COVID-19 Pneumonia
Conditions
Brief summary
This study will evaluate the efficacy, safety, pharmacodynamics, and pharmacokinetics of tocilizumab (TCZ) compared with a matching placebo in combination with standard of care (SOC) in hospitalized patients with severe COVID-19 pneumonia.
Interventions
Participants will receive 1 dose of IV TCZ. 1 additional dose may be given if clinical symptoms worsen or show no improvement.
DRUGPlacebo
Participants will receive 1 dose of IV placebo matched to TCZ. Up to 1 additional dose may be given if clinical symptoms worsen or show no improvement.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Hospitalized with COVID-19 pneumonia confirmed per WHO criteria (including a positive PCR of any specimen; e.g., respiratory, blood, urine, stool, other bodily fluid) and evidenced by chest X-ray or CT scan * SPO2 \</=93% or PaO2/FiO2 \<300 mmHg
Exclusion criteria
* Known severe allergic reactions to TCZ or other monoclonal antibodies * Active tuberculosis (TB) infection * Suspected active bacterial, fungal, viral, or other infection (besides COVID-19) * In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments * Have received oral anti-rejection or immunomodulatory drugs (including TCZ) with the past 3 months * Participating in other drug clinical trials (participation in COVID-19 anti-viral trials may be permitted if approved by Medical Monitor) * Pregnant or breastfeeding, or positive pregnancy test in a pre-dose examination * Treatment with an investigational drug within 5 half-lives or 30 days (whichever is longer) of randomization (investigational COVID-19 antivirals may be permitted if approved by Medial Monitor) * Any serious medical condition or abnormality of clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 10 x upper limit of normal (ULN) detected within 24 hours at screening (per local lab) * Absolute neutrophil count (ANC) \< 1000/mL at screening (per local lab) * Platelet count \< 50,000/mL at screening (per local lab)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 28 (Week 4) | Day 28 | Clinical status was assessed using a 7-category ordinal scale: 1. \- Discharged (or ready for discharge) 2. \- Non- intensive care unit (ICU) hospital ward (or ready for hospital ward) not requiring supplemental oxygen 3. \- Non-ICU hospital ward (or ready for hospital ward) requiring supplemental oxygen 4. \- ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen 5. \- ICU, requiring intubation and mechanical ventilation 6. \- ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support 7. \- Death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status | Up to Day 28 | Time to improvement for this outcome measure was defined as the days from the first dose of study drug to when at least a 2-category improvement in clinical status (based on a 7-category ordinal scale) is observed. Participants who died were censored at Day 28. |
| Time to Hospital Discharge or Ready for Discharge | Up to Day 28 | Time to Hospital Discharge was defined as the time from the first dose of study drug to hospital discharge or ready for discharge (normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or \</=2L supplemental oxygen) Participants who died were censored at Day 28. |
| Incidence of Mechanical Ventilation by Day 28 | Up to Day 28 | Participants who died by Day 28 were assumed to have required mechanical ventilation. |
| Ventilator-Free Days to Day 28 | Up to Day 28 | Participants who died by Day 28 were assigned 0 ventilator-free days. |
| Incidence of Intensive Care Unit (ICU) Stay by Day 28 (Week 4) | Up to Day 28 | Participants who died by Day 28 were assumed to have required an ICU stay. |
| Time to Clinical Improvement (TTCI), Defined as a National Early Warning Score 2 (NEWS2) of </= 2 Maintained for 24 Hours | Up to Day 28 | Defined as time from first dose of study drug to at least two NEWS2 assessments with a score of \<=2 covering a span of at least 21.5 hours, with a maximum of 26.5 hours between the first and last of these assessments and no assessments with a score \>2 in between. If one of the components of the NEWS2 score was missing at a particular time point, then the NEWS2 score was not calculated. Participants who died were censored at Day 28. |
| Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 14 | Day 14 | Clinical status was assessed using a 7-category ordinal scale: 1. \- Discharged (or ready for discharge) 2. \- Non- intensive care unit (ICU) hospital ward (or ready for hospital ward) not requiring supplemental oxygen 3. \- Non-ICU hospital ward (or ready for hospital ward) requiring supplemental oxygen 4. \- ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen 5. \- ICU, requiring intubation and mechanical ventilation 6. \- ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support 7. \- Death |
