Critical Confirmed Coronavirus Disease (COVID)-19
Conditions
Brief summary
The purpose of this study is to evaluate the clinical response of sirukumab (administered as a single intravenous dose) plus standard of care (SOC) compared to placebo plus SOC in COVID-19.
Detailed description
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is an enveloped, positive-sense, single-stranded ribonucleic acid (RNA) betacoronavirus. Symptoms of COVID-19 infection may appear from 2 to 14 days following exposure, with the spectrum of illnesses ranging from mild symptoms to severe illness or death. The identification of SARS-CoV-2 follows the emergence of 2 other novel betacoronaviruses: SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Current management of COVID-19 is supportive, and respiratory failure from acute respiratory distress syndrome (ARDS) is the leading cause of mortality. While an understanding of the epidemiology and clinical spectrum of COVID-19 is still evolving during the ongoing pandemic, the current knowledge of the disease burden highlights the urgent medical need to develop a treatment. Sirukumab (also known as CNTO136) is a human anti-interleukin (IL)-6 immunoglobulin G1 kappa (IgG1k) monoclonal antibody (mAb). Sirukumab binds with high affinity and specificity to human IL-6 and as a result inhibits IL-6-mediated signaling and the biological effects of IL-6. The study will include a Screening Phase (up to 1 Day), a Treatment Phase (Day 1 to Day 28) and a Follow-up Phase (post Day 28, follow-up phone calls on Week 8, Week 12 and Week 16). Safety evaluations will include monitoring of adverse events and serious adverse events, physical examinations, vital sign measurements, electrocardiograms, clinical laboratory tests, pregnancy testing, and checking of vital status. The entire study duration for each participant will be 16 weeks.
Interventions
DRUGSirukumab
Participants will receive single dose infusion of sirukumab on Day 1.
DRUGPlacebo
Participants will receive placebo IV single dose infusion on Day 1.
OTHERStandard of Care (SOC)
SOC treatment will be determined by the investigator based on local practice and consists of supportive care.
Sponsors
Janssen Pharmaceutica N.V., Belgium
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 84 Years
Healthy volunteers
No
Inclusion criteria
* Hospitalized * Has laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as determined by real time-polymerase chain reaction (PCR) at any time before randomization * Evidence of infiltrates by chest X-ray, chest computed tomography (CT), lung ultrasound, or chest auscultation (rales, crackles) * Informed consent must be obtained from the participant indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study * Critical COVID-19 disease, defined as: Requires supplemental oxygen delivered by nonrebreather mask or high-flow nasal cannula or use of non-invasive or invasive ventilation or requiring treatment in an intensive care unit 1. AND corresponding to category 4 on the 6-point ordinal recovery scale, that is: requires one of the above modalities to sustain a peripheral capillary oxygen saturation (SpO2) greater than (\>) 93 percent (%) with a fraction of inspired oxygen (FiO2) of 50% or higher. Note, the use of other devices may fit with category 4 if the FiO2 is 50% or higher. 2. OR, corresponding to category 5 on the 6-point ordinal recovery scale, that is partial pressure of oxygen in arterial per percentage of inspired oxygen (PaO2/FiO2) ratio \< 300 millimeter of mercury (mmHg) while on invasive mechanical ventilation or veno-venous extracorporeal membrane oxygenation (ECMO) for less than 48 hours prior to screening
Exclusion criteria
* On invasive mechanical ventilation or on veno-venous ECMO for \>48 hours at time of screening * Received an investigational intervention (including investigational vaccines) or used an invasive investigational medical device within 30 days before the planned dose of study intervention. Note: the investigator must ensure that the participant is not enrolled in another COVID-19 study with an investigational intervention (apart from the exception specified below) prior to completion of Day 28 of the current study. Exception: participation in a single arm study, a non-blinded controlled study, expanded access, compassionate use program or any other program that is not a blinded study is allowed if it is conducted with one of the following: agents with demonstrated in vitro-effect against SARSCoV- 2, as mentioned in the center of disease control and prevention (CDC) guidelines and convalescent plasma * Current confirmed or high suspicion for pulmonary embolus, hemodynamic significant pericardial effusion, myocarditis, or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification AND/OR Current evidence of active cardiac ischemia * Has a history of respiratory condition (that is, asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, fibrotic lung disease) that requires home oxygen supplementation, supportive non-invasive ventilation or, is status/post lung volume reduction surgery (LVRS). Exception: Participants with sleep apnea using supportive non-invasive ventilation (continuous positive airway pressure \[CPAP\]) at screening may be included * On renal replacement therapy (defined as peritoneal dialysis or hemodialysis) * Screening laboratory test result as follows: absolute neutrophil count (ANC) \<1.0\*10\^3 cells/microliter; Platelet count \<50\*10\^3 cells/microliter; estimated glomerular filtration rate (eGFR) \<=30 milliliter per minute per 1.73 square meter (mL/min/1.73 m\^2); Bilirubin \>2\* upper limit of normal (ULN) unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin; alanine aminotransferase/ aspartate aminotransferase (ALT) \>5\*ULN; Prothrombin time (PT)/international normalized ratio (INR) \>1.5\*ULN or activated partial thromboplastin time (aPTT) \>1.5\*ULN related to known coagulopathy or bleeding disorder (the participant can receive anticoagulant therapies for underlying conditions, or as systematic thromboprophylaxis due to COVID-19, or as part of the treatment of complications of COVID-19, but cannot participate in a clinical study with anticoagulants for COVID-19) * Pregnant or breastfeeding, unless in the opinion of the investigator, the benefit outweighs the risks * Has active hepatitis B or C infection or has human immunodeficiency virus infection or acquired immune deficiency syndrome (HIV/AIDS) based on medical history and/or concomitant medication * Known active or latent tuberculosis (TB), history of incompletely treated TB, suspected or known extrapulmonary TB based on medical history and/or concomitant medication * Evidence of active bacterial (including but not limited to bacterial pneumonia), fungal, viral or opportunistic infection (other than SARS-CoV-2) * Currently active clinically significant (example, causing hemodynamic instability and/or causing hypoxemia) and uncontrolled arrhythmia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Sustained Improvement of at Least 2 Categories on 6-point Ordinal Clinical Recovery Scale (CRS): Primary Analysis Set | Up to Day 28 | Time to sustained improvement is defined as an improvement of at least 2 categories relative to baseline on the 6-point ordinal clinical recovery scale sustained until Day 28. The 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6) corresponding to below categories, reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: not hospitalized, including participants on low level of oxygen (category 1); Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With All-cause Mortality Up to 28 Days | Up to 28 days | Percentage of participants with all-cause mortality up to 28 days were reported. All-cause mortality included all deaths of participants due to any cause. |
