COVID-19
Conditions
Keywords
Adults, COVID-19, Multicenter, Platform, 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-A stage will evaluate the combination of remdesivir with risankizumab vs remdesivir with a risankizumab 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-A stage will evaluate the combination of remdesivir with risankizumab vs remdesivir with a risankizumab 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 1) to 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
OTHERPlacebo
Risankizumab placebo will be given at an equal volume at the same schedule.
DRUGRemdesivir
Remdesivir is a single diastereomer monophosphoramidate prodrug for the intracellular delivery of a modified adenine nucleoside analog GS-441524.
BIOLOGICALRisankizumab
Risankizumab is a humanized immunoglobulin (Ig) G1 antagonistic monoclonal antibody (mAb) directed against the p19 subunit of the human cytokine interleukin-23. Risankizumab is formulated in a buffer of 4.4 mM disodium succinate hexahydrate/succinic acid, 225 mM sorbitol, 0.2 mg/mL polysorbate 20, and WFI in a 6R vial.
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 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 IP dosing. Note: 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 an 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 an 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 two or more doses of \> 60 mg of prednisone or equivalent in the 7 days prior to screening. 8. 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. 9. 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. 10. 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. 11. Received Granulocyte-macrophage colony-stimulating factor (GM-CSF) agents (e.g., sargramostim) within 2 months prior to screening. 12. Received other immunosuppressants in the 4 weeks prior to screening and in the judgment of the investigator, the risk of immunosuppression with risankizumab is larger than the risk of Coronavirus Disease 2019 (COVID-19). 13. Received any live vaccine in the 4 weeks prior to screening. 14. Known active tuberculosis. 15. Known history of Human Immunodeficiency Virus (HIV), Hepatitis B (HBV) or untreated hepatitis C (HCV) infection. 16. History of pulmonary alveolar proteinosis (PAP). 17. Has a malignancy and currently receiving immunosuppressive chemotherapy, immunodeficiency, uncontrolled opportunistic infection, or uncontrolled cirrhosis. 18. Has a medical condition that could, in the judgment of the investigator, limit the interpretation and generalizability of trial results. 19. Positive test for influenza virus during the current illness (influenza testing is not required by protocol). 20. Previous participation in an ACTIV-5/Big Effect Trial (BET)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 high-flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Sustained Recovery | 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 15 | Day 15 | 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 high-flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death. |
| Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29 | Day 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 high-flow 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| Change From Baseline in Aspartate Transaminase (AST) | 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. |
| 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. |
| 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. |
| 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. |
| Change From Baseline in Platelets | 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. |
| Change From Baseline in 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. |
| Change From Baseline in White Blood Cell (WBC) | 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| Number of Participants Reporting Grade 3 and 4 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. |
| 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 New Invasive Mechanical Ventilation / 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. |
| 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 non-invasive ventilation/high flow oxygen, invasive ventilation/ECMO or died during the study. |
| Mean Change in Ordinal Scale | Day 1, 3, 5, 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 high-flow 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. |
| Proportion of Participants Not Meeting Criteria for One of Two Ordinal Scale Categories at Day 29 | Day 29 | Ordinal scale categories include 8) Death and 7) Hospitalized, on Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO). Defined as the proportion of participants who were alive and were not hospitalized on invasive mechanical ventilation or ECMO at the Day 29 visit. |
| 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. |
| 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. |
| Proportion of Participants Not Meeting Criteria for One of Two Ordinal Scale Categories Through Day 29 | Day 1 through Day 29 | Ordinal scale categories include 8) Death and 7) Hospitalized, on Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO). 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. Results are reported as Kaplan Meier estimates. |
| 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 non-invasive 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 non-invasive 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 death from study Day 1 to study Day 29, measured in days. The times reported are Kaplan-Meier estimates. |
| 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 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. |
Countries
United States
Participant flow
Recruitment details
Participants were male and non-pregnant female adults =18 years of age or older and hospitalized with COVID-19. Participants were enrolled between 23OCT2020 and 13JUL2021.
Participants by arm
| Arm | Count |
|---|---|
| Remdesivir + Risankizumab 200-mg 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 1200-mg IV risankizumab infusion (300-mg x 4 vials) once on Day 1. | 104 |
| Remdesivir + Placebo 200-mg 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 1200-mg IV risankizumab placebo infusion (300-mg x 4 vials) once on Day 1. | 110 |
| Total | 214 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 9 | 11 |
| Overall Study | Lost to Follow-up | 7 | 9 |
| Overall Study | Protocol Violation | 2 | 0 |
| Overall Study | Randomized but not dosed | 2 | 3 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
| Overall Study | Withdrawal of consent before product administration | 1 | 0 |
Baseline characteristics
| Characteristic | Remdesivir + Risankizumab | Remdesivir + Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 18 Participants | 32 Participants | 50 Participants |
| Age, Categorical Between 18 and 65 years | 86 Participants | 78 Participants | 164 Participants |
| Age, Continuous | 54.5 years STANDARD_DEVIATION 12.2 | 57.5 years STANDARD_DEVIATION 13.1 | 56.0 years STANDARD_DEVIATION 12.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 23 Participants | 20 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 81 Participants | 89 Participants | 170 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 6 Participants | 14 Participants |
| Race (NIH/OMB) Black or African American | 25 Participants | 28 Participants | 53 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 12 Participants | 8 Participants | 20 Participants |
| Race (NIH/OMB) White | 59 Participants | 67 Participants | 126 Participants |
| Region of Enrollment United States | 104 participants | 110 participants | 214 participants |
| Sex: Female, Male Female | 36 Participants | 52 Participants | 88 Participants |
| Sex: Female, Male Male | 68 Participants | 58 Participants | 126 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 9 / 104 | 11 / 110 |
| other Total, other adverse events | 24 / 100 | 22 / 107 |
| serious Total, serious adverse events | 24 / 100 | 26 / 107 |
Outcome results
Primary
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 high-flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.
