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A Study to Evaluate the Safety and Efficacy of Tocilizumab in Patients With Severe COVID-19 Pneumonia (COVACTA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04320615
Recruitment Status : Completed
First Posted : March 25, 2020
Results First Posted : June 30, 2021
Last Update Posted : June 30, 2021
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition COVID-19 Pneumonia
Interventions Drug: Tocilizumab (TCZ)
Drug: Placebo
Enrollment 452
Recruitment Details  
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.
Arm/Group Title Placebo Modified Intent-to-Treat (mITT) Arm Tocilizumab (TCZ) mITT Arm
Hide Arm/Group Description 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. 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.
Period Title: Overall Study
Started 144 294
Completed 96 190
Not Completed 48 104
Reason Not Completed
Withdrawal by Subject             4             10
Physician Decision             2             0
Other             2             0
Lost to Follow-up             5             23
Death             35             71
Arm/Group Title Placebo Modified Intent-to-Treat (mITT) Arm Tocilizumab (TCZ) mITT Arm Total
Hide Arm/Group Description 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. 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. Total of all reporting groups
Overall Number of Baseline Participants 144 294 438
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 144 participants 294 participants 438 participants
60.6  (13.7) 60.9  (14.6) 60.8  (14.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 144 participants 294 participants 438 participants
Female
43
  29.9%
89
  30.3%
132
  30.1%
Male
101
  70.1%
205
  69.7%
306
  69.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 144 participants 294 participants 438 participants
Hispanic or Latino
47
  32.6%
94
  32.0%
141
  32.2%
Not Hispanic or Latino
86
  59.7%
181
  61.6%
267
  61.0%
Unknown or Not Reported
11
   7.6%
19
   6.5%
30
   6.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 144 participants 294 participants 438 participants
American Indian or Alaska Native
5
   3.5%
8
   2.7%
13
   3.0%
Asian
10
   6.9%
28
   9.5%
38
   8.7%
Native Hawaiian or Other Pacific Islander
5
   3.5%
3
   1.0%
8
   1.8%
Black or African American
26
  18.1%
40
  13.6%
66
  15.1%
White
76
  52.8%
176
  59.9%
252
  57.5%
More than one race
1
   0.7%
0
   0.0%
1
   0.2%
Unknown or Not Reported
21
  14.6%
39
  13.3%
60
  13.7%
1.Primary Outcome
Title Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 28 (Week 4)
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Tocilizumab (TCZ) mITT Arm Placebo Modified Intent-to-Treat (mITT) Arm
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 294 144
Measure Type: Number
Unit of Measure: Percentage of Participants
1 56.5 49.3
2 2.0 5.6
3 4.8 2.8
4 2.0 6.9
5 8.8 9.7
6 6.1 6.3
7 19.7 19.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) mITT Arm, Placebo Modified Intent-to-Treat (mITT) Arm
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3600
Comments [Not Specified]
Method Van Elteren Test
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-2.5 to 0.0
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Time to Clinical Improvement (TTCI), Defined as a National Early Warning Score 2 (NEWS2) of </= 2 Maintained for 24 Hours
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Tocilizumab (TCZ) mITT Arm Placebo Modified Intent-to-Treat (mITT) Arm
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 294 144
Median (95% Confidence Interval)
Unit of Measure: Days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
NA = Value not estimable (NE) due to an insufficient number of events.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) mITT Arm, Placebo Modified Intent-to-Treat (mITT) Arm
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0443
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.448
Confidence Interval (2-Sided) 95%
1.01 to 2.08
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Tocilizumab (TCZ) mITT Arm Placebo Modified Intent-to-Treat (mITT) Arm
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 294 144
Median (95% Confidence Interval)
Unit of Measure: Days
14.0
(12.0 to 17.0)
18.0
(15.0 to 28.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) mITT Arm, Placebo Modified Intent-to-Treat (mITT) Arm
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0820
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.263
Confidence Interval (2-Sided) 95%
0.97 to 1.64
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Time to Hospital Discharge or "Ready for Discharge"
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Tocilizumab (TCZ) mITT Arm Placebo Modified Intent-to-Treat (mITT) Arm
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 294 144
Median (95% Confidence Interval)
Unit of Measure: Days
20.0
(17.0 to 27.0)
28.0 [1] 
(20.0 to NA)
[1]
NA = Value not estimable (NE) due to an insufficient number of events.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) mITT Arm, Placebo Modified Intent-to-Treat (mITT) Arm
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0370
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.350
Confidence Interval (2-Sided) 95%
1.02 to 1.79
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Incidence of Mechanical Ventilation by Day 28
Hide Description Participants who died by Day 28 were assumed to have required mechanical ventilation.