| Time to Sustained Improvement of at Least 2 Categories on 6-point Ordinal CRS: Intent-to-Treat (ITT) Set | Up to Day 28 | Time to sustained improvement is defined as an improvement of at least 2 categories relative to baseline on the 6-point ordinal clinical recovery scale, sustained until Day 28. The 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6) corresponding to below categories, reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: not hospitalized, including participants on low level of oxygen (category 1); Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening. |
| Percentage of Participants With an Improvement of at Least 2 Categories Compared to Baseline on 6-point Ordinal CRS: ITT Set | Day 28 | Percentage of participants with an improvement of at least 2 categories compared to baseline on 6-point ordinal CRS were reported. The 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6) corresponding to below categories, reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: not hospitalized, including participants on low level of oxygen (category 1); Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening. |
| Percentage of Participants With All-cause Mortality: ITT Set | Day 28 | Percentage of participants with all-cause mortality were reported. All-cause mortality included all deaths of participants due to any cause. |
| Percentage of Participants With Serious Adverse Events (SAEs) (Treatment Phase) | Up to Day 28 | Percentage of participants with SAEs were reported. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above. |
| Percentage of Participants With Related Adverse Events (AEs) | Up to Day 28 | Percentage of participants with related AEs were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. |
| Percentage of Participants With Severe or Life-threatening, Bacterial, Invasive Fungal, Viral or Opportunistic Infections | Up to Day 28 | Percentage of participants with severe or Life-threatening, bacterial, invasive fungal, viral or opportunistic infections were reported. |
| Percentage of Participants With Grade 3 and 4 Neutropenia and Lymphocytopenia | Up to Day 28 | Percentage of participants with Grade 3 and 4 neutropenia and lymphocytopenia were reported. The laboratory abnormalities were determined as per division of microbiology and infectious diseases (DMID) adult toxicity as Grade 1: mild (transient or mild discomfort \[less than {\<} 48 hours\]; no medical intervention/therapy required); Grade 2: moderate (mild to moderate limitation in activity - some assistance may be needed; no or minimal medical intervention/therapy required); Grade 3: severe (severe marked limitation in activity, some assistance usually required; medical intervention/therapy required, hospitalizations possible); Grade 4: life-threatening (extreme limitation in activity, significant assistance required; significant medical intervention/therapy required, hospitalization or hospice care probable). |
| Percentage of Participants With Increased Alanine Transaminase (ALT) Greater Than or Equal to (>=)3*Upper Limit Normal (ULN) Combined With Increased Bilirubin Greater Than (>)2*ULN | Up to Day 28 | Percentage of participants with increased ALT \>=3\*ULN combined with increased bilirubin \>2\*ULN were reported. |
| Time to Sustained Improvement of at Least 1 Category on 6-point Ordinal CRS: Primary Analysis Set | Up to Day 28 | Time to sustained improvement is defined as an improvement of at least 1 category relative to baseline on the 6-point ordinal clinical recovery scale, sustained until Day 28. The 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6) corresponding to below categories, reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: not hospitalized, including participants on low level of oxygen (category 1); Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening. |
| Time to Sustained Improvement of at Least 1 Category on 6-point Ordinal CRS: ITT Set | Up to Day 28 | Time to sustained improvement is defined as an improvement of at least 1 category relative to baseline on the 6-point ordinal clinical recovery scale, sustained until Day 28. The 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6) corresponding to below categories, reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: not hospitalized, including participants on low level of oxygen (category 1); Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening. |
| Percentage of Participants With an Improvement of at Least 1 Category Compared to Baseline on 6-point Ordinal CRS: Primary Analysis Set | Day 28 | The 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6), reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: (category 1) not hospitalized, including participants on low level of oxygen; Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening. |
| Percentage of Participants With an Improvement of at Least 1 Category on 6-point Ordinal CRS: ITT Set | Day 28 | The 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6) corresponding to below categories, reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: not hospitalized, including participants on low level of oxygen (category 1); Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening |
| Percentage of Participants With an Improvement of At Least 2 Categories Compared to Baseline on 6-point Ordinal CRS | Day 28 | Percentage of participants with an improvement of at least 2 Categories compared to baseline on 6-point ordinal CRS were reported. The 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6) corresponding to below categories, reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: not hospitalized, including participants on low level of oxygen (category 1); Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening. |