Time frame: Day 8
Population: The modified intention-to-treat (mITT) population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies, analyzed as randomized.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Remdesivir + Risankizumab | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | Not hosp., but new or incr. limit on activities and/or req. new or incr. home O2, CPAP, or BiPAP | 36 Participants |
| Remdesivir + Risankizumab | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | Hospitalized, requiring new or increased non-invasive ventilation or high-flow oxygen devices | 13 Participants |
| Remdesivir + Risankizumab | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | Hospitalized, not req new or increased supplemental O2 - req ongoing medical care | 6 Participants |
| Remdesivir + Risankizumab | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | Hospitalized, on invasive mechanical ventilation or ECMO | 11 Participants |
| Remdesivir + Risankizumab | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | Hospitalized, not req new or increased supplemental O2 - no longer req ongoing medical care | 0 Participants |
| Remdesivir + Risankizumab | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | Death | 2 Participants |
| Remdesivir + Risankizumab | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | Hospitalized, requiring new or increased supplemental O2 | 17 Participants |
| Remdesivir + Risankizumab | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | Missing | 0 Participants |
| Remdesivir + Risankizumab | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | Not hospitalized, no new or increased limitations on activities | 15 Participants |
| Remdesivir + Placebo | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | Missing | 1 Participants |
| Remdesivir + Placebo | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | Not hospitalized, no new or increased limitations on activities | 21 Participants |
| Remdesivir + Placebo | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | Not hosp., but new or incr. limit on activities and/or req. new or incr. home O2, CPAP, or BiPAP | 36 Participants |
| Remdesivir + Placebo | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | 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 | Hospitalized, not req new or increased supplemental O2 - req ongoing medical care | 3 Participants |
| Remdesivir + Placebo | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | Hospitalized, requiring new or increased supplemental O2 | 16 Participants |
| Remdesivir + Placebo | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | Hospitalized, requiring new or increased non-invasive ventilation or high-flow oxygen devices | 19 Participants |
| Remdesivir + Placebo | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | Hospitalized, on invasive mechanical ventilation or ECMO | 9 Participants |
| Remdesivir + Placebo | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 | Death | 2 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 participants lost to follow-up after discharge to home are assigned a score of 2.p-value: 0.92795% CI: [0.59, 1.61]Proportional odds model
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 + Risankizumab | 14-day Participant Mortality | 0.06 Proportion of participants |
| Remdesivir + Placebo | 14-day Participant Mortality | 0.03 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 + Risankizumab | 28-day Participant Mortality | 0.07 Proportion of participants |
| Remdesivir + Placebo | 28-day Participant Mortality | 0.08 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 + Risankizumab | 59-day Participant Mortality | 0.09 Proportion of participants |
| Remdesivir + Placebo | 59-day Participant Mortality | 0.11 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.
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 + Risankizumab | Change From Baseline in Alanine Aminotransferase (ALT) | Day 3 | 6.1 U/L | Standard Deviation 25.8 |
| Remdesivir + Risankizumab | Change From Baseline in Alanine Aminotransferase (ALT) | Day 5 | 9.4 U/L | Standard Deviation 34.7 |
| Remdesivir + Risankizumab | Change From Baseline in Alanine Aminotransferase (ALT) | Day 8 | 6.1 U/L | Standard Deviation 48.3 |
| Remdesivir + Risankizumab | Change From Baseline in Alanine Aminotransferase (ALT) | Day 11 | 5.3 U/L | Standard Deviation 55.7 |
| Remdesivir + Risankizumab | Change From Baseline in Alanine Aminotransferase (ALT) | Day 15 | 7.6 U/L | Standard Deviation 45.9 |
| Remdesivir + Risankizumab | Change From Baseline in Alanine Aminotransferase (ALT) | Day 29 | -0.1 U/L | Standard Deviation 31.6 |
| Remdesivir + Placebo | Change From Baseline in Alanine Aminotransferase (ALT) | Day 15 | -3.3 U/L | Standard Deviation 55.3 |
| Remdesivir + Placebo | Change From Baseline in Alanine Aminotransferase (ALT) | Day 3 | 9.6 U/L | Standard Deviation 43.5 |
| Remdesivir + Placebo | Change From Baseline in Alanine Aminotransferase (ALT) | Day 11 | 21.5 U/L | Standard Deviation 117.7 |
| Remdesivir + Placebo | Change From Baseline in Alanine Aminotransferase (ALT) | Day 5 | 64.0 U/L | Standard Deviation 290.4 |
| Remdesivir + Placebo | Change From Baseline in Alanine Aminotransferase (ALT) | Day 29 | -19.3 U/L | Standard Deviation 62.1 |
| Remdesivir + Placebo | Change From Baseline in Alanine Aminotransferase (ALT) | Day 8 | 33.9 U/L | Standard Deviation 168.1 |
Secondary
Change From Baseline in Aspartate Transaminase (AST)
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.
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 + Risankizumab | Change From Baseline in Aspartate Transaminase (AST) | Day 3 | -1.4 U/L | Standard Deviation 39.9 |
| Remdesivir + Risankizumab | Change From Baseline in Aspartate Transaminase (AST) | Day 5 | -8.4 U/L | Standard Deviation 36.6 |
| Remdesivir + Risankizumab | Change From Baseline in Aspartate Transaminase (AST) | Day 8 | -16.7 U/L | Standard Deviation 37.6 |
| Remdesivir + Risankizumab | Change From Baseline in Aspartate Transaminase (AST) | Day 11 | -8.9 U/L | Standard Deviation 45.1 |
| Remdesivir + Risankizumab | Change From Baseline in Aspartate Transaminase (AST) | Day 15 | -13.8 U/L | Standard Deviation 34.6 |
| Remdesivir + Risankizumab | Change From Baseline in Aspartate Transaminase (AST) | Day 29 | -13.1 U/L | Standard Deviation 22.4 |
| Remdesivir + Placebo | Change From Baseline in Aspartate Transaminase (AST) | Day 15 | -16.9 U/L | Standard Deviation 33 |
| Remdesivir + Placebo | Change From Baseline in Aspartate Transaminase (AST) | Day 3 | -5.0 U/L | Standard Deviation 46.4 |
| Remdesivir + Placebo | Change From Baseline in Aspartate Transaminase (AST) | Day 11 | 39.4 U/L | Standard Deviation 318 |
| Remdesivir + Placebo | Change From Baseline in Aspartate Transaminase (AST) | Day 5 | 44.2 U/L | Standard Deviation 432.3 |
| Remdesivir + Placebo | Change From Baseline in Aspartate Transaminase (AST) | Day 29 | -28.2 U/L | Standard Deviation 37.3 |
| Remdesivir + Placebo | Change From Baseline in Aspartate Transaminase (AST) | Day 8 | 34.9 U/L | Standard Deviation 404 |
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.
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 + Risankizumab | Change From Baseline in Basophils | Day 3 | 0.0101 10^9 cells/L | Standard Deviation 0.0561 |
| Remdesivir + Risankizumab | Change From Baseline in Basophils | Day 5 | 0.0038 10^9 cells/L | Standard Deviation 0.0315 |
| Remdesivir + Risankizumab | Change From Baseline in Basophils | Day 8 | 0.0455 10^9 cells/L | Standard Deviation 0.2018 |
| Remdesivir + Risankizumab | Change From Baseline in Basophils | Day 11 | 0.0291 10^9 cells/L | Standard Deviation 0.0288 |
| Remdesivir + Risankizumab | Change From Baseline in Basophils | Day 15 | 0.0202 10^9 cells/L | Standard Deviation 0.0348 |
| Remdesivir + Risankizumab | Change From Baseline in Basophils | Day 29 | 0.0262 10^9 cells/L | Standard Deviation 0.0343 |
| Remdesivir + Placebo | Change From Baseline in Basophils | Day 15 | 0.0254 10^9 cells/L | Standard Deviation 0.0307 |
| Remdesivir + Placebo | Change From Baseline in Basophils | Day 3 | 0.0052 10^9 cells/L | Standard Deviation 0.0286 |
| Remdesivir + Placebo | Change From Baseline in Basophils | Day 11 | 0.0123 10^9 cells/L | Standard Deviation 0.0357 |
| Remdesivir + Placebo | Change From Baseline in Basophils | Day 5 | 0.0039 10^9 cells/L | Standard Deviation 0.0275 |
| Remdesivir + Placebo | Change From Baseline in Basophils | Day 29 | 0.0425 10^9 cells/L | Standard Deviation 0.0387 |
| Remdesivir + Placebo | Change From Baseline in Basophils | Day 8 | 0.0061 10^9 cells/L | Standard Deviation 0.0308 |
Secondary
Change From Baseline in 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.