| Time to Clinical Failure to Day 28 (Week 4) | Up to Day 28 | Time to clinical failure was defined as the number of days from the first dose of study drug to the first occurrence on study of death, mechanical ventilation, ICU admission, or study withdrawal prior to discharge, whichever occurs first. |
| Mortality Rate at Day 28 (Week 4) | Day 28 | — |
| Time to Recovery to Day 28 (Week 4) | Up to Day 28 | Time to recovery was defined as the number of days from the first dose of study drug to hospital discharge or ready for discharge (normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen) or non-ICU hospital ward or ready for hospital ward not requiring supplemental oxygen. Participants who died were censored at Day 28. |
| Duration of Supplemental Oxygen to Day 28 (Week 4) | Up to Day 28 | Participants who died by Day 28 were assigned a duration of 28 days of supplemental oxygen. |
| Duration of ICU Stay to Day 28 (Week 4) | Up to Day 28 | Participants who died by Day 28 were assigned a duration from the first dose of study drug to Day 28 at hour 23:59:59. |
Countries
Canada, Denmark, France, Germany, Italy, Netherlands, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
452 participants were randomized in the study. Of the 452 participants enrolled, 14 were randomized but not dosed and therefore discontinued from the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Modified Intent-to-Treat (mITT) Arm Participants randomized to the placebo arm who received any amount of study drug. Participants randomized to the placebo arm were to receive 1 IV infusion of placebo matched to TCZ. Up to 1 additional dose could be given if clinical symptoms worsened or showed no improvement. | 144 |
| Tocilizumab (TCZ) mITT Arm Participants randomized to the TCZ arm who received any amount of study drug. Participants randomized to the TCZ arm were to receive 1 intravenous (IV) infusion of TCZ, dosed at 8 mg/kg, up to a maximum dose 800 mg. Up to 1 additional dose could be given if clinical symptoms worsened or showed no improvement. | 294 |
| Total | 438 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 35 | 71 |
| Overall Study | Lost to Follow-up | 5 | 23 |
| Overall Study | Other | 2 | 0 |
| Overall Study | Physician Decision | 2 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 10 |
Baseline characteristics
| Characteristic | Tocilizumab (TCZ) mITT Arm | Total | Placebo Modified Intent-to-Treat (mITT) Arm |
|---|---|---|---|
| Age, Continuous | 60.9 Years STANDARD_DEVIATION 14.6 | 60.8 Years STANDARD_DEVIATION 14.3 | 60.6 Years STANDARD_DEVIATION 13.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 94 Participants | 141 Participants | 47 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 181 Participants | 267 Participants | 86 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 19 Participants | 30 Participants | 11 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 8 Participants | 13 Participants | 5 Participants |
| Race (NIH/OMB) Asian | 28 Participants | 38 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 40 Participants | 66 Participants | 26 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 3 Participants | 8 Participants | 5 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 39 Participants | 60 Participants | 21 Participants |
| Race (NIH/OMB) White | 176 Participants | 252 Participants | 76 Participants |
| Sex: Female, Male Female | 89 Participants | 132 Participants | 43 Participants |
| Sex: Female, Male Male | 205 Participants | 306 Participants | 101 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 36 / 143 | 72 / 295 |
| other Total, other adverse events | 29 / 143 | 83 / 295 |
| serious Total, serious adverse events | 64 / 143 | 116 / 295 |
Outcome results
Primary
Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 28 (Week 4)
Clinical status was assessed using a 7-category ordinal scale: 1. \- Discharged (or ready for discharge) 2. \- Non- intensive care unit (ICU) hospital ward (or ready for hospital ward) not requiring supplemental oxygen 3. \- Non-ICU hospital ward (or ready for hospital ward) requiring supplemental oxygen 4. \- ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen 5. \- ICU, requiring intubation and mechanical ventilation 6. \- ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support 7. \- Death
Time frame: Day 28
Population: mITT population: Defined as all randomized participants who received any amount of study medication, with participants grouped according to the treatment assigned at randomization.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab (TCZ) mITT Arm | Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 28 (Week 4) | 3 | 4.8 Percentage of Participants |