| Time From Study Intervention Administration to Hospital Discharge Among the Surviving Participants | Up to Day 28 | Time from study intervention administration to hospital discharge among the surviving participants was reported. |
| Total Length of Hospitalization Among the Surviving Participants | Up to Day 28 | Total length of hospitalization, defined as total duration of hospital stay, among the surviving participants was reported. |
| Number of Ventilation Free Days | Up to Day 28 | Number of ventilation free days in participants on invasive mechanical ventilation (IVM)/extracorporeal membrane oxygenation (ECMO) at baseline was reported. |
| Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | On Day 7, 14, 21, 28 | Percentage of participants with clinical status as assessed by 6-point Ordinal CRS were reported. The 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6) corresponding to below categories, reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: Not hospitalized, not requiring supplemental oxygen (category 1.1); Not hospitalized, requiring supplemental oxygen (category 1.2); Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening. |
| Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | On Days 7, 14, 21, 28 | Percentage of participants with clinical status as assessed by 6-point Ordinal CRS (ITT Set) were reported. The 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6) corresponding to below categories, reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: Not hospitalized, not requiring supplemental oxygen (category 1.1); Not hospitalized, requiring supplemental oxygen (category 1.2); Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening. |
| Total Time on Invasive Mechanical Ventilation | Up to Day 28 | Total time on invasive mechanical ventilation in participants who were on invasive mechanical ventilation at baseline was reported. |
| Percentage of Participants With a Worse Category Relative to Baseline on the 6-point Ordinal CRS | From Day 5 up to Day 28 | Percentage of participants with a worse category relative to baseline on the 6-point ordinal CRS for at least one of the daily assessment during the reporting period Day 5 and Day 28 were reported. he 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6) corresponding to below categories, reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: not hospitalized, including participants on low level of oxygen (category 1); Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening. |
| Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | From Day 1 up to Day 28 | Percentage of participants with ECMO over time were reported. |
| Total Time on ECMO | Up to Day 28 | Total time for participants on ECMO was reported. |
| Percentage of Alive Participants at Day 28, Week 8, and Week 16 | On Day 28, Week 8 and Week 16 | Percentage of alive participants at Day 28, Week 8, and Week 16 were reported. For this outcome measure, at Week 8, data was not collected for participants due to pandemic situation. |
| Percentage of Alive Participants That Required Readmission at Week 8, and Week 16 | Week 8 and Week 16 | Percentage of alive participants that required readmission at Week 8, and Week 16 were reported. For this outcome measure, at Week 8 and Week 16, data was not collected for participants due to pandemic situation. |
| Percentage of Participants With SAEs (Follow-up Phase) | From Week 4 up to Week 16 | Percentage of participants with SAEs were reported. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above. |
| Time From Study Intervention Administration to End of Oxygen Supplementation | Up to Day 28 | Time from study intervention administration to end of oxygen supplementation was reported. |
Countries
United States
Participant flow
Pre-assignment details
Out of 212 participants who started the study and got randomized, 209 participants (139 in Sirukumab + Standard of Care \[SOC\] and 70 in Placebo + SOC arm) were treated. Out of 212, 139 participants (96 in Sirukumab + SOC and 43 in Placebo + SOC arms) completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Sirukumab + SOC Hospitalized participants with confirmed severe or critical coronavirus disease-2019 (COVID-19) received intravenous (IV) single dose infusion of sirukumab (5 milligrams per kilogram \[mg/kg\]) on Day 1 along with standard of care (SOC) treatment per the discretion of the Investigator. | 139 |
| Placebo + SOC Hospitalized participants with confirmed severe or critical COVID-19 disease received IV single dose infusion of placebo on Day 1 along with SOC treatment per the discretion of the Investigator. | 70 |
| Total | 209 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 22 | 16 |
| Overall Study | Lost to Follow-up | 17 | 11 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Randomized but Not Treated | 1 | 2 |
| Overall Study | Withdrawal by Subject | 3 | 0 |
Baseline characteristics
| Characteristic | Sirukumab + SOC | Placebo + SOC | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 45 Participants | 22 Participants | 67 Participants |
| Age, Categorical Between 18 and 65 years | 94 Participants | 48 Participants | 142 Participants |
| Age, Continuous | 57.8 years STANDARD_DEVIATION 12.91 | 57.8 years STANDARD_DEVIATION 12.91 | 57.8 years STANDARD_DEVIATION 12.88 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 64 Participants | 36 Participants | 100 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 75 Participants | 34 Participants | 109 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 3 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 18 Participants | 11 Participants | 29 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 | 9 Participants | 5 Participants | 14 Participants |
| Race (NIH/OMB) White | 104 Participants | 51 Participants | 155 Participants |
| Region of Enrollment UNITED STATES | 139 Participants | 70 Participants | 209 Participants |
| Sex: Female, Male Female | 41 Participants | 25 Participants | 66 Participants |
| Sex: Female, Male Male | 98 Participants | 45 Participants | 143 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 18 / 139 | 4 / 118 | 13 / 70 | 3 / 57 |
| other Total, other adverse events | 24 / 139 | 1 / 118 | 16 / 70 | 1 / 57 |
| serious Total, serious adverse events | 35 / 139 | 7 / 118 | 22 / 70 | 3 / 57 |
Outcome results
Primary
Time to Sustained Improvement of at Least 2 Categories on 6-point Ordinal Clinical Recovery Scale (CRS): Primary Analysis Set
Time to sustained improvement is defined as an improvement of at least 2 categories relative to baseline on the 6-point ordinal clinical recovery scale sustained until Day 28. The 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6) corresponding to below categories, reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: not hospitalized, including participants on low level of oxygen (category 1); Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening.