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 + Risankizumab | Change From Baseline in Bilirubin | Day 3 | -0.033 mg/dL | Standard Deviation 0.201 |
| Remdesivir + Risankizumab | Change From Baseline in Bilirubin | Day 5 | -0.020 mg/dL | Standard Deviation 0.267 |
| Remdesivir + Risankizumab | Change From Baseline in Bilirubin | Day 8 | 0.016 mg/dL | Standard Deviation 0.336 |
| Remdesivir + Risankizumab | Change From Baseline in Bilirubin | Day 11 | 0.153 mg/dL | Standard Deviation 0.467 |
| Remdesivir + Risankizumab | Change From Baseline in Bilirubin | Day 15 | 0.157 mg/dL | Standard Deviation 0.494 |
| Remdesivir + Risankizumab | Change From Baseline in Bilirubin | Day 29 | -0.033 mg/dL | Standard Deviation 0.291 |
| Remdesivir + Placebo | Change From Baseline in Bilirubin | Day 15 | 0.131 mg/dL | Standard Deviation 0.43 |
| Remdesivir + Placebo | Change From Baseline in Bilirubin | Day 3 | -0.024 mg/dL | Standard Deviation 0.152 |
| Remdesivir + Placebo | Change From Baseline in Bilirubin | Day 11 | 0.148 mg/dL | Standard Deviation 0.581 |
| Remdesivir + Placebo | Change From Baseline in Bilirubin | Day 5 | 0.026 mg/dL | Standard Deviation 0.249 |
| Remdesivir + Placebo | Change From Baseline in Bilirubin | Day 29 | -0.091 mg/dL | Standard Deviation 0.223 |
| Remdesivir + Placebo | Change From Baseline in Bilirubin | Day 8 | 0.076 mg/dL | Standard Deviation 0.343 |
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.
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 + Risankizumab | Change From Baseline in C-Reactive Protein (CRP) | Day 3 | -49.471 milligrams/liter (mg/L) | Standard Deviation 68.217 |
| Remdesivir + Risankizumab | Change From Baseline in C-Reactive Protein (CRP) | Day 5 | -64.340 milligrams/liter (mg/L) | Standard Deviation 77.43 |
| Remdesivir + Risankizumab | Change From Baseline in C-Reactive Protein (CRP) | Day 8 | -62.578 milligrams/liter (mg/L) | Standard Deviation 82.042 |
| Remdesivir + Risankizumab | Change From Baseline in C-Reactive Protein (CRP) | Day 11 | -17.365 milligrams/liter (mg/L) | Standard Deviation 138.044 |
| Remdesivir + Risankizumab | Change From Baseline in C-Reactive Protein (CRP) | Day 15 | -66.453 milligrams/liter (mg/L) | Standard Deviation 76.258 |
| Remdesivir + Risankizumab | Change From Baseline in C-Reactive Protein (CRP) | Day 29 | -77.527 milligrams/liter (mg/L) | Standard Deviation 69.087 |
| Remdesivir + Placebo | Change From Baseline in C-Reactive Protein (CRP) | Day 15 | -58.816 milligrams/liter (mg/L) | Standard Deviation 70.797 |
| Remdesivir + Placebo | Change From Baseline in C-Reactive Protein (CRP) | Day 3 | -37.344 milligrams/liter (mg/L) | Standard Deviation 64.622 |
| Remdesivir + Placebo | Change From Baseline in C-Reactive Protein (CRP) | Day 11 | -49.828 milligrams/liter (mg/L) | Standard Deviation 143.271 |
| Remdesivir + Placebo | Change From Baseline in C-Reactive Protein (CRP) | Day 5 | -51.216 milligrams/liter (mg/L) | Standard Deviation 80.23 |
| Remdesivir + Placebo | Change From Baseline in C-Reactive Protein (CRP) | Day 29 | -68.496 milligrams/liter (mg/L) | Standard Deviation 74.662 |
| Remdesivir + Placebo | Change From Baseline in C-Reactive Protein (CRP) | Day 8 | -58.094 milligrams/liter (mg/L) | Standard Deviation 113.351 |
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.
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 + Risankizumab | Change From Baseline in Creatinine | Day 3 | 0.000 mg/dL | Standard Deviation 0.332 |
| Remdesivir + Risankizumab | Change From Baseline in Creatinine | Day 5 | -0.041 mg/dL | Standard Deviation 0.306 |
| Remdesivir + Risankizumab | Change From Baseline in Creatinine | Day 8 | -0.023 mg/dL | Standard Deviation 0.281 |
| Remdesivir + Risankizumab | Change From Baseline in Creatinine | Day 11 | -0.127 mg/dL | Standard Deviation 0.371 |
| Remdesivir + Risankizumab | Change From Baseline in Creatinine | Day 15 | -0.096 mg/dL | Standard Deviation 0.347 |
| Remdesivir + Risankizumab | Change From Baseline in Creatinine | Day 29 | -0.023 mg/dL | Standard Deviation 0.249 |
| Remdesivir + Placebo | Change From Baseline in Creatinine | Day 15 | 0.362 mg/dL | Standard Deviation 1.172 |
| Remdesivir + Placebo | Change From Baseline in Creatinine | Day 3 | -0.858 mg/dL | Standard Deviation 8.777 |
| Remdesivir + Placebo | Change From Baseline in Creatinine | Day 11 | -3.044 mg/dL | Standard Deviation 16.911 |
| Remdesivir + Placebo | Change From Baseline in Creatinine | Day 5 | -1.091 mg/dL | Standard Deviation 10.138 |
| Remdesivir + Placebo | Change From Baseline in Creatinine | Day 29 | 0.211 mg/dL | Standard Deviation 1.148 |
| Remdesivir + Placebo | Change From Baseline in Creatinine | Day 8 | -1.993 mg/dL | Standard Deviation 13.677 |
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.
