Hospitalized, requiring new or increased non-invasive ventilation or highflow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death. A positive change indicates a worsening and a negative change is an improvement.
Time frame: Days 1, 3, 5, 8, 11, 15, 22, 29
Population: The intention-to-treat (ITT) population includes all randomized participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Remdesivir + Lenzilumab | Mean Change in Ordinal Scale | Day 3 | 0.0 units on a scale | Standard Deviation 0.6 |
| Remdesivir + Lenzilumab | Mean Change in Ordinal Scale | Day 5 | -0.3 units on a scale | Standard Deviation 1.1 |
| Remdesivir + Lenzilumab | Mean Change in Ordinal Scale | Day 22 | -2.6 units on a scale | Standard Deviation 2.1 |
| Remdesivir + Lenzilumab | Mean Change in Ordinal Scale | Day 8 | -1.3 units on a scale | Standard Deviation 1.9 |
| Remdesivir + Lenzilumab | Mean Change in Ordinal Scale | Day 11 | -1.8 units on a scale | Standard Deviation 2 |
| Remdesivir + Lenzilumab | Mean Change in Ordinal Scale | Day 15 | -2.3 units on a scale | Standard Deviation 2.2 |
| Remdesivir + Lenzilumab | Mean Change in Ordinal Scale | Day 29 | -2.8 units on a scale | Standard Deviation 2.2 |
| Remdesivir + Placebo | Mean Change in Ordinal Scale | Day 22 | -2.4 units on a scale | Standard Deviation 2.3 |
| Remdesivir + Placebo | Mean Change in Ordinal Scale | Day 11 | -1.8 units on a scale | Standard Deviation 2 |
| Remdesivir + Placebo | Mean Change in Ordinal Scale | Day 3 | 0.1 units on a scale | Standard Deviation 0.4 |
| Remdesivir + Placebo | Mean Change in Ordinal Scale | Day 29 | -2.6 units on a scale | Standard Deviation 2.3 |
| Remdesivir + Placebo | Mean Change in Ordinal Scale | Day 5 | -0.2 units on a scale | Standard Deviation 1.1 |
| Remdesivir + Placebo | Mean Change in Ordinal Scale | Day 15 | -2.2 units on a scale | Standard Deviation 2.2 |
| Remdesivir + Placebo | Mean Change in Ordinal Scale | Day 8 | -1.3 units on a scale | Standard Deviation 2 |
Secondary
Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8
The ordinal scale categories are defined as: 1) Not hospitalized, no new or increased limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home oxygen, CPAP, or BiPAP; 3) Hospitalized, not requiring new or increased supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring new or increased supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring new or increased supplemental oxygen; 6) Hospitalized, requiring new or increased non-invasive ventilation or highflow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death
Time frame: Day 8
Population: The intention-to-treat (ITT) population includes all randomized participants.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Remdesivir + Lenzilumab | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | 7. Hospitalized, on invasive mechanical ventilation or ECMO | 31 Participants |
| Remdesivir + Lenzilumab | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | 3. Hospitalized, not req new or increased supplemental O2 - no longer req ongoing medical care | 3 Participants |
| Remdesivir + Lenzilumab | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | 1. Not hospitalized, no new or increased limitations on activities | 36 Participants |
| Remdesivir + Lenzilumab | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | 4. Hospitalized, not req new or increased supplemental O2 - req ongoing medical care | 8 Participants |
| Remdesivir + Lenzilumab | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | 8. Death | 6 Participants |
| Remdesivir + Lenzilumab | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | 5. Hospitalized, requiring new or increased supplemental O2 | 65 Participants |
| Remdesivir + Lenzilumab | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | 2. Not. hosp., but new or incr. limit on activities and/or req. new or incr. home O2, CPAP, or BiPAP | 71 Participants |
| Remdesivir + Lenzilumab | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | 6. Hospitalized, requiring new or increased non-invasive ventilation or high-flow oxygen devices | 52 Participants |
| Remdesivir + Placebo | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | 2. Not. hosp., but new or incr. limit on activities and/or req. new or incr. home O2, CPAP, or BiPAP | 69 Participants |
| Remdesivir + Placebo | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | 7. Hospitalized, on invasive mechanical ventilation or ECMO | 26 Participants |
| Remdesivir + Placebo | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | 8. Death | 6 Participants |
| Remdesivir + Placebo | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | 1. Not hospitalized, no new or increased limitations on activities | 38 Participants |
| Remdesivir + Placebo | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | 6. Hospitalized, requiring new or increased non-invasive ventilation or high-flow oxygen devices | 58 Participants |
| Remdesivir + Placebo | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | 3. Hospitalized, not req new or increased supplemental O2 - no longer req ongoing medical care | 0 Participants |
| Remdesivir + Placebo | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | 4. Hospitalized, not req new or increased supplemental O2 - req ongoing medical care | 8 Participants |
| Remdesivir + Placebo | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | 5. Hospitalized, requiring new or increased supplemental O2 | 50 Participants |
Comparison: Includes all ordinal score categories. Odds ratio of a better clinical status score, confidence interval and p-value estimated from a proportional odds model adjusted for baseline steroid use and baseline ordinal score. Missing data imputed using multiple imputation (MI) for participants lost to follow-up before Day 8 while hospitalized, in hospice, long term acute care, or transferred to other hospital while those participants lost to follow-up after discharge to home are assigned a score of 2.p-value: 0.90795% CI: [0.75, 1.39]Proportional odds model
Secondary
Number of Participants Reporting Grade 3, 4, or 5 Clinical and/or Laboratory Adverse Events (AEs)
Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening while Grade 5 AEs are those that are fatal. Laboratory results were considered AEs if they were grade 3 or above according to the thresholds in the Division of AIDS (DAIDS) Table for Grading the Severity of Adverse Events.