Time frame: Up to Day 28
Population: The Primary Analysis Set consisted of all participants in the Intent-to-Treat (ITT) analysis set (which consisted of all participants who were randomized and treated in the study) with confirmed critical COVID-19 disease defined as score of 4 or 5 on the ordinal CRS at baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sirukumab + SOC | Time to Sustained Improvement of at Least 2 Categories on 6-point Ordinal Clinical Recovery Scale (CRS): Primary Analysis Set | 17.00 Days |
| Placebo + SOC | Time to Sustained Improvement of at Least 2 Categories on 6-point Ordinal Clinical Recovery Scale (CRS): Primary Analysis Set | 23.00 Days |
Secondary
Number of Ventilation Free Days
Number of ventilation free days in participants on invasive mechanical ventilation (IVM)/extracorporeal membrane oxygenation (ECMO) at baseline was reported.
Time frame: Up to Day 28
Population: The Primary Analysis Set restricted to participants who were on IVM/ECMO at baseline. Here, 'N' (Number of participants analyzed) included all participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sirukumab + SOC | Number of Ventilation Free Days | 13.82 Days | Standard Deviation 11.062 |
| Placebo + SOC | Number of Ventilation Free Days | 6.63 Days | Standard Deviation 9.546 |
Secondary
Percentage of Alive Participants at Day 28, Week 8, and Week 16
Percentage of alive participants at Day 28, Week 8, and Week 16 were reported. For this outcome measure, at Week 8, data was not collected for participants due to pandemic situation.
Time frame: On Day 28, Week 8 and Week 16
Population: The ITT analysis set consisted of all participants who were randomized and treated in the study. Here 'N' (number of participants analyzed) included all participants evaluable for this outcome measure. Here, 'n' (number analyzed) is defined as participants analyzed for specified timepoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sirukumab + SOC | Percentage of Alive Participants at Day 28, Week 8, and Week 16 | Day 28 | 86.8 Percentage of Participants |
| Sirukumab + SOC | Percentage of Alive Participants at Day 28, Week 8, and Week 16 | Week 16 | 81.3 Percentage of Participants |
| Placebo + SOC | Percentage of Alive Participants at Day 28, Week 8, and Week 16 | Day 28 | 81.4 Percentage of Participants |
| Placebo + SOC | Percentage of Alive Participants at Day 28, Week 8, and Week 16 | Week 16 | 72.9 Percentage of Participants |
Secondary
Percentage of Alive Participants That Required Readmission at Week 8, and Week 16
Percentage of alive participants that required readmission at Week 8, and Week 16 were reported. For this outcome measure, at Week 8 and Week 16, data was not collected for participants due to pandemic situation.
Time frame: Week 8 and Week 16
Population: The ITT analysis set consisted of all participants who were randomized and treated in the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Unknown | Percentage of Alive Participants That Required Readmission at Week 8, and Week 16 | Week 8 | — Percentage of Participants |
| Unknown | Percentage of Alive Participants That Required Readmission at Week 8, and Week 16 | Week 16 | — Percentage of Participants |
Secondary
Percentage of Participants With All-cause Mortality: ITT Set
Percentage of participants with all-cause mortality were reported. All-cause mortality included all deaths of participants due to any cause.
Time frame: Day 28
Population: The ITT analysis set consisted of all participants who were randomized and treated in the study. Here, 'N' (Number of participants analyzed) included all participants evaluable for this outcome measure. There were 3 participants in the 'Sirukumab + SOC arm' who discontinued the trial before Day 28 and thus were not evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sirukumab + SOC | Percentage of Participants With All-cause Mortality: ITT Set | 13.2 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With All-cause Mortality: ITT Set | 18.6 Percentage of Participants |
Secondary
Percentage of Participants With All-cause Mortality Up to 28 Days
Percentage of participants with all-cause mortality up to 28 days were reported. All-cause mortality included all deaths of participants due to any cause.
Time frame: Up to 28 days
Population: The Primary Analysis Set consisted of all participants in the ITT analysis set with confirmed critical COVID-19 disease defined as score of 4 or 5 on the ordinal CRS at baseline. Here, 'N' (Number of participants analyzed) included all participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sirukumab + SOC | Percentage of Participants With All-cause Mortality Up to 28 Days | 24.6 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With All-cause Mortality Up to 28 Days | 30.0 Percentage of Participants |
Secondary
Percentage of Participants With an Improvement of at Least 1 Category Compared to Baseline on 6-point Ordinal CRS: Primary Analysis Set
The 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6), reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: (category 1) not hospitalized, including participants on low level of oxygen; Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening.