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 + Risankizumab | Change From Baseline in D-dimer | Day 3 | -1642.4 ug/L fibrinogen equivalent units (FEU) | Standard Deviation 12710.1 |
| Remdesivir + Risankizumab | Change From Baseline in D-dimer | Day 5 | -914.1 ug/L fibrinogen equivalent units (FEU) | Standard Deviation 21635.7 |
| Remdesivir + Risankizumab | Change From Baseline in D-dimer | Day 8 | -4124.4 ug/L fibrinogen equivalent units (FEU) | Standard Deviation 23690 |
| Remdesivir + Risankizumab | Change From Baseline in D-dimer | Day 11 | -10670.7 ug/L fibrinogen equivalent units (FEU) | Standard Deviation 34100.4 |
| Remdesivir + Risankizumab | Change From Baseline in D-dimer | Day 15 | -8990.9 ug/L fibrinogen equivalent units (FEU) | Standard Deviation 28348.8 |
| Remdesivir + Risankizumab | Change From Baseline in D-dimer | Day 29 | -6516.8 ug/L fibrinogen equivalent units (FEU) | Standard Deviation 20705.8 |
| Remdesivir + Placebo | Change From Baseline in D-dimer | Day 15 | 907.1 ug/L fibrinogen equivalent units (FEU) | Standard Deviation 8625 |
| Remdesivir + Placebo | Change From Baseline in D-dimer | Day 3 | -38.8 ug/L fibrinogen equivalent units (FEU) | Standard Deviation 3315.6 |
| Remdesivir + Placebo | Change From Baseline in D-dimer | Day 11 | -741.2 ug/L fibrinogen equivalent units (FEU) | Standard Deviation 5094.4 |
| Remdesivir + Placebo | Change From Baseline in D-dimer | Day 5 | -129.3 ug/L fibrinogen equivalent units (FEU) | Standard Deviation 4104.4 |
| Remdesivir + Placebo | Change From Baseline in D-dimer | Day 29 | -471.8 ug/L fibrinogen equivalent units (FEU) | Standard Deviation 2401 |
| Remdesivir + Placebo | Change From Baseline in D-dimer | Day 8 | -38.9 ug/L fibrinogen equivalent units (FEU) | Standard Deviation 19399.8 |
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.
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 + Risankizumab | Change From Baseline in Eosinophils | Day 3 | 0.0009 10^9 cells/L | Standard Deviation 0.035 |
| Remdesivir + Risankizumab | Change From Baseline in Eosinophils | Day 5 | 0.0297 10^9 cells/L | Standard Deviation 0.0615 |
| Remdesivir + Risankizumab | Change From Baseline in Eosinophils | Day 8 | 0.0810 10^9 cells/L | Standard Deviation 0.0969 |
| Remdesivir + Risankizumab | Change From Baseline in Eosinophils | Day 11 | 0.1282 10^9 cells/L | Standard Deviation 0.1387 |
| Remdesivir + Risankizumab | Change From Baseline in Eosinophils | Day 15 | 0.0924 10^9 cells/L | Standard Deviation 0.0902 |
| Remdesivir + Risankizumab | Change From Baseline in Eosinophils | Day 29 | 0.1256 10^9 cells/L | Standard Deviation 0.0955 |
| Remdesivir + Placebo | Change From Baseline in Eosinophils | Day 15 | 0.1761 10^9 cells/L | Standard Deviation 0.1577 |
| Remdesivir + Placebo | Change From Baseline in Eosinophils | Day 3 | 0.0062 10^9 cells/L | Standard Deviation 0.0557 |
| Remdesivir + Placebo | Change From Baseline in Eosinophils | Day 11 | 0.0814 10^9 cells/L | Standard Deviation 0.0953 |
| Remdesivir + Placebo | Change From Baseline in Eosinophils | Day 5 | 0.0221 10^9 cells/L | Standard Deviation 0.0699 |
| Remdesivir + Placebo | Change From Baseline in Eosinophils | Day 29 | 0.3421 10^9 cells/L | Standard Deviation 0.3291 |
| Remdesivir + Placebo | Change From Baseline in Eosinophils | Day 8 | 0.0259 10^9 cells/L | Standard Deviation 0.0717 |
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.
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 + Risankizumab | Change From Baseline in Ferritin | Day 3 | -187.123 micrograms/liter (ug/L) | Standard Deviation 437.096 |
| Remdesivir + Risankizumab | Change From Baseline in Ferritin | Day 5 | -326.691 micrograms/liter (ug/L) | Standard Deviation 610.633 |
| Remdesivir + Risankizumab | Change From Baseline in Ferritin | Day 8 | -252.804 micrograms/liter (ug/L) | Standard Deviation 754.932 |
| Remdesivir + Risankizumab | Change From Baseline in Ferritin | Day 11 | -90.829 micrograms/liter (ug/L) | Standard Deviation 648.972 |
| Remdesivir + Risankizumab | Change From Baseline in Ferritin | Day 15 | -305.970 micrograms/liter (ug/L) | Standard Deviation 941.21 |
| Remdesivir + Risankizumab | Change From Baseline in Ferritin | Day 29 | -520.237 micrograms/liter (ug/L) | Standard Deviation 476.899 |
| Remdesivir + Placebo | Change From Baseline in Ferritin | Day 15 | -317.063 micrograms/liter (ug/L) | Standard Deviation 828.814 |
| Remdesivir + Placebo | Change From Baseline in Ferritin | Day 3 | -145.201 micrograms/liter (ug/L) | Standard Deviation 562.15 |
| Remdesivir + Placebo | Change From Baseline in Ferritin | Day 11 | -371.682 micrograms/liter (ug/L) | Standard Deviation 628.049 |
| Remdesivir + Placebo | Change From Baseline in Ferritin | Day 5 | -37.041 micrograms/liter (ug/L) | Standard Deviation 1956.1 |
| Remdesivir + Placebo | Change From Baseline in Ferritin | Day 29 | -762.394 micrograms/liter (ug/L) | Standard Deviation 1056.614 |
| Remdesivir + Placebo | Change From Baseline in Ferritin | Day 8 | -236.725 micrograms/liter (ug/L) | Standard Deviation 800.878 |
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.
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 + Risankizumab | Change From Baseline in Fibrinogen | Day 3 | -89.7 milligrams/deciliter (mg/dL) | Standard Deviation 124.9 |
| Remdesivir + Risankizumab | Change From Baseline in Fibrinogen | Day 5 | -109.0 milligrams/deciliter (mg/dL) | Standard Deviation 169.3 |
| Remdesivir + Risankizumab | Change From Baseline in Fibrinogen | Day 8 | -100.5 milligrams/deciliter (mg/dL) | Standard Deviation 218.2 |
| Remdesivir + Risankizumab | Change From Baseline in Fibrinogen | Day 11 | 61.1 milligrams/deciliter (mg/dL) | Standard Deviation 319.3 |
| Remdesivir + Risankizumab | Change From Baseline in Fibrinogen | Day 15 | -37.6 milligrams/deciliter (mg/dL) | Standard Deviation 235.1 |
| Remdesivir + Risankizumab | Change From Baseline in Fibrinogen | Day 29 | -99.3 milligrams/deciliter (mg/dL) | Standard Deviation 208.1 |
| Remdesivir + Placebo | Change From Baseline in Fibrinogen | Day 15 | -26.3 milligrams/deciliter (mg/dL) | Standard Deviation 181.6 |
| Remdesivir + Placebo | Change From Baseline in Fibrinogen | Day 3 | -78.6 milligrams/deciliter (mg/dL) | Standard Deviation 109.6 |
| Remdesivir + Placebo | Change From Baseline in Fibrinogen | Day 11 | -33.2 milligrams/deciliter (mg/dL) | Standard Deviation 282.7 |
| Remdesivir + Placebo | Change From Baseline in Fibrinogen | Day 5 | -108.8 milligrams/deciliter (mg/dL) | Standard Deviation 165.1 |
| Remdesivir + Placebo | Change From Baseline in Fibrinogen | Day 29 | -102.0 milligrams/deciliter (mg/dL) | Standard Deviation 185.6 |
| Remdesivir + Placebo | Change From Baseline in Fibrinogen | Day 8 | -121.0 milligrams/deciliter (mg/dL) | Standard Deviation 225.5 |
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.