Time Frame Up to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Tocilizumab (TCZ) mITT Arm Placebo Modified Intent-to-Treat (mITT) Arm TCZ - No Mechanical Ventilation at Baseline Placebo - No Mechanical Ventilation at Baseline
Hide Arm/Group Description:
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.
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.
Participants randomized to the TCZ arm who received any amount of study drug and were not on mechanical ventilation at baseline. 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.
Participants randomized to the placebo arm who received any amount of study drug and were not on mechanical ventilation at baseline. 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.
Overall Number of Participants Analyzed 294 144 183 90
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
54.4
(48.7 to 60.1)
60.4
(52.4 to 68.4)
27.9
(21.4 to 34.4)
36.7
(26.7 to 46.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) mITT Arm, Placebo Modified Intent-to-Treat (mITT) Arm
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0996
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Weighted % difference
Estimated Value -6.2
Confidence Interval (2-Sided) 95%
-13.8 to 1.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection TCZ - No Mechanical Ventilation at Baseline, Placebo - No Mechanical Ventilation at Baseline
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1355
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Weighted % difference
Estimated Value -8.9
Confidence Interval (2-Sided) 95%
-20.7 to 3.0
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Ventilator-Free Days to Day 28
Hide Description Participants who died by Day 28 were assigned 0 ventilator-free days.
Time Frame Up to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Tocilizumab (TCZ) mITT Arm Placebo Modified Intent-to-Treat (mITT) Arm
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 294 144
Median (95% Confidence Interval)
Unit of Measure: Days
22.0
(18.0 to 28.0)
16.5
(11.0 to 26.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) mITT Arm, Placebo Modified Intent-to-Treat (mITT) Arm
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3202
Comments [Not Specified]
Method Van Elteren test
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 5.5
Confidence Interval (2-Sided) 95%
-2.8 to 13.0
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Incidence of Intensive Care Unit (ICU) Stay by Day 28 (Week 4)
Hide Description Participants who died by Day 28 were assumed to have required an ICU stay.
Time Frame Up to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Tocilizumab (TCZ) mITT Arm Placebo Modified Intent-to-Treat (mITT) Arm TCZ - Not in ICU at Baseline Placebo - Not in ICU at Baseline
Hide Arm/Group Description:
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.
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.
Participants randomized to the TCZ arm who received any amount of study drug and were not in the ICU at baseline. 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.
Participants randomized to the placebo arm who received any amount of study drug and were not in the ICU at baseline. 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.
Overall Number of Participants Analyzed 294 144 127 64
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
66.0
(60.6 to 71.4)
71.5
(64.2 to 78.9)
21.3
(14.1 to 28.4)
35.9
(24.2 to 47.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) mITT Arm, Placebo Modified Intent-to-Treat (mITT) Arm
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1514
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Weighted % difference
Estimated Value -5.7
Confidence Interval (2-Sided) 95%
-13.7 to 2.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection TCZ - Not in ICU at Baseline, Placebo - Not in ICU at Baseline
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0290
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Weighted % difference
Estimated Value -14.8
Confidence Interval (2-Sided) 95%
-28.6 to -1.0
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Duration of ICU Stay to Day 28 (Week 4)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Tocilizumab (TCZ) mITT Arm Placebo Modified Intent-to-Treat (mITT) Arm
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 294 144
Median (95% Confidence Interval)
Unit of Measure: Days
9.8
(7.0 to 15.7)
15.5
(8.7 to 25.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) mITT Arm, Placebo Modified Intent-to-Treat (mITT) Arm
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0454
Comments [Not Specified]
Method Van Elteren test