Time frame: Day 28
Population: The Primary Analysis Set consisted of all participants in the ITT analysis set with confirmed critical COVID-19 disease defined as score of 4 or 5 on the ordinal CRS at baseline. Here, 'N' (Number of participants analyzed) included all participants evaluable for this outcome measure. There were 3 participants in the 'Sirukumab + SOC arm' who discontinued the trial before Day 28 and thus were not evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sirukumab + SOC | Percentage of Participants With an Improvement of at Least 1 Category Compared to Baseline on 6-point Ordinal CRS: Primary Analysis Set | 62.3 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With an Improvement of at Least 1 Category Compared to Baseline on 6-point Ordinal CRS: Primary Analysis Set | 57.5 Percentage of Participants |
Secondary
Percentage of Participants With an Improvement of at Least 1 Category on 6-point Ordinal CRS: ITT Set
The 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6) corresponding to below categories, reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: not hospitalized, including participants on low level of oxygen (category 1); Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening
Time frame: Day 28
Population: The ITT analysis set consisted of all participants who were randomized and treated in the study. Here, 'N' (Number of participants analyzed) included all participants evaluable for this outcome measure. There were 3 participants in the 'Sirukumab + SOC arm' who discontinued the trial before Day 28 and thus were not evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sirukumab + SOC | Percentage of Participants With an Improvement of at Least 1 Category on 6-point Ordinal CRS: ITT Set | 80.1 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With an Improvement of at Least 1 Category on 6-point Ordinal CRS: ITT Set | 74.3 Percentage of Participants |
Secondary
Percentage of Participants With an Improvement of At Least 2 Categories Compared to Baseline on 6-point Ordinal CRS
Percentage of participants with an improvement of at least 2 Categories compared to baseline on 6-point ordinal CRS were reported. The 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6) corresponding to below categories, reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: not hospitalized, including participants on low level of oxygen (category 1); Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening.
Time frame: Day 28
Population: The Primary Analysis Set consisted of all participants in the ITT analysis set with confirmed critical COVID-19 disease defined as score of 4 or 5 on the ordinal CRS at baseline. Here, 'N' (Number of participants analyzed) included all participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sirukumab + SOC | Percentage of Participants With an Improvement of At Least 2 Categories Compared to Baseline on 6-point Ordinal CRS | 59.4 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With an Improvement of At Least 2 Categories Compared to Baseline on 6-point Ordinal CRS | 55.0 Percentage of Participants |
Secondary
Percentage of Participants With an Improvement of at Least 2 Categories Compared to Baseline on 6-point Ordinal CRS: ITT Set
Percentage of participants with an improvement of at least 2 categories compared to baseline on 6-point ordinal CRS were reported. The 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6) corresponding to below categories, reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: not hospitalized, including participants on low level of oxygen (category 1); Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening.
Time frame: Day 28
Population: The ITT analysis set consisted of all participants who were randomized and treated in the study. Here, 'N' (Number of participants analyzed) included all participants evaluable for this outcome measure. There were 3 participants in the 'Sirukumab + SOC arm' who discontinued the trial before Day 28 and thus were not evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sirukumab + SOC | Percentage of Participants With an Improvement of at Least 2 Categories Compared to Baseline on 6-point Ordinal CRS: ITT Set | 77.9 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With an Improvement of at Least 2 Categories Compared to Baseline on 6-point Ordinal CRS: ITT Set | 70.0 Percentage of Participants |
Secondary
Percentage of Participants With a Worse Category Relative to Baseline on the 6-point Ordinal CRS
Percentage of participants with a worse category relative to baseline on the 6-point ordinal CRS for at least one of the daily assessment during the reporting period Day 5 and Day 28 were reported. he 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6) corresponding to below categories, reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: not hospitalized, including participants on low level of oxygen (category 1); Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening.
Time frame: From Day 5 up to Day 28
Population: The ITT analysis set consisted of all participants who were randomized and treated in the study. Here 'N' (number of participants analyzed) included all participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sirukumab + SOC | Percentage of Participants With a Worse Category Relative to Baseline on the 6-point Ordinal CRS | 25.0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With a Worse Category Relative to Baseline on the 6-point Ordinal CRS | 31.4 Percentage of Participants |
Secondary
Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set
Percentage of participants with clinical status as assessed by 6-point Ordinal CRS (ITT Set) were reported. The 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6) corresponding to below categories, reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: Not hospitalized, not requiring supplemental oxygen (category 1.1); Not hospitalized, requiring supplemental oxygen (category 1.2); Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening.