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 + Risankizumab | Change From Baseline in Hemoglobin | Day 3 | -0.199 g/dL | Standard Deviation 0.785 |
| Remdesivir + Risankizumab | Change From Baseline in Hemoglobin | Day 5 | -0.485 g/dL | Standard Deviation 1.142 |
| Remdesivir + Risankizumab | Change From Baseline in Hemoglobin | Day 8 | -0.461 g/dL | Standard Deviation 1.434 |
| Remdesivir + Risankizumab | Change From Baseline in Hemoglobin | Day 11 | -1.079 g/dL | Standard Deviation 1.997 |
| Remdesivir + Risankizumab | Change From Baseline in Hemoglobin | Day 15 | -0.817 g/dL | Standard Deviation 1.702 |
| Remdesivir + Risankizumab | Change From Baseline in Hemoglobin | Day 29 | -0.524 g/dL | Standard Deviation 1.989 |
| Remdesivir + Placebo | Change From Baseline in Hemoglobin | Day 15 | -0.805 g/dL | Standard Deviation 1.929 |
| Remdesivir + Placebo | Change From Baseline in Hemoglobin | Day 3 | -0.035 g/dL | Standard Deviation 0.893 |
| Remdesivir + Placebo | Change From Baseline in Hemoglobin | Day 11 | -0.714 g/dL | Standard Deviation 1.722 |
| Remdesivir + Placebo | Change From Baseline in Hemoglobin | Day 5 | -0.074 g/dL | Standard Deviation 1.202 |
| Remdesivir + Placebo | Change From Baseline in Hemoglobin | Day 29 | -0.642 g/dL | Standard Deviation 1.867 |
| Remdesivir + Placebo | Change From Baseline in Hemoglobin | Day 8 | -0.323 g/dL | Standard Deviation 1.46 |
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.
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 + Risankizumab | Change From Baseline in International Normalized Ratio (INR) | Day 3 | 0.063 Ratio | Standard Deviation 0.174 |
| Remdesivir + Risankizumab | Change From Baseline in International Normalized Ratio (INR) | Day 5 | 0.103 Ratio | Standard Deviation 0.257 |
| Remdesivir + Risankizumab | Change From Baseline in International Normalized Ratio (INR) | Day 8 | 0.038 Ratio | Standard Deviation 0.206 |
| Remdesivir + Risankizumab | Change From Baseline in International Normalized Ratio (INR) | Day 11 | 0.137 Ratio | Standard Deviation 0.525 |
| Remdesivir + Risankizumab | Change From Baseline in International Normalized Ratio (INR) | Day 15 | -0.092 Ratio | Standard Deviation 0.238 |
| Remdesivir + Risankizumab | Change From Baseline in International Normalized Ratio (INR) | Day 29 | -0.129 Ratio | Standard Deviation 0.185 |
| Remdesivir + Placebo | Change From Baseline in International Normalized Ratio (INR) | Day 15 | -0.077 Ratio | Standard Deviation 0.164 |
| Remdesivir + Placebo | Change From Baseline in International Normalized Ratio (INR) | Day 3 | 0.069 Ratio | Standard Deviation 0.257 |
| Remdesivir + Placebo | Change From Baseline in International Normalized Ratio (INR) | Day 11 | 0.015 Ratio | Standard Deviation 0.249 |
| Remdesivir + Placebo | Change From Baseline in International Normalized Ratio (INR) | Day 5 | 0.174 Ratio | Standard Deviation 0.682 |
| Remdesivir + Placebo | Change From Baseline in International Normalized Ratio (INR) | Day 29 | -0.075 Ratio | Standard Deviation 0.141 |
| Remdesivir + Placebo | Change From Baseline in International Normalized Ratio (INR) | Day 8 | 0.277 Ratio | Standard Deviation 1.58 |
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.
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 + Risankizumab | Change From Baseline in Lymphocytes | Day 3 | 0.2788 10^9 cells/L | Standard Deviation 0.456 |
| Remdesivir + Risankizumab | Change From Baseline in Lymphocytes | Day 5 | 0.4256 10^9 cells/L | Standard Deviation 0.6067 |
| Remdesivir + Risankizumab | Change From Baseline in Lymphocytes | Day 8 | 0.3956 10^9 cells/L | Standard Deviation 0.6478 |
| Remdesivir + Risankizumab | Change From Baseline in Lymphocytes | Day 11 | 0.4431 10^9 cells/L | Standard Deviation 0.5793 |
| Remdesivir + Risankizumab | Change From Baseline in Lymphocytes | Day 15 | 0.7937 10^9 cells/L | Standard Deviation 0.6577 |
| Remdesivir + Risankizumab | Change From Baseline in Lymphocytes | Day 29 | 0.8309 10^9 cells/L | Standard Deviation 0.5085 |
| Remdesivir + Placebo | Change From Baseline in Lymphocytes | Day 15 | 0.6096 10^9 cells/L | Standard Deviation 0.7233 |
| Remdesivir + Placebo | Change From Baseline in Lymphocytes | Day 3 | 0.3009 10^9 cells/L | Standard Deviation 0.5398 |
| Remdesivir + Placebo | Change From Baseline in Lymphocytes | Day 11 | 0.2932 10^9 cells/L | Standard Deviation 0.6446 |
| Remdesivir + Placebo | Change From Baseline in Lymphocytes | Day 5 | 0.4233 10^9 cells/L | Standard Deviation 0.7375 |
| Remdesivir + Placebo | Change From Baseline in Lymphocytes | Day 29 | 0.7879 10^9 cells/L | Standard Deviation 0.581 |
| Remdesivir + Placebo | Change From Baseline in Lymphocytes | Day 8 | 0.2612 10^9 cells/L | Standard Deviation 0.6765 |
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.