Time frame: Day 1 through Day 60
Population: The safety population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies, analyzed as treated.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Remdesivir + Lenzilumab | Number of Participants Reporting Grade 3, 4, or 5 Clinical and/or Laboratory Adverse Events (AEs) | 133 Participants |
| Remdesivir + Placebo | Number of Participants Reporting Grade 3, 4, or 5 Clinical and/or Laboratory Adverse Events (AEs) | 124 Participants |
Secondary
Number of Participants Reporting Serious Adverse Events (SAEs)
An SAE is defined as an AE or suspected adverse reaction that is considered serious if, in the view of either the investigator or the sponsor, it results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.
Time frame: Day 1 through Day 60
Population: The safety population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies, analyzed as treated.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Remdesivir + Lenzilumab | Number of Participants Reporting Serious Adverse Events (SAEs) | 76 Participants |
| Remdesivir + Placebo | Number of Participants Reporting Serious Adverse Events (SAEs) | 81 Participants |
Secondary
Number of Participants Who Discontinued or Temporarily Suspended Study Treatment
Discontinuation or temporary suspension of study product is defined as any episode of early discontinuation or interruption of study product administration.
Time frame: Day 1 through Day 29
Population: The safety population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies, analyzed as treated.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Remdesivir + Lenzilumab | Number of Participants Who Discontinued or Temporarily Suspended Study Treatment | 6 Participants |
| Remdesivir + Placebo | Number of Participants Who Discontinued or Temporarily Suspended Study Treatment | 20 Participants |
Secondary
Number of Participants With New Invasive Mechanical Ventilation / Extracorporeal Membrane Oxygenation (ECMO) Use
New Invasive Mechanical Ventilation / Extracorporeal Membrane Oxygenation (ECMO) Use is defined as participants not on invasive ventilation/ECMO at baseline who progressed to invasive ventilation/ECMO or died during the study.
Time frame: Day 1 through Day 29
Population: The intention-to-treat (ITT) population includes all randomized participants. Only participants not on invasive ventilation/ECMO at baseline were included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Remdesivir + Lenzilumab | Number of Participants With New Invasive Mechanical Ventilation / Extracorporeal Membrane Oxygenation (ECMO) Use | 44 Participants |
| Remdesivir + Placebo | Number of Participants With New Invasive Mechanical Ventilation / Extracorporeal Membrane Oxygenation (ECMO) Use | 47 Participants |
Secondary
Number of Participants With New Non-invasive Ventilation/High Flow Oxygen Use
New Non-invasive Ventilation/High Flow Oxygen Use is defined as participants in the hospitalized requiring new or increased supplemental oxygen ordinal scale or below at baseline who progressed to noninvasive ventilation/high flow oxygen, invasive ventilation/ECMO or died during the study.
Time frame: Day 1 through Day 29
Population: The intention-to-treat (ITT) population includes all randomized participants. Only participants in the 'hospitalized requiring new or increased supplemental oxygen ordinal scale' or better at baseline were included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Remdesivir + Lenzilumab | Number of Participants With New Non-invasive Ventilation/High Flow Oxygen Use | 49 Participants |
| Remdesivir + Placebo | Number of Participants With New Non-invasive Ventilation/High Flow Oxygen Use | 62 Participants |
Secondary
Proportion of Participants Alive and Without Mechanical Ventilation Through Day 29 in Participants With Any Baseline Ordinal Score
Mechanical ventilation-free survival was assessed through Day 29, defined as the proportion of participants who had not died nor were hospitalized on invasive mechanical ventilation or ECMO from Day 1 through Day 29. Estimates for the proportions are estimated from a logistic regression model adjusted for baseline dexamethasone, baseline ordinal score, age (continuous), and baseline CRP.
Time frame: Day 1 through Day 29
Population: The intention-to-treat (ITT) population includes all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Remdesivir + Lenzilumab | Proportion of Participants Alive and Without Mechanical Ventilation Through Day 29 in Participants With Any Baseline Ordinal Score | 0.83 Proportion of participants |
| Remdesivir + Placebo | Proportion of Participants Alive and Without Mechanical Ventilation Through Day 29 in Participants With Any Baseline Ordinal Score | 0.80 Proportion of participants |
Comparison: Odds ratio, CI, and p-value estimated from a logistic regression model adjusted for baseline dexamethasone use, baseline OS, age (continuous), and baseline CRP. Missing data imputed using the 3-stage multiple imputation procedure described in the statistical analysis plan.p-value: 0.37895% CI: [0.77, 1.99]Regression, Logistic
Secondary
Proportion of Participants Not Meeting Criteria for One of Two Ordinal Scale Categories at Day 29
Ordinal scale categories include 7) Hospitalized, on Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) and 8) Death. Defined as the proportion of participants who were alive and were not hospitalized on invasive mechanical ventilation or ECMO at the Day 29 visit.