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -5.8
Confidence Interval (2-Sided) 95%
-15.0 to 2.9
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 14
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Tocilizumab (TCZ) mITT Arm Placebo Modified Intent-to-Treat (mITT) Arm
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 294 144
Measure Type: Number
Unit of Measure: Percentage of participants
1 39.8 29.9
2 6.1 4.9
3 6.5 11.1
4 7.1 7.6
5 14.6 16.0
6 12.6 17.4
7 13.3 13.2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) mITT Arm, Placebo Modified Intent-to-Treat (mITT) Arm
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0548
Comments [Not Specified]
Method Van Elteren test
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-2.0 to 0.5
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Time to Clinical Failure to Day 28 (Week 4)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Tocilizumab (TCZ) mITT Arm Placebo Modified Intent-to-Treat (mITT) Arm
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 294 144
Median (95% Confidence Interval)
Unit of Measure: Days
NA [1] 
(NA to NA)
NA [1] 
(21.0 to NA)
[1]
NA = Value not estimable (NE) due to an insufficient number of events.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) mITT Arm, Placebo Modified Intent-to-Treat (mITT) Arm
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1627
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.790
Confidence Interval (2-Sided) 95%
0.57 to 1.10
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Mortality Rate at Day 28 (Week 4)
Hide Description [Not Specified]
Time Frame Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Tocilizumab (TCZ) mITT Arm Placebo Modified Intent-to-Treat (mITT) Arm
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 294 144
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
19.7
(15.2 to 24.3)
19.4
(13.0 to 25.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) mITT Arm, Placebo Modified Intent-to-Treat (mITT) Arm
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9410
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Weighted % difference
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-7.6 to 8.2
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Time to Recovery to Day 28 (Week 4)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Tocilizumab (TCZ) mITT Arm Placebo Modified Intent-to-Treat (mITT) Arm
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 294 144
Median (95% Confidence Interval)
Unit of Measure: Days
16.0
(12.0 to 21.0)
24.0 [1] 
(18.0 to NA)
[1]
NA = Value not estimable (NE) due to an insufficient number of events.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) mITT Arm, Placebo Modified Intent-to-Treat (mITT) Arm
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0528
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.307
Confidence Interval (2-Sided) 95%
1.00 to 1.72
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Duration of Supplemental Oxygen to Day 28 (Week 4)
Hide Description Participants who died by Day 28 were assigned a duration of 28 days of supplemental oxygen.
Time Frame Up to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Tocilizumab (TCZ) mITT Arm Placebo Modified Intent-to-Treat (mITT) Arm
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 294 144
Median (95% Confidence Interval)
Unit of Measure: Days
26.5
(19.0 to 28.0)
28.0
(26.0 to 28.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) mITT Arm, Placebo Modified Intent-to-Treat (mITT) Arm
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0477
Comments [Not Specified]
Method Van Elteren test
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -1.5
Confidence Interval (2-Sided) 95%
-9.0 to 0.5
Estimation Comments [Not Specified]
Time Frame 60 days
Adverse Event Reporting Description The safety-evaluable population consisted of all participants who received any amount of study medication. Participants are grouped according to the treatment first received rather than the treatment assigned at randomization.
 
Arm/Group Title Placebo Arm (Safety-Evaluable Population) Tocilizumab (TCZ) Arm (Safety-Evaluable Population)
Hide Arm/Group Description The safety-evaluable population consisted of all participants who received any amount of study medication. Participants are grouped according to the treatment first received rather than the treatment assigned at randomization. The safety-evaluable population consisted of all participants who received any amount of study medication. Participants are grouped according to the treatment first received rather than the treatment assigned at randomization.