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 + Risankizumab | Change From Baseline in Monocytes | Day 3 | 0.1697 10^9 cells/L | Standard Deviation 0.3201 |
| Remdesivir + Risankizumab | Change From Baseline in Monocytes | Day 5 | 0.2023 10^9 cells/L | Standard Deviation 0.3254 |
| Remdesivir + Risankizumab | Change From Baseline in Monocytes | Day 8 | 0.3398 10^9 cells/L | Standard Deviation 0.4427 |
| Remdesivir + Risankizumab | Change From Baseline in Monocytes | Day 11 | 0.2450 10^9 cells/L | Standard Deviation 0.2887 |
| Remdesivir + Risankizumab | Change From Baseline in Monocytes | Day 15 | 0.1694 10^9 cells/L | Standard Deviation 0.3182 |
| Remdesivir + Risankizumab | Change From Baseline in Monocytes | Day 29 | -0.0175 10^9 cells/L | Standard Deviation 0.2896 |
| Remdesivir + Placebo | Change From Baseline in Monocytes | Day 15 | 0.1407 10^9 cells/L | Standard Deviation 0.6706 |
| Remdesivir + Placebo | Change From Baseline in Monocytes | Day 3 | 0.1023 10^9 cells/L | Standard Deviation 0.502 |
| Remdesivir + Placebo | Change From Baseline in Monocytes | Day 11 | 0.1835 10^9 cells/L | Standard Deviation 0.8518 |
| Remdesivir + Placebo | Change From Baseline in Monocytes | Day 5 | 0.1318 10^9 cells/L | Standard Deviation 0.5708 |
| Remdesivir + Placebo | Change From Baseline in Monocytes | Day 29 | -0.0232 10^9 cells/L | Standard Deviation 0.7208 |
| Remdesivir + Placebo | Change From Baseline in Monocytes | Day 8 | 0.1135 10^9 cells/L | Standard Deviation 0.7707 |
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.
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 + Risankizumab | Change From Baseline in Neutrophils | Day 3 | 1.0297 10^9 cells/L | Standard Deviation 2.6919 |
| Remdesivir + Risankizumab | Change From Baseline in Neutrophils | Day 5 | 1.1050 10^9 cells/L | Standard Deviation 2.6733 |
| Remdesivir + Risankizumab | Change From Baseline in Neutrophils | Day 8 | 2.8066 10^9 cells/L | Standard Deviation 3.1523 |
| Remdesivir + Risankizumab | Change From Baseline in Neutrophils | Day 11 | 4.0192 10^9 cells/L | Standard Deviation 5.5099 |
| Remdesivir + Risankizumab | Change From Baseline in Neutrophils | Day 15 | -0.5410 10^9 cells/L | Standard Deviation 2.9101 |
| Remdesivir + Risankizumab | Change From Baseline in Neutrophils | Day 29 | -1.8493 10^9 cells/L | Standard Deviation 3.3028 |
| Remdesivir + Placebo | Change From Baseline in Neutrophils | Day 15 | 0.1833 10^9 cells/L | Standard Deviation 3.5524 |
| Remdesivir + Placebo | Change From Baseline in Neutrophils | Day 3 | 0.9628 10^9 cells/L | Standard Deviation 3.0963 |
| Remdesivir + Placebo | Change From Baseline in Neutrophils | Day 11 | 2.4704 10^9 cells/L | Standard Deviation 4.7446 |
| Remdesivir + Placebo | Change From Baseline in Neutrophils | Day 5 | 1.3373 10^9 cells/L | Standard Deviation 3.358 |
| Remdesivir + Placebo | Change From Baseline in Neutrophils | Day 29 | -2.6216 10^9 cells/L | Standard Deviation 3.8118 |
| Remdesivir + Placebo | Change From Baseline in Neutrophils | Day 8 | 4.1114 10^9 cells/L | Standard Deviation 5.5771 |
Secondary
Change From Baseline in Platelets
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.
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 + Risankizumab | Change From Baseline in Platelets | Day 3 | 59.49 10^9 cells/L | Standard Deviation 48.59 |
| Remdesivir + Risankizumab | Change From Baseline in Platelets | Day 5 | 81.22 10^9 cells/L | Standard Deviation 65.53 |
| Remdesivir + Risankizumab | Change From Baseline in Platelets | Day 8 | 96.73 10^9 cells/L | Standard Deviation 106.11 |
| Remdesivir + Risankizumab | Change From Baseline in Platelets | Day 11 | 54.95 10^9 cells/L | Standard Deviation 109.38 |
| Remdesivir + Risankizumab | Change From Baseline in Platelets | Day 15 | -16.90 10^9 cells/L | Standard Deviation 110.76 |
| Remdesivir + Risankizumab | Change From Baseline in Platelets | Day 29 | 27.42 10^9 cells/L | Standard Deviation 128.22 |
| Remdesivir + Placebo | Change From Baseline in Platelets | Day 15 | -24.19 10^9 cells/L | Standard Deviation 120.42 |
| Remdesivir + Placebo | Change From Baseline in Platelets | Day 3 | 50.45 10^9 cells/L | Standard Deviation 60.91 |
| Remdesivir + Placebo | Change From Baseline in Platelets | Day 11 | -1.68 10^9 cells/L | Standard Deviation 117.94 |
| Remdesivir + Placebo | Change From Baseline in Platelets | Day 5 | 76.17 10^9 cells/L | Standard Deviation 80.11 |
| Remdesivir + Placebo | Change From Baseline in Platelets | Day 29 | 45.97 10^9 cells/L | Standard Deviation 111.2 |
| Remdesivir + Placebo | Change From Baseline in Platelets | Day 8 | 71.59 10^9 cells/L | Standard Deviation 139.53 |
Secondary
Change From Baseline in White Blood Cell (WBC)
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.