Time frame: Day 29
Population: The intention-to-treat (ITT) population includes all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Remdesivir + Lenzilumab | Proportion of Participants Not Meeting Criteria for One of Two Ordinal Scale Categories at Day 29 | 0.86 Proportion of participants |
| Remdesivir + Placebo | Proportion of Participants Not Meeting Criteria for One of Two Ordinal Scale Categories at Day 29 | 0.83 Proportion of participants |
Secondary
Time to an Improvement of One Category From Baseline Using an Ordinal Scale
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Not hospitalized, no new or increased limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home oxygen, CPAP, or BiPAP; 3) Hospitalized, not requiring new or increased supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring new or increased supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring new or increased supplemental oxygen; 6) Hospitalized, requiring new or increased noninvasive ventilation or high-flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.
Time frame: Day 1 through Day 60
Population: The intention-to-treat (ITT) population includes all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remdesivir + Lenzilumab | Time to an Improvement of One Category From Baseline Using an Ordinal Scale | 8.0 days |
| Remdesivir + Placebo | Time to an Improvement of One Category From Baseline Using an Ordinal Scale | 7.0 days |
p-value: 0.60995% CI: [0.87, 1.27]Regression, Cox
Secondary
Time to an Improvement of Two Categories From Baseline Using an Ordinal Scale
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Not hospitalized, no new or increased limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home oxygen, CPAP, or BiPAP; 3) Hospitalized, not requiring new or increased supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring new or increased supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring new or increased supplemental oxygen; 6) Hospitalized, requiring new or increased noninvasive ventilation or high-flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.
Time frame: Day 1 through Day 60
Population: The intention-to-treat (ITT) population includes all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remdesivir + Lenzilumab | Time to an Improvement of Two Categories From Baseline Using an Ordinal Scale | 13.0 days |
| Remdesivir + Placebo | Time to an Improvement of Two Categories From Baseline Using an Ordinal Scale | 13.0 days |
p-value: 0.70895% CI: [0.85, 1.26]Regression, Cox
Secondary
Time to Death
The time to death from study Day 1 to study Day 29, measured in days. The times reported are Kaplan-Meier estimates.
Time frame: Day 1 through Day 29
Population: The safety population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies, classified by their actual treatment assignment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remdesivir + Lenzilumab | Time to Death | NA days |
| Remdesivir + Placebo | Time to Death | NA days |
Secondary
Time to Sustained Recovery in Participants With a Baseline Ordinal Score of 5 or 6, CRP<150mg/L and Age <85 Years
Day of sustained recovery is defined as the first day on which the participant satisfies 1 of the following 3 categories from the clinical status ordinal scale (and does not return to a score of = 4 up to and including Study Day 60): 1) Not hospitalized, no new or increased limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home oxygen, Continuous Positive Airway Pressure (CPAP), or Bilevel Positive Airway Pressure (BiPAP); 3) Hospitalized, not requiring new or increased supplemental oxygen - no longer requires ongoing medical care.
Time frame: Day 1 through Day 60
Population: The primary subgroup population includes all randomized participants with a baseline ordinal score of 5 or 6, CRP\<150 mg/L at baseline, and age\<85 years.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remdesivir + Lenzilumab | Time to Sustained Recovery in Participants With a Baseline Ordinal Score of 5 or 6, CRP<150mg/L and Age <85 Years | 8.0 days |
| Remdesivir + Placebo | Time to Sustained Recovery in Participants With a Baseline Ordinal Score of 5 or 6, CRP<150mg/L and Age <85 Years | 7.0 days |
p-value: 0.68995% CI: [0.76, 1.2]Regression, Cox
Secondary
Time to Sustained Recovery in Participants With Any Baseline Ordinal Score
Day of sustained recovery is defined as the first day on which the participant satisfies 1 of the following 3 categories from the clinical status ordinal scale (and does not return to a score of = 4 up to and including Study Day 60): 1) Not hospitalized, no new or increased limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home oxygen, CPAP, or BiPAP; 3) Hospitalized, not requiring new or increased supplemental oxygen - no longer requires ongoing medical care.
Time frame: Day 1 through Day 60
Population: The intention-to-treat (ITT) population includes all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remdesivir + Lenzilumab | Time to Sustained Recovery in Participants With Any Baseline Ordinal Score | 8.0 days |
| Remdesivir + Placebo | Time to Sustained Recovery in Participants With Any Baseline Ordinal Score | 8.0 days |
Comparison: Hazard ratio, confidence intervals, and p-value estimated from a Cox model adjusted for baseline dexamethasone use, baseline ordinal Score, age, and baseline CRP.p-value: 0.71895% CI: [0.79, 1.18]Regression, Cox