Time frame: On Days 7, 14, 21, 28
Population: The ITT analysis set consisted of all participants who were randomized and treated in the study. Here 'N' (number of participants analyzed) included all participants evaluable for this outcome measure. Here, 'n' (number analyzed) is defined as participants analyzed for specified categories at specified timepoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 28: Category 5 | 4.4 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 21: Category 2 | 0.7 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 28: Category 6 | 13.2 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 21: Category 6 | 8.1 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 7: Category 1.1 | 31.9 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 14: Category 6 | 6.6 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 7: Category 1.2 | 8.7 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 28: Category 1.1 | 48.5 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 7: Category 2 | 5.1 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 21: Category 3 | 5.1 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 7: Category 3 | 20.3 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 28: Category 1.2 | 28.7 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 7: Category 4 | 18.8 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 21: Category 1.2 | 27.9 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 7: Category 5 | 13.8 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 28: Category 2 | 0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 7: Category 6 | 1.4 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 21: Category 4 | 3.7 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 14: Category 1.1 | 44.1 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 28: Category 3 | 2.9 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 14: Category 1.2 | 24.3 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 21: Category 1.1 | 45.6 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 14: Category 2 | 0.7 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 28: Category 4 | 2.2 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 14: Category 3 | 6.6 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 21: Category 5 | 8.8 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 14: Category 4 | 7.4 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 14: Category 5 | 10.3 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 14: Category 4 | 5.7 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 14: Category 5 | 15.7 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 14: Category 6 | 8.6 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 21: Category 1.1 | 44.3 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 21: Category 1.2 | 21.4 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 21: Category 2 | 4.3 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 21: Category 3 | 2.9 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 21: Category 4 | 2.9 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 21: Category 5 | 11.4 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 21: Category 6 | 12.9 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 28: Category 1.1 | 47.1 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 28: Category 1.2 | 22.9 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 28: Category 2 | 2.9 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 28: Category 3 | 1.4 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 28: Category 4 | 0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 28: Category 5 | 7.1 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 28: Category 6 | 18.6 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 7: Category 1.1 | 30.0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 7: Category 1.2 | 5.7 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 7: Category 2 | 4.3 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 7: Category 3 | 20.0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 7: Category 4 | 18.6 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 7: Category 5 | 21.4 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 7: Category 6 | 0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 14: Category 1.1 | 42.9 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 14: Category 1.2 | 17.1 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 14: Category 2 | 1.4 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set | Day 14: Category 3 | 8.6 Percentage of Participants |
Secondary
Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set
Percentage of participants with clinical status as assessed by 6-point Ordinal CRS were reported. The 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6) corresponding to below categories, reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: Not hospitalized, not requiring supplemental oxygen (category 1.1); Not hospitalized, requiring supplemental oxygen (category 1.2); Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening.
Time frame: On Day 7, 14, 21, 28
Population: The Primary Analysis Set consisted of all participants in the ITT set with confirmed critical COVID-19 disease defined as score of 4 or 5 on ordinal CRS at baseline. Here 'N' (number of participants analyzed) included all participants evaluable for this outcome measure. Here, 'n' (number analyzed) is defined as participants analyzed for specified categories at specified timepoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 7: Category 3 | 22.5 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 21: Category 1.1 | 23.2 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 14: Category 1.1 | 20.3 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 21: Category 1.2 | 26.1 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 7: Category 1.1 | 7.0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 21: Category 2 | 1.4 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 14: Category 1.2 | 20.3 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 21: Category 3 | 10.1 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 7: Category 4 | 33.8 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 21: Category 4 | 7.2 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 21: Category 5 | 17.4 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 14: Category 2 | 1.4 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 21: Category 6 | 14.5 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 7: Category 2 | 4.2 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 28: Category 1.1 | 29.0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 14: Category 3 | 13.0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 28: Category 1.2 | 27.5 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 7: Category 5 | 25.4 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 28: Category 2 | 0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 14: Category 4 | 13.0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 28: Category 3 | 5.8 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 7: Category 1.2 | 4.2 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 28: Category 4 | 4.3 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 14: Category 5 | 20.3 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 28: Category 5 | 8.7 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 7: Category 6 | 2.8 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 28: Category 6 | 24.6 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 14: Category 6 | 11.6 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 28: Category 6 | 30.0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 7: Category 1.1 | 5.0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 7: Category 1.2 | 2.5 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 7: Category 2 | 0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 7: Category 3 | 25.0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 7: Category 4 | 32.5 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 7: Category 5 | 35.0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 7: Category 6 | 0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 14: Category 1.1 | 17.5 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 14: Category 1.2 | 15.0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 14: Category 2 | 2.5 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 14: Category 3 | 15.0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 14: Category 4 | 10.0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 14: Category 5 | 27.5 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 14: Category 6 | 12.5 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 21: Category 1.1 | 20.0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 21: Category 1.2 | 22.5 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 21: Category 2 | 7.5 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 21: Category 3 | 5.0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 21: Category 5 | 20.0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 21: Category 6 | 20.0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 28: Category 1.1 | 25.0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 28: Category 1.2 | 25.0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 28: Category 2 | 5.0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 28: Category 3 | 2.5 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 28: Category 4 | 0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 28: Category 5 | 12.5 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set | Day 21: Category 4 | 5.0 Percentage of Participants |
Secondary
Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time
Percentage of participants with ECMO over time were reported.