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 + Risankizumab | Change From Baseline in White Blood Cell (WBC) | Day 3 | 1.672 10^9 cells/L | Standard Deviation 3.589 |
| Remdesivir + Risankizumab | Change From Baseline in White Blood Cell (WBC) | Day 5 | 2.484 10^9 cells/L | Standard Deviation 4.053 |
| Remdesivir + Risankizumab | Change From Baseline in White Blood Cell (WBC) | Day 8 | 3.726 10^9 cells/L | Standard Deviation 3.781 |
| Remdesivir + Risankizumab | Change From Baseline in White Blood Cell (WBC) | Day 11 | 4.852 10^9 cells/L | Standard Deviation 6.784 |
| Remdesivir + Risankizumab | Change From Baseline in White Blood Cell (WBC) | Day 15 | 1.770 10^9 cells/L | Standard Deviation 5.869 |
| Remdesivir + Risankizumab | Change From Baseline in White Blood Cell (WBC) | Day 29 | -0.801 10^9 cells/L | Standard Deviation 4.355 |
| Remdesivir + Placebo | Change From Baseline in White Blood Cell (WBC) | Day 15 | 1.663 10^9 cells/L | Standard Deviation 5.882 |
| Remdesivir + Placebo | Change From Baseline in White Blood Cell (WBC) | Day 3 | 1.432 10^9 cells/L | Standard Deviation 3.453 |
| Remdesivir + Placebo | Change From Baseline in White Blood Cell (WBC) | Day 11 | 4.545 10^9 cells/L | Standard Deviation 7.772 |
| Remdesivir + Placebo | Change From Baseline in White Blood Cell (WBC) | Day 5 | 2.437 10^9 cells/L | Standard Deviation 4.231 |
| Remdesivir + Placebo | Change From Baseline in White Blood Cell (WBC) | Day 29 | -2.016 10^9 cells/L | Standard Deviation 4.645 |
| Remdesivir + Placebo | Change From Baseline in White Blood Cell (WBC) | Day 8 | 5.298 10^9 cells/L | Standard Deviation 6.39 |
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 modified intention-to-treat (mITT) population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies, analyzed as randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remdesivir + Risankizumab | 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 Invasive Mechanical Ventilation / 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 modified intention-to-treat (mITT) population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies, analyzed as randomized. Only participants not on invasive ventilation/ECMO at baseline were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remdesivir + Risankizumab | Days of New Invasive Mechanical Ventilation / Extracorporeal Membrane Oxygenation (ECMO) Use | 0.0 days |
| Remdesivir + Placebo | Days of New Invasive Mechanical Ventilation / 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 modified intention-to-treat (mITT) population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies, analyzed as randomized. Only participants in the hospitalized requiring new or increased supplemental oxygen ordinal scale or below at baseline were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remdesivir + Risankizumab | 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 modified intention-to-treat (mITT) population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies, analyzed as randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remdesivir + Risankizumab | Days of Non-invasive Ventilation/High Flow Oxygen Use | 0.0 days |
| Remdesivir + Placebo | Days of Non-invasive Ventilation/High Flow Oxygen Use | 0.0 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 modified intention-to-treat (mITT) population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies, analyzed as randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remdesivir + Risankizumab | Days of Supplemental Oxygen Use | 11.0 days |
| Remdesivir + Placebo | Days of Supplemental Oxygen Use | 11.0 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 modified intention-to-treat (mITT) population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies, analyzed as randomized.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Remdesivir + Risankizumab | Duration of Hospitalization | Hospitalized for COVID-19 | 6.0 days |
| Remdesivir + Risankizumab | Duration of Hospitalization | Hospitalized for Any Reason | 6.0 days |
| Remdesivir + Placebo | Duration of Hospitalization | Hospitalized for COVID-19 | 6.0 days |
| Remdesivir + Placebo | Duration of Hospitalization | Hospitalized for Any Reason | 6.0 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 high-flow 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: Day 1, 3, 5, 11, 15, 22, 29
Population: The modified intention-to-treat (mITT) population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies, analyzed as randomized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Remdesivir + Risankizumab | Mean Change in Ordinal Scale | Day 3 | 0.0 units on a scale | Standard Deviation 0.5 |
| Remdesivir + Risankizumab | Mean Change in Ordinal Scale | Day 15 | -2.7 units on a scale | Standard Deviation 1.9 |
| Remdesivir + Risankizumab | Mean Change in Ordinal Scale | Day 8 | -1.7 units on a scale | Standard Deviation 1.9 |
| Remdesivir + Risankizumab | Mean Change in Ordinal Scale | Day 22 | -3.1 units on a scale | Standard Deviation 1.9 |
| Remdesivir + Risankizumab | Mean Change in Ordinal Scale | Day 5 | -0.5 units on a scale | Standard Deviation 1.3 |
| Remdesivir + Risankizumab | Mean Change in Ordinal Scale | Day 29 | -3.2 units on a scale | Standard Deviation 1.9 |
| Remdesivir + Risankizumab | Mean Change in Ordinal Scale | Day 11 | -2.2 units on a scale | Standard Deviation 1.9 |
| Remdesivir + Placebo | Mean Change in Ordinal Scale | Day 29 | -2.9 units on a scale | Standard Deviation 1.9 |
| Remdesivir + Placebo | Mean Change in Ordinal Scale | Day 5 | -0.4 units on a scale | Standard Deviation 1.2 |
| Remdesivir + Placebo | Mean Change in Ordinal Scale | Day 8 | -1.7 units on a scale | Standard Deviation 2 |
| Remdesivir + Placebo | Mean Change in Ordinal Scale | Day 11 | -2.1 units on a scale | Standard Deviation 2 |
| Remdesivir + Placebo | Mean Change in Ordinal Scale | Day 15 | -2.6 units on a scale | Standard Deviation 1.9 |
| Remdesivir + Placebo | Mean Change in Ordinal Scale | Day 22 | -2.8 units on a scale | Standard Deviation 1.8 |
| Remdesivir + Placebo | Mean Change in Ordinal Scale | Day 3 | 0.0 units on a scale | Standard Deviation 0.4 |
Secondary
Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15
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 high-flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.
Time frame: Day 15
Population: The modified intention-to-treat (mITT) population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies, analyzed as randomized.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Remdesivir + Risankizumab | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15 | Not hospitalized, no new or increased limitations on activities | 31 Participants |
| Remdesivir + Risankizumab | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15 | Not hosp., but new or incr. limit on activities and/or req. new or incr. home O2, CPAP, or BiPAP | 46 Participants |
| Remdesivir + Risankizumab | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15 | Hospitalized, not req new or increased supplemental O2 - no longer req ongoing medical care | 0 Participants |
| Remdesivir + Risankizumab | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15 | Hospitalized, not req new or increased supplemental O2 - req ongoing medical care | 1 Participants |
| Remdesivir + Risankizumab | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15 | Hospitalized, requiring new or increased supplemental O2 | 10 Participants |
| Remdesivir + Risankizumab | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15 | Hospitalized, requiring new or increased non-invasive ventilation or high-flow oxygen devices | 2 Participants |
| Remdesivir + Risankizumab | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15 | Hospitalized, on invasive mechanical ventilation or ECMO | 4 Participants |
| Remdesivir + Risankizumab | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15 | Death | 6 Participants |
| Remdesivir + Placebo | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15 | Death | 3 Participants |
| Remdesivir + Placebo | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15 | Not hospitalized, no new or increased limitations on activities | 37 Participants |
| Remdesivir + Placebo | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15 | Hospitalized, requiring new or increased supplemental O2 | 10 Participants |
| Remdesivir + Placebo | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15 | Not hosp., but new or incr. limit on activities and/or req. new or incr. home O2, CPAP, or BiPAP | 42 Participants |
| Remdesivir + Placebo | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15 | Hospitalized, on invasive mechanical ventilation or ECMO | 9 Participants |
| Remdesivir + Placebo | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15 | 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 15 | Hospitalized, requiring new or increased non-invasive ventilation or high-flow oxygen devices | 4 Participants |
| Remdesivir + Placebo | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15 | Hospitalized, not req new or increased supplemental O2 - req ongoing medical care | 2 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 last observation carried forward for those lost to follow-up before Day 15 while hospitalized, in hospice, long term acute care, or transferred to other hospital. Participants lost to follow-up before Day 15 after discharge are given a score of 2.p-value: 0.9195% CI: [0.62, 1.71]Proportional odds model
Secondary
Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 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 high-flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.