| Tocilizumab (TCZ) mITT Arm | Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 28 (Week 4) | 5 | 8.8 Percentage of Participants |
| Tocilizumab (TCZ) mITT Arm | Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 28 (Week 4) | 2 | 2.0 Percentage of Participants |
| Tocilizumab (TCZ) mITT Arm | Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 28 (Week 4) | 6 | 6.1 Percentage of Participants |
| Tocilizumab (TCZ) mITT Arm | Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 28 (Week 4) | 4 | 2.0 Percentage of Participants |
| Tocilizumab (TCZ) mITT Arm | Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 28 (Week 4) | 7 | 19.7 Percentage of Participants |
| Tocilizumab (TCZ) mITT Arm | Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 28 (Week 4) | 1 | 56.5 Percentage of Participants |
| Placebo Modified Intent-to-Treat (mITT) Arm | Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 28 (Week 4) | 7 | 19.4 Percentage of Participants |
| Placebo Modified Intent-to-Treat (mITT) Arm | Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 28 (Week 4) | 1 | 49.3 Percentage of Participants |
| Placebo Modified Intent-to-Treat (mITT) Arm | Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 28 (Week 4) | 2 | 5.6 Percentage of Participants |
| Placebo Modified Intent-to-Treat (mITT) Arm | Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 28 (Week 4) | 3 | 2.8 Percentage of Participants |
| Placebo Modified Intent-to-Treat (mITT) Arm | Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 28 (Week 4) | 4 | 6.9 Percentage of Participants |
| Placebo Modified Intent-to-Treat (mITT) Arm | Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 28 (Week 4) | 5 | 9.7 Percentage of Participants |
| Placebo Modified Intent-to-Treat (mITT) Arm | Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 28 (Week 4) | 6 | 6.3 Percentage of Participants |
p-value: 0.3695% CI: [-2.5, 0]Van Elteren Test
Secondary
Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 14
Clinical status was assessed using a 7-category ordinal scale: 1. \- Discharged (or ready for discharge) 2. \- Non- intensive care unit (ICU) hospital ward (or ready for hospital ward) not requiring supplemental oxygen 3. \- Non-ICU hospital ward (or ready for hospital ward) requiring supplemental oxygen 4. \- ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen 5. \- ICU, requiring intubation and mechanical ventilation 6. \- ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support 7. \- Death
Time frame: Day 14
Population: mITT population: Defined as all randomized participants who received any amount of study medication, with participants grouped according to the treatment assigned at randomization.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab (TCZ) mITT Arm | Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 14 | 3 | 6.5 Percentage of participants |
| Tocilizumab (TCZ) mITT Arm | Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 14 | 5 | 14.6 Percentage of participants |
| Tocilizumab (TCZ) mITT Arm | Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 14 | 2 | 6.1 Percentage of participants |
| Tocilizumab (TCZ) mITT Arm | Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 14 | 6 | 12.6 Percentage of participants |
| Tocilizumab (TCZ) mITT Arm | Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 14 | 4 | 7.1 Percentage of participants |
| Tocilizumab (TCZ) mITT Arm | Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 14 | 7 | 13.3 Percentage of participants |
| Tocilizumab (TCZ) mITT Arm | Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 14 | 1 | 39.8 Percentage of participants |
| Placebo Modified Intent-to-Treat (mITT) Arm | Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 14 | 7 | 13.2 Percentage of participants |
| Placebo Modified Intent-to-Treat (mITT) Arm | Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 14 | 1 | 29.9 Percentage of participants |
| Placebo Modified Intent-to-Treat (mITT) Arm | Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 14 | 2 | 4.9 Percentage of participants |
| Placebo Modified Intent-to-Treat (mITT) Arm | Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 14 | 3 | 11.1 Percentage of participants |
| Placebo Modified Intent-to-Treat (mITT) Arm | Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 14 | 4 | 7.6 Percentage of participants |
| Placebo Modified Intent-to-Treat (mITT) Arm | Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 14 | 5 | 16.0 Percentage of participants |
| Placebo Modified Intent-to-Treat (mITT) Arm | Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 14 | 6 | 17.4 Percentage of participants |
p-value: 0.054895% CI: [-2, 0.5]Van Elteren test
Secondary
Duration of ICU Stay to Day 28 (Week 4)
Participants who died by Day 28 were assigned a duration from the first dose of study drug to Day 28 at hour 23:59:59.