All-Cause Mortality
Placebo Arm (Safety-Evaluable Population) Tocilizumab (TCZ) Arm (Safety-Evaluable Population)
Affected / at Risk (%) Affected / at Risk (%)
Total   36/143 (25.17%)      72/295 (24.41%)    
Hide Serious Adverse Events
Placebo Arm (Safety-Evaluable Population) Tocilizumab (TCZ) Arm (Safety-Evaluable Population)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   64/143 (44.76%)      116/295 (39.32%)    
Blood and lymphatic system disorders     
Coagulopathy * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Eosinophilia * 1  1/143 (0.70%)  1 0/295 (0.00%)  0
Leukocytosis * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Neutropenia * 1  0/143 (0.00%)  0 4/295 (1.36%)  4
Pancytopenia * 1  1/143 (0.70%)  1 0/295 (0.00%)  0
Thrombocytopenia * 1  1/143 (0.70%)  1 1/295 (0.34%)  1
Cardiac disorders     
Acute myocardial infarction * 1  1/143 (0.70%)  1 1/295 (0.34%)  1
Angina unstable * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Atrial fibrillation * 1  0/143 (0.00%)  0 3/295 (1.02%)  3
Atrioventricular block complete * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Bradycardia * 1  1/143 (0.70%)  1 0/295 (0.00%)  0
Bundle branch block right * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Cardiac arrest * 1  5/143 (3.50%)  6 4/295 (1.36%)  4
Cardiac ventricular thrombosis * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Cardio-respiratory arrest * 1  0/143 (0.00%)  0 2/295 (0.68%)  2
Left ventricular failure * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Pulseless electrical activity * 1  2/143 (1.40%)  2 2/295 (0.68%)  2
Stress cardiomyopathy * 1  1/143 (0.70%)  1 0/295 (0.00%)  0
Ventricular arrhythmia * 1  1/143 (0.70%)  1 0/295 (0.00%)  0
Gastrointestinal disorders     
Abdominal hernia perforation * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Gastrointestinal haemorrhage * 1  1/143 (0.70%)  1 0/295 (0.00%)  0
Lower gastrointestinal haemorrhage * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Melaena * 1  1/143 (0.70%)  1 2/295 (0.68%)  2
Mouth haemorrhage * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Pancreatitis * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Retroperitoneal haemorrhage * 1  0/143 (0.00%)  0 2/295 (0.68%)  2
Small intestinal obstruction * 1  1/143 (0.70%)  1 0/295 (0.00%)  0
General disorders     
Multiple organ dysfunction syndrome * 1  1/143 (0.70%)  1 5/295 (1.69%)  5
Pyrexia * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Systemic inflammatory response syndrome * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Hepatobiliary disorders     
Cholecystitis * 1  1/143 (0.70%)  1 0/295 (0.00%)  0
Hepatic failure * 1  1/143 (0.70%)  1 0/295 (0.00%)  0
Hepatic function abnormal * 1  1/143 (0.70%)  1 0/295 (0.00%)  0
Ischaemic hepatitis * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Infections and infestations     
Bacteraemia * 1  3/143 (2.10%)  3 3/295 (1.02%)  3
Bacterial sepsis * 1  0/143 (0.00%)  0 3/295 (1.02%)  3
Bronchitis * 1  1/143 (0.70%)  1 0/295 (0.00%)  0
COVID-19 * 1  2/143 (1.40%)  2 14/295 (4.75%)  14
COVID-19 pneumonia * 1  20/143 (13.99%)  20 36/295 (12.20%)  36
Candida infection * 1  1/143 (0.70%)  1 0/295 (0.00%)  0
Cytomegalovirus hepatitis * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Device related infection * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Empyema * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Enterobacter pneumonia * 1  1/143 (0.70%)  1 1/295 (0.34%)  1
Escherichia infection * 1  1/143 (0.70%)  1 0/295 (0.00%)  0
Infection * 1  1/143 (0.70%)  1 0/295 (0.00%)  0
Osteomyelitis * 1  1/143 (0.70%)  1 0/295 (0.00%)  0
Pneumocystis jirovecii pneumonia * 1  1/143 (0.70%)  1 0/295 (0.00%)  0
Pneumonia * 1  4/143 (2.80%)  5 7/295 (2.37%)  8
Pneumonia bacterial * 1  2/143 (1.40%)  2 6/295 (2.03%)  6
Pneumonia escherichia * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Pneumonia staphylococcal * 1  1/143 (0.70%)  1 1/295 (0.34%)  1
Pseudomonal sepsis * 1  1/143 (0.70%)  1 0/295 (0.00%)  0
Sepsis * 1  4/143 (2.80%)  4 3/295 (1.02%)  3
Septic shock * 1  7/143 (4.90%)  8 7/295 (2.37%)  7
Staphylococcal infection * 1  1/143 (0.70%)  1 1/295 (0.34%)  1
Stenotrophomonas infection * 1  1/143 (0.70%)  1 0/295 (0.00%)  0
Streptococcal bacteraemia * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Tracheobronchitis bacterial * 1  1/143 (0.70%)  1 0/295 (0.00%)  0
Urinary tract infection * 1  0/143 (0.00%)  0 2/295 (0.68%)  2
Urosepsis * 1  1/143 (0.70%)  1 1/295 (0.34%)  1