Time frame: Day 29
Population: The modified intention-to-treat (mITT) population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies, analyzed as randomized.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Remdesivir + Risankizumab | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29 | Not hospitalized, no new or increased limitations on activities | 46 Participants |
| Remdesivir + Risankizumab | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29 | Not hosp., but new or incr. limit on activities and/or req. new or incr. home O2, CPAP, or BiPAP | 43 Participants |
| Remdesivir + Risankizumab | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29 | Hospitalized, not req new or increased supplemental O2 - no longer req ongoing medical care | 0 Participants |
| Remdesivir + Risankizumab | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29 | Hospitalized, not req new or increased supplemental O2 - req ongoing medical care | 0 Participants |
| Remdesivir + Risankizumab | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29 | Hospitalized, requiring new or increased supplemental O2 | 0 Participants |
| Remdesivir + Risankizumab | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29 | Hospitalized, requiring new or increased non-invasive ventilation or high-flow oxygen devices | 0 Participants |
| Remdesivir + Risankizumab | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29 | Hospitalized, on invasive mechanical ventilation or ECMO | 4 Participants |
| Remdesivir + Risankizumab | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29 | Death | 7 Participants |
| Remdesivir + Placebo | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29 | Death | 7 Participants |
| Remdesivir + Placebo | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29 | Not hospitalized, no new or increased limitations on activities | 50 Participants |
| Remdesivir + Placebo | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29 | Hospitalized, requiring new or increased supplemental O2 | 3 Participants |
| Remdesivir + Placebo | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29 | Not hosp., but new or incr. limit on activities and/or req. new or incr. home O2, CPAP, or BiPAP | 38 Participants |
| Remdesivir + Placebo | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29 | Hospitalized, on invasive mechanical ventilation or ECMO | 4 Participants |
| Remdesivir + Placebo | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29 | 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 29 | Hospitalized, requiring new or increased non-invasive ventilation or high-flow oxygen devices | 4 Participants |
| Remdesivir + Placebo | Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29 | Hospitalized, not req new or increased supplemental O2 - req ongoing medical care | 1 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 last observation carried forward for those lost to follow-up before Day 15 while hospitalized, in hospice, long term acute care, or transferred to other hospital. Participants lost to follow-up before Day 15 after discharge are given a score of 2.p-value: 0.61795% CI: [0.68, 1.93]Proportional odds model
Secondary
Number of Participants Reporting Grade 3 and 4 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.
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 + Risankizumab | Number of Participants Reporting Grade 3 and 4 Clinical and/or Laboratory Adverse Events (AEs) | 42 Participants |
| Remdesivir + Placebo | Number of Participants Reporting Grade 3 and 4 Clinical and/or Laboratory Adverse Events (AEs) | 46 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 + Risankizumab | Number of Participants Reporting Serious Adverse Events (SAEs) | 24 Participants |
| Remdesivir + Placebo | Number of Participants Reporting Serious Adverse Events (SAEs) | 26 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 + Risankizumab | Number of Participants Who Discontinued or Temporarily Suspended Study Treatment | 1 Participants |
| Remdesivir + Placebo | Number of Participants Who Discontinued or Temporarily Suspended Study Treatment | 0 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 modified intention-to-treat (mITT) population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies, analyzed as randomized. Only participants not on invasive ventilation/ECMO at baseline were included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Remdesivir + Risankizumab | Number of Participants With New Invasive Mechanical Ventilation / Extracorporeal Membrane Oxygenation (ECMO) Use | 12 Participants |
| Remdesivir + Placebo | Number of Participants With New Invasive Mechanical Ventilation / Extracorporeal Membrane Oxygenation (ECMO) Use | 12 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 non-invasive ventilation/high flow oxygen, invasive ventilation/ECMO or died during the study.
Time frame: Day 1 through Day 29
Population: The modified intention-to-treat (mITT) population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies, analyzed as randomized. Only participants in the hospitalized requiring new or increased supplemental oxygen ordinal scale or below at baseline were included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Remdesivir + Risankizumab | Number of Participants With New Non-invasive Ventilation/High Flow Oxygen Use | 10 Participants |
| Remdesivir + Placebo | Number of Participants With New Non-invasive Ventilation/High Flow Oxygen Use | 20 Participants |
Secondary
Proportion of Participants Not Meeting Criteria for One of Two Ordinal Scale Categories at Day 29
Ordinal scale categories include 8) Death and 7) Hospitalized, on Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO). 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 modified intention-to-treat (mITT) population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies, analyzed as randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Remdesivir + Risankizumab | Proportion of Participants Not Meeting Criteria for One of Two Ordinal Scale Categories at Day 29 | 0.89 Proportion of participants |
| Remdesivir + Placebo | Proportion of Participants Not Meeting Criteria for One of Two Ordinal Scale Categories at Day 29 | 0.90 Proportion of participants |
Secondary
Proportion of Participants Not Meeting Criteria for One of Two Ordinal Scale Categories Through Day 29
Ordinal scale categories include 8) Death and 7) Hospitalized, on Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO). 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. Results are reported as Kaplan Meier estimates.
Time frame: Day 1 through Day 29
Population: The modified intention-to-treat (mITT) population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies, analyzed as randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Remdesivir + Risankizumab | Proportion of Participants Not Meeting Criteria for One of Two Ordinal Scale Categories Through Day 29 | 0.87 Proportion of participants |
| Remdesivir + Placebo | Proportion of Participants Not Meeting Criteria for One of Two Ordinal Scale Categories Through Day 29 | 0.88 Proportion of participants |
Comparison: Odds ratio, confidence interval, and p-value estimated from a logistic regression model adjusted for baseline dexamethasone use, baseline ordinal score, age, and baseline C-Reactive Protein (CRP).p-value: 0.82995% CI: [0.36, 2.25]Regression, Logistic
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 non-invasive 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 modified intention-to-treat (mITT) population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies, analyzed as randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remdesivir + Risankizumab | Time to an Improvement of One Category From Baseline Using an Ordinal Scale | 6.0 days |
| Remdesivir + Placebo | Time to an Improvement of One Category From Baseline Using an Ordinal Scale | 7.0 days |
Comparison: Hazard ratio (HR), confidence interval, and p-value estimated from a Cox model adjusted for baseline steroid use and baseline ordinal score.p-value: 0.5595% CI: [0.82, 1.46]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 non-invasive 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 modified intention-to-treat (mITT) population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies, analyzed as randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remdesivir + Risankizumab | Time to an Improvement of Two Categories From Baseline Using an Ordinal Scale | 12.0 days |
| Remdesivir + Placebo | Time to an Improvement of Two Categories From Baseline Using an Ordinal Scale | 13.0 days |
Comparison: Hazard ratio (HR), confidence interval, and p-value estimated from a Cox model adjusted for baseline steroid use and baseline ordinal score.p-value: 0.52395% CI: [0.82, 1.48]Regression, Cox
Secondary
Time to Death
The time 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 + Risankizumab | Time to Death | NA days |
| Remdesivir + Placebo | Time to Death | NA days |
Secondary
Time to Sustained Recovery
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 modified intention-to-treat (mITT) population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies, analyzed as randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remdesivir + Risankizumab | Time to Sustained Recovery | 7.0 days |
| Remdesivir + Placebo | Time to Sustained Recovery | 6.0 days |
Comparison: Hazard ratio, confidence interval, and p-value estimated from a Cox model adjusted for baseline steroid use and baseline ordinal score.p-value: 0.39995% CI: [0.84, 1.56]Regression, Cox