Time frame: Up to Day 28
Population: mITT population: Defined as all randomized participants who received any amount of study medication, with participants grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tocilizumab (TCZ) mITT Arm | Duration of ICU Stay to Day 28 (Week 4) | 9.8 Days |
| Placebo Modified Intent-to-Treat (mITT) Arm | Duration of ICU Stay to Day 28 (Week 4) | 15.5 Days |
p-value: 0.045495% CI: [-15, 2.9]Van Elteren test
Secondary
Duration of Supplemental Oxygen to Day 28 (Week 4)
Participants who died by Day 28 were assigned a duration of 28 days of supplemental oxygen.
Time frame: Up to Day 28
Population: mITT population: Defined as all randomized participants who received any amount of study medication, with participants grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tocilizumab (TCZ) mITT Arm | Duration of Supplemental Oxygen to Day 28 (Week 4) | 26.5 Days |
| Placebo Modified Intent-to-Treat (mITT) Arm | Duration of Supplemental Oxygen to Day 28 (Week 4) | 28.0 Days |
p-value: 0.047795% CI: [-9, 0.5]Van Elteren test
Secondary
Incidence of Intensive Care Unit (ICU) Stay by Day 28 (Week 4)
Participants who died by Day 28 were assumed to have required an ICU stay.
Time frame: Up to Day 28
Population: mITT population: Defined as all randomized participants who received any amount of study medication, with participants grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab (TCZ) mITT Arm | Incidence of Intensive Care Unit (ICU) Stay by Day 28 (Week 4) | 66.0 Percentage of Participants |
| Placebo Modified Intent-to-Treat (mITT) Arm | Incidence of Intensive Care Unit (ICU) Stay by Day 28 (Week 4) | 71.5 Percentage of Participants |
| TCZ - No Mechanical Ventilation at Baseline | Incidence of Intensive Care Unit (ICU) Stay by Day 28 (Week 4) | 21.3 Percentage of Participants |
| Placebo - No Mechanical Ventilation at Baseline | Incidence of Intensive Care Unit (ICU) Stay by Day 28 (Week 4) | 35.9 Percentage of Participants |
p-value: 0.151495% CI: [-13.7, 2.2]Cochran-Mantel-Haenszel
p-value: 0.02995% CI: [-28.6, -1]Cochran-Mantel-Haenszel
Secondary
Incidence of Mechanical Ventilation by Day 28
Participants who died by Day 28 were assumed to have required mechanical ventilation.
Time frame: Up to Day 28
Population: mITT population: Defined as all randomized participants who received any amount of study medication, with participants grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab (TCZ) mITT Arm | Incidence of Mechanical Ventilation by Day 28 | 54.4 Percentage of Participants |
| Placebo Modified Intent-to-Treat (mITT) Arm | Incidence of Mechanical Ventilation by Day 28 | 60.4 Percentage of Participants |
| TCZ - No Mechanical Ventilation at Baseline | Incidence of Mechanical Ventilation by Day 28 | 27.9 Percentage of Participants |
| Placebo - No Mechanical Ventilation at Baseline | Incidence of Mechanical Ventilation by Day 28 | 36.7 Percentage of Participants |
p-value: 0.099695% CI: [-13.8, 1.4]Cochran-Mantel-Haenszel
p-value: 0.135595% CI: [-20.7, 3]Cochran-Mantel-Haenszel
Secondary
Mortality Rate at Day 28 (Week 4)
Time frame: Day 28
Population: mITT population: Defined as all randomized participants who received any amount of study medication, with participants grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab (TCZ) mITT Arm | Mortality Rate at Day 28 (Week 4) | 19.7 Percentage of Participants |
| Placebo Modified Intent-to-Treat (mITT) Arm | Mortality Rate at Day 28 (Week 4) | 19.4 Percentage of Participants |
p-value: 0.94195% CI: [-7.6, 8.2]Cochran-Mantel-Haenszel
Secondary
Time to Clinical Failure to Day 28 (Week 4)
Time to clinical failure was defined as the number of days from the first dose of study drug to the first occurrence on study of death, mechanical ventilation, ICU admission, or study withdrawal prior to discharge, whichever occurs first.