Time frame: From Day 1 up to Day 28
Population: The ITT population restricted to participants who were on ECMO at baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sirukumab + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 11 | 0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 12 | 0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 13 | 0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 1 | 100.0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 2 | 0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 3 | 0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 4 | 0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 5 | 0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 6 | 0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 7 | 0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 8 | 0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 9 | 0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 10 | 0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 14 | 0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 15 | 0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 16 | 0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 17 | 0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 18 | 0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 19 | 0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 20 | 0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 21 | 0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 22 | 0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 23 | 0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 24 | 0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 25 | 0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 26 | 0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 27 | 0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 28 | 0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 25 | 0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 11 | 0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 15 | 0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 12 | 0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 22 | 0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 16 | 0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 1 | 100.0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 27 | 0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 2 | 33.3 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 17 | 0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 3 | 0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 23 | 0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 4 | 0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 18 | 0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 5 | 0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 26 | 0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 6 | 0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 19 | 0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 7 | 0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 24 | 0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 8 | 0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 20 | 0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 9 | 0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 28 | 0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 10 | 0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 13 | 0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 21 | 0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time | Day 14 | 0 Percentage of Participants |
Secondary
Percentage of Participants With Grade 3 and 4 Neutropenia and Lymphocytopenia
Percentage of participants with Grade 3 and 4 neutropenia and lymphocytopenia were reported. The laboratory abnormalities were determined as per division of microbiology and infectious diseases (DMID) adult toxicity as Grade 1: mild (transient or mild discomfort \[less than {\<} 48 hours\]; no medical intervention/therapy required); Grade 2: moderate (mild to moderate limitation in activity - some assistance may be needed; no or minimal medical intervention/therapy required); Grade 3: severe (severe marked limitation in activity, some assistance usually required; medical intervention/therapy required, hospitalizations possible); Grade 4: life-threatening (extreme limitation in activity, significant assistance required; significant medical intervention/therapy required, hospitalization or hospice care probable).
Time frame: Up to Day 28
Population: The All Subjects Treated analysis set consists of all participants who received the study drug. Here, 'N' (Number of participants analyzed) included all participants evaluable for this outcome measure. Here, 'n' (number analyzed) is defined as participants analyzed for specified categories.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sirukumab + SOC | Percentage of Participants With Grade 3 and 4 Neutropenia and Lymphocytopenia | Neutropenia: Grade 3 | 0 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Grade 3 and 4 Neutropenia and Lymphocytopenia | Lymphocytopenia: Grade 3 | 6.6 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Grade 3 and 4 Neutropenia and Lymphocytopenia | Neutropenia: Grade 4 | 0.7 Percentage of Participants |
| Sirukumab + SOC | Percentage of Participants With Grade 3 and 4 Neutropenia and Lymphocytopenia | Lymphocytopenia: Grade 4 | 6.6 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Grade 3 and 4 Neutropenia and Lymphocytopenia | Neutropenia: Grade 4 | 0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Grade 3 and 4 Neutropenia and Lymphocytopenia | Neutropenia: Grade 3 | 0 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Grade 3 and 4 Neutropenia and Lymphocytopenia | Lymphocytopenia: Grade 4 | 10.1 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Grade 3 and 4 Neutropenia and Lymphocytopenia | Lymphocytopenia: Grade 3 | 7.2 Percentage of Participants |
Secondary
Percentage of Participants With Increased Alanine Transaminase (ALT) Greater Than or Equal to (>=)3*Upper Limit Normal (ULN) Combined With Increased Bilirubin Greater Than (>)2*ULN
Percentage of participants with increased ALT \>=3\*ULN combined with increased bilirubin \>2\*ULN were reported.
Time frame: Up to Day 28
Population: The All Subjects Treated analysis set consists of all participants who received the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sirukumab + SOC | Percentage of Participants With Increased Alanine Transaminase (ALT) Greater Than or Equal to (>=)3*Upper Limit Normal (ULN) Combined With Increased Bilirubin Greater Than (>)2*ULN | 2.2 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Increased Alanine Transaminase (ALT) Greater Than or Equal to (>=)3*Upper Limit Normal (ULN) Combined With Increased Bilirubin Greater Than (>)2*ULN | 1.4 Percentage of Participants |
Secondary
Percentage of Participants With Related Adverse Events (AEs)
Percentage of participants with related AEs were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
Time frame: Up to Day 28
Population: The All Subjects Treated analysis set consisted of all participants who received the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sirukumab + SOC | Percentage of Participants With Related Adverse Events (AEs) | 11.5 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Related Adverse Events (AEs) | 7.1 Percentage of Participants |
Secondary
Percentage of Participants With SAEs (Follow-up Phase)
Percentage of participants with SAEs were reported. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
Time frame: From Week 4 up to Week 16
Population: The All Subjects Treated analysis set consists of all participants who received the study drug. Here, 'N' (Number of participants analyzed) included all participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sirukumab + SOC | Percentage of Participants With SAEs (Follow-up Phase) | 5.9 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With SAEs (Follow-up Phase) | 5.3 Percentage of Participants |
Secondary
Percentage of Participants With Serious Adverse Events (SAEs) (Treatment Phase)
Percentage of participants with SAEs were reported. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
Time frame: Up to Day 28
Population: The All Subjects treated analysis set consisted of all participants who received the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sirukumab + SOC | Percentage of Participants With Serious Adverse Events (SAEs) (Treatment Phase) | 25.2 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Serious Adverse Events (SAEs) (Treatment Phase) | 31.4 Percentage of Participants |
Secondary
Percentage of Participants With Severe or Life-threatening, Bacterial, Invasive Fungal, Viral or Opportunistic Infections
Percentage of participants with severe or Life-threatening, bacterial, invasive fungal, viral or opportunistic infections were reported.