Injury, poisoning and procedural complications     
Fall * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Fracture * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Post procedural haemorrhage * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Transfusion-related acute lung injury * 1  1/143 (0.70%)  1 0/295 (0.00%)  0
Investigations     
Aspartate aminotransferase increased * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Citrobacter test positive * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Enterococcus test positive * 1  1/143 (0.70%)  1 0/295 (0.00%)  0
Hepatic enzyme increased * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Metabolism and nutrition disorders     
Acidosis * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Diabetic ketoacidosis * 1  1/143 (0.70%)  1 0/295 (0.00%)  0
Fluid overload * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Hyperglycaemia * 1  1/143 (0.70%)  1 0/295 (0.00%)  0
Hyperkalaemia * 1  1/143 (0.70%)  1 0/295 (0.00%)  0
Hypoglycaemia * 1  1/143 (0.70%)  1 0/295 (0.00%)  0
Metabolic acidosis * 1  1/143 (0.70%)  1 0/295 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Bursitis * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Compartment syndrome * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Nervous system disorders     
Cerebral infarction * 1  1/143 (0.70%)  1 0/295 (0.00%)  0
Depressed level of consciousness * 1  1/143 (0.70%)  1 0/295 (0.00%)  0
Haemorrhagic transformation stroke * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Seizure * 1  1/143 (0.70%)  1 1/295 (0.34%)  1
Subarachnoid haemorrhage * 1  1/143 (0.70%)  1 0/295 (0.00%)  0
Psychiatric disorders     
Delirium * 1  1/143 (0.70%)  1 2/295 (0.68%)  2
Renal and urinary disorders     
Acute kidney injury * 1  4/143 (2.80%)  4 10/295 (3.39%)  10
Renal failure * 1  2/143 (1.40%)  2 2/295 (0.68%)  2
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome * 1  2/143 (1.40%)  2 4/295 (1.36%)  4
Acute respiratory failure * 1  2/143 (1.40%)  2 2/295 (0.68%)  2
Aspiration * 1  1/143 (0.70%)  1 0/295 (0.00%)  0
Haemothorax * 1  0/143 (0.00%)  0 1/295 (0.34%)  2
Hypoxia * 1  3/143 (2.10%)  3 0/295 (0.00%)  0
Lung consolidation * 1  1/143 (0.70%)  1 0/295 (0.00%)  0
Obstructive airways disorder * 1  1/143 (0.70%)  1 0/295 (0.00%)  0
Pharyngeal haemorrhage * 1  2/143 (1.40%)  2 0/295 (0.00%)  0
Pneumonia aspiration * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Pneumothorax * 1  3/143 (2.10%)  3 4/295 (1.36%)  5
Pneumothorax spontaneous * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Pulmonary embolism * 1  2/143 (1.40%)  2 5/295 (1.69%)  5
Respiratory disorder * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Respiratory failure * 1  6/143 (4.20%)  6 5/295 (1.69%)  5
Vascular disorders     
Arterial haemorrhage * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Deep vein thrombosis * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Haematoma * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Haemorrhage * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Hypertension * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Hypotension * 1  1/143 (0.70%)  1 1/295 (0.34%)  1
Peripheral embolism * 1  0/143 (0.00%)  0 1/295 (0.34%)  1
Shock haemorrhagic * 1  1/143 (0.70%)  1 2/295 (0.68%)  2
1
Term from vocabulary, MedDRA v23.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Arm (Safety-Evaluable Population) Tocilizumab (TCZ) Arm (Safety-Evaluable Population)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   29/143 (20.28%)      83/295 (28.14%)    
Blood and lymphatic system disorders     
Anaemia * 1  10/143 (6.99%)  10 17/295 (5.76%)  17
Gastrointestinal disorders     
Constipation * 1  8/143 (5.59%)  8 18/295 (6.10%)  18
Diarrhoea * 1  3/143 (2.10%)  3 18/295 (6.10%)  18
Infections and infestations     
Pneumonia * 1  8/143 (5.59%)  12 10/295 (3.39%)  10
Urinary tract infection * 1  5/143 (3.50%)  6 22/295 (7.46%)  22
Vascular disorders     
Hypertension * 1  3/143 (2.10%)  4 20/295 (6.78%)  24
1
Term from vocabulary, MedDRA v23.0
*
Indicates events were collected by non-systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 1-800-821-8590
EMail: genentech@druginfo.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT04320615    
Other Study ID Numbers: WA42380
2020-001154-22 ( EudraCT Number )
First Submitted: March 23, 2020
First Posted: March 25, 2020
Results First Submitted: June 23, 2021
Results First Posted: June 30, 2021
Last Update Posted: June 30, 2021