Time frame: Up to Day 28
Population: mITT population: Defined as all randomized participants who received any amount of study medication, with participants grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tocilizumab (TCZ) mITT Arm | Time to Clinical Failure to Day 28 (Week 4) | NA Days |
| Placebo Modified Intent-to-Treat (mITT) Arm | Time to Clinical Failure to Day 28 (Week 4) | NA Days |
p-value: 0.162795% CI: [0.57, 1.1]Log Rank
Secondary
Time to Clinical Improvement (TTCI), Defined as a National Early Warning Score 2 (NEWS2) of </= 2 Maintained for 24 Hours
Defined as time from first dose of study drug to at least two NEWS2 assessments with a score of \<=2 covering a span of at least 21.5 hours, with a maximum of 26.5 hours between the first and last of these assessments and no assessments with a score \>2 in between. If one of the components of the NEWS2 score was missing at a particular time point, then the NEWS2 score was not calculated. Participants who died were censored at Day 28.
Time frame: Up to Day 28
Population: mITT population: Defined as all randomized participants who received any amount of study medication, with participants grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tocilizumab (TCZ) mITT Arm | Time to Clinical Improvement (TTCI), Defined as a National Early Warning Score 2 (NEWS2) of </= 2 Maintained for 24 Hours | NA Days |
| Placebo Modified Intent-to-Treat (mITT) Arm | Time to Clinical Improvement (TTCI), Defined as a National Early Warning Score 2 (NEWS2) of </= 2 Maintained for 24 Hours | NA Days |
p-value: 0.044395% CI: [1.01, 2.08]Log Rank
Secondary
Time to Hospital Discharge or Ready for Discharge
Time to Hospital Discharge was defined as the time from the first dose of study drug to hospital discharge or ready for discharge (normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or \</=2L supplemental oxygen) Participants who died were censored at Day 28.
Time frame: Up to Day 28
Population: mITT population: Defined as all randomized participants who received any amount of study medication, with participants grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tocilizumab (TCZ) mITT Arm | Time to Hospital Discharge or Ready for Discharge | 20.0 Days |
| Placebo Modified Intent-to-Treat (mITT) Arm | Time to Hospital Discharge or Ready for Discharge | 28.0 Days |
p-value: 0.03795% CI: [1.02, 1.79]Log Rank
Secondary
Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status
Time to improvement for this outcome measure was defined as the days from the first dose of study drug to when at least a 2-category improvement in clinical status (based on a 7-category ordinal scale) is observed. Participants who died were censored at Day 28.
Time frame: Up to Day 28
Population: mITT population: Defined as all randomized participants who received any amount of study medication, with participants grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tocilizumab (TCZ) mITT Arm | Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status | 14.0 Days |
| Placebo Modified Intent-to-Treat (mITT) Arm | Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status | 18.0 Days |
p-value: 0.08295% CI: [0.97, 1.64]Log Rank
Secondary
Time to Recovery to Day 28 (Week 4)
Time to recovery was defined as the number of days from the first dose of study drug to hospital discharge or ready for discharge (normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen) or non-ICU hospital ward or ready for hospital ward not requiring supplemental oxygen. Participants who died were censored at Day 28.
Time frame: Up to Day 28
Population: mITT population: Defined as all randomized participants who received any amount of study medication, with participants grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tocilizumab (TCZ) mITT Arm | Time to Recovery to Day 28 (Week 4) | 16.0 Days |
| Placebo Modified Intent-to-Treat (mITT) Arm | Time to Recovery to Day 28 (Week 4) | 24.0 Days |
p-value: 0.052895% CI: [1, 1.72]Log Rank
Secondary
Ventilator-Free Days to Day 28
Participants who died by Day 28 were assigned 0 ventilator-free days.
Time frame: Up to Day 28
Population: mITT population: Defined as all randomized participants who received any amount of study medication, with participants grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tocilizumab (TCZ) mITT Arm | Ventilator-Free Days to Day 28 | 22.0 Days |
| Placebo Modified Intent-to-Treat (mITT) Arm | Ventilator-Free Days to Day 28 | 16.5 Days |
p-value: 0.320295% CI: [-2.8, 13]Van Elteren test