Time frame: Up to Day 28
Population: The All Subjects treated analysis set consisted of all participants who received the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sirukumab + SOC | Percentage of Participants With Severe or Life-threatening, Bacterial, Invasive Fungal, Viral or Opportunistic Infections | 11.5 Percentage of Participants |
| Placebo + SOC | Percentage of Participants With Severe or Life-threatening, Bacterial, Invasive Fungal, Viral or Opportunistic Infections | 11.4 Percentage of Participants |
Secondary
Time From Study Intervention Administration to End of Oxygen Supplementation
Time from study intervention administration to end of oxygen supplementation was reported.
Time frame: Up to Day 28
Population: The ITT analysis set consisted of all participants who were randomized and treated in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sirukumab + SOC | Time From Study Intervention Administration to End of Oxygen Supplementation | 24.0 Days |
| Placebo + SOC | Time From Study Intervention Administration to End of Oxygen Supplementation | 20.00 Days |
Secondary
Time From Study Intervention Administration to Hospital Discharge Among the Surviving Participants
Time from study intervention administration to hospital discharge among the surviving participants was reported.
Time frame: Up to Day 28
Population: The ITT population restricted to participants surviving up to Day 28.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sirukumab + SOC | Time From Study Intervention Administration to Hospital Discharge Among the Surviving Participants | 8.00 Days |
| Placebo + SOC | Time From Study Intervention Administration to Hospital Discharge Among the Surviving Participants | 9.00 Days |
Secondary
Time to Sustained Improvement of at Least 1 Category on 6-point Ordinal CRS: ITT Set
Time to sustained improvement is defined as an improvement of at least 1 category relative to baseline on the 6-point ordinal clinical recovery scale, sustained until Day 28. The 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6) corresponding to below categories, reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: not hospitalized, including participants on low level of oxygen (category 1); Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening.
Time frame: Up to Day 28
Population: The ITT analysis set consisted of all participants who were randomized and treated in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sirukumab + SOC | Time to Sustained Improvement of at Least 1 Category on 6-point Ordinal CRS: ITT Set | 7.00 Days |
| Placebo + SOC | Time to Sustained Improvement of at Least 1 Category on 6-point Ordinal CRS: ITT Set | 7.00 Days |
Secondary
Time to Sustained Improvement of at Least 1 Category on 6-point Ordinal CRS: Primary Analysis Set
Time to sustained improvement is defined as an improvement of at least 1 category relative to baseline on the 6-point ordinal clinical recovery scale, sustained until Day 28. The 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6) corresponding to below categories, reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: not hospitalized, including participants on low level of oxygen (category 1); Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening.
Time frame: Up to Day 28
Population: The Primary Analysis Set consisted of all participants in the ITT analysis set with confirmed critical COVID-19 disease defined as score of 4 or 5 on the ordinal CRS at baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sirukumab + SOC | Time to Sustained Improvement of at Least 1 Category on 6-point Ordinal CRS: Primary Analysis Set | 9.00 Days |
| Placebo + SOC | Time to Sustained Improvement of at Least 1 Category on 6-point Ordinal CRS: Primary Analysis Set | 15.50 Days |
Secondary
Time to Sustained Improvement of at Least 2 Categories on 6-point Ordinal CRS: Intent-to-Treat (ITT) Set
Time to sustained improvement is defined as an improvement of at least 2 categories relative to baseline on the 6-point ordinal clinical recovery scale, sustained until Day 28. The 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6) corresponding to below categories, reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: not hospitalized, including participants on low level of oxygen (category 1); Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening.
Time frame: Up to Day 28
Population: The ITT analysis set consisted of all participants who were randomized and treated in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sirukumab + SOC | Time to Sustained Improvement of at Least 2 Categories on 6-point Ordinal CRS: Intent-to-Treat (ITT) Set | 9.00 Days |
| Placebo + SOC | Time to Sustained Improvement of at Least 2 Categories on 6-point Ordinal CRS: Intent-to-Treat (ITT) Set | 10.00 Days |
Secondary
Total Length of Hospitalization Among the Surviving Participants
Total length of hospitalization, defined as total duration of hospital stay, among the surviving participants was reported.
Time frame: Up to Day 28
Population: The ITT population restricted to participants surviving up to Day 28.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sirukumab + SOC | Total Length of Hospitalization Among the Surviving Participants | 10.42 Days | Standard Deviation 8.274 |
| Placebo + SOC | Total Length of Hospitalization Among the Surviving Participants | 11.19 Days | Standard Deviation 8.37 |
Secondary
Total Time on ECMO
Total time for participants on ECMO was reported.
Time frame: Up to Day 28
Population: The ITT set restricted to participants who were on ECMO at baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sirukumab + SOC | Total Time on ECMO | 1.0 Days | Standard Deviation 0 |
| Placebo + SOC | Total Time on ECMO | 1.3 Days | Standard Deviation 0.58 |
Secondary
Total Time on Invasive Mechanical Ventilation
Total time on invasive mechanical ventilation in participants who were on invasive mechanical ventilation at baseline was reported.
Time frame: Up to Day 28
Population: The Primary Analysis Set restricted to participants who were on invasive mechanical ventilation at baseline. Here 'N' (number of participants analyzed) included all participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sirukumab + SOC | Total Time on Invasive Mechanical Ventilation | 14.18 Days | Standard Deviation 11.062 |
| Placebo + SOC | Total Time on Invasive Mechanical Ventilation | 21.37 Days | Standard Deviation 9.546 |