Trial Outcomes & Findings for A Study to Investigate Intravenous Tocilizumab in Participants With Moderate to Severe COVID-19 Pneumonia (NCT NCT04363736)
NCT ID: NCT04363736
Last Updated: 2022-08-31
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
97 participants
Primary outcome timeframe
Days 0-28. Participants received a second dose within 8-24 hours after the initial infusion of TCZ at the discretion of the investigator upon clinically significant demonstration of worsening signs or symptoms.
Results posted on
2022-08-31
Participant Flow
Participant milestones
| Measure |
TCZ 4 mg/kg
Participants received intravenous (IV) tocilizumab (TCZ) at a dose of 4 mg/kg in addition to standard-of-care treatment.
|
TCZ 8 mg/kg
Participants received IV tocilizumab (TCZ) at a dose of 8 mg/kg in addition to standard-of-care treatment.
|
|---|---|---|
|
Overall Study
STARTED
|
49
|
48
|
|
Overall Study
COMPLETED
|
30
|
35
|
|
Overall Study
NOT COMPLETED
|
19
|
13
|
Reasons for withdrawal
| Measure |
TCZ 4 mg/kg
Participants received intravenous (IV) tocilizumab (TCZ) at a dose of 4 mg/kg in addition to standard-of-care treatment.
|
TCZ 8 mg/kg
Participants received IV tocilizumab (TCZ) at a dose of 8 mg/kg in addition to standard-of-care treatment.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
10
|
7
|
|
Overall Study
Death
|
8
|
6
|
Baseline Characteristics
A Study to Investigate Intravenous Tocilizumab in Participants With Moderate to Severe COVID-19 Pneumonia
Baseline characteristics by cohort
| Measure |
TCZ 4 mg/kg
n=49 Participants
Participants received intravenous (IV) tocilizumab (TCZ) at a dose of 4 mg/kg in addition to standard-of-care treatment.
|
TCZ 8 mg/kg
n=48 Participants
Participants received IV tocilizumab (TCZ) at a dose of 8 mg/kg in addition to standard-of-care treatment.
|
Total
n=97 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
56.8 Years
STANDARD_DEVIATION 14.3 • n=5 Participants
|
59.8 Years
STANDARD_DEVIATION 14.6 • n=7 Participants
|
58.3 Years
STANDARD_DEVIATION 14.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
22 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
40 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
27 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
57 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
11 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
35 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
67 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
20 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
15 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
8 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Days 0-28. Participants received a second dose within 8-24 hours after the initial infusion of TCZ at the discretion of the investigator upon clinically significant demonstration of worsening signs or symptoms.Population: The PK population consisted of all randomized participants who received any amount of study drug with at least one valid pharmacokinetic (PK) result. Participants were analyzed according to treatment received.
Outcome measures
| Measure |
TCZ 4 mg/kg
n=35 Participants
Participants received intravenous (IV) tocilizumab (TCZ) at a dose of 4 mg/kg in addition to standard-of-care treatment.
|
TCZ 8 mg/kg
n=38 Participants
Participants received IV tocilizumab (TCZ) at a dose of 8 mg/kg in addition to standard-of-care treatment.
|
|---|---|---|
|
Area Under the Curve From Day 0-28 (AUC0-d28) of Tocilizumab)
One dose
|
371 µg/mL*day
Interval 196.0 to 1040.0
|
849 µg/mL*day
Interval 471.0 to 1500.0
|
|
Area Under the Curve From Day 0-28 (AUC0-d28) of Tocilizumab)
Two doses
|
837 µg/mL*day
Interval 592.0 to 1480.0
|
1330 µg/mL*day
Interval 1130.0 to 1810.0
|
PRIMARY outcome
Timeframe: Baseline - Day 60. Participants received a second dose within 8-24 hours after the initial infusion of TCZ at the discretion of the investigator upon clinically significant demonstration of worsening signs or symptoms.Population: The PK population consisted of all randomized participants who received any amount of study drug with at least one valid pharmacokinetic (PK) result. Participants were analyzed according to treatment received.
Outcome measures
| Measure |
TCZ 4 mg/kg
n=35 Participants
Participants received intravenous (IV) tocilizumab (TCZ) at a dose of 4 mg/kg in addition to standard-of-care treatment.
|
TCZ 8 mg/kg
n=38 Participants
Participants received IV tocilizumab (TCZ) at a dose of 8 mg/kg in addition to standard-of-care treatment.
|
|---|---|---|
|
Maximum Serum Concentration (Cmax) of Tocilizumab
One dose
|
82.2 µg/mL
Interval 48.8 to 134.0
|
159 µg/mL
Interval 101.0 to 234.0
|
|
Maximum Serum Concentration (Cmax) of Tocilizumab
Two doses
|
150 µg/mL
Interval 110.0 to 203.0
|
228 µg/mL
Interval 198.0 to 363.0
|
PRIMARY outcome
Timeframe: Baseline - Day 60. Participants received a second dose within 8-24 hours after the initial infusion of TCZ at the discretion of the investigator upon clinically significant demonstration of worsening signs or symptoms.Population: The PK population consisted of all randomized participants who received any amount of study drug with at least one valid pharmacokinetic (PK) result. Participants were analyzed according to treatment received.
Outcome measures
| Measure |
TCZ 4 mg/kg
n=35 Participants
Participants received intravenous (IV) tocilizumab (TCZ) at a dose of 4 mg/kg in addition to standard-of-care treatment.
|
TCZ 8 mg/kg
n=38 Participants
Participants received IV tocilizumab (TCZ) at a dose of 8 mg/kg in addition to standard-of-care treatment.
|
|---|---|---|
|
Clearance (CL) of Tocilizumab
One dose
|
0.451 L/day
Interval 0.261 to 0.697
|
0.487 L/day
Interval 0.179 to 1.16
|
|
Clearance (CL) of Tocilizumab
Two doses
|
0.468 L/day
Interval 0.327 to 0.701
|
0.629 L/day
Interval 0.376 to 1.02
|
PRIMARY outcome
Timeframe: Baseline - Day 60. Participants received a second dose within 8-24 hours after the initial infusion of TCZ at the discretion of the investigator upon clinically significant demonstration of worsening signs or symptoms.Population: The PK population consisted of all randomized participants who received any amount of study drug with at least one valid pharmacokinetic (PK) result. Participants were analyzed according to treatment received.
Outcome measures
| Measure |
TCZ 4 mg/kg
n=35 Participants
Participants received intravenous (IV) tocilizumab (TCZ) at a dose of 4 mg/kg in addition to standard-of-care treatment.
|
TCZ 8 mg/kg
n=38 Participants
Participants received IV tocilizumab (TCZ) at a dose of 8 mg/kg in addition to standard-of-care treatment.
|
|---|---|---|
|
Volume of the Central Compartment (Vc) of Tocilizumab
One dose
|
4.14 L
Interval 2.47 to 7.11
|
4.34 L
Interval 3.08 to 7.88
|
|
Volume of the Central Compartment (Vc) of Tocilizumab
Two doses
|
4.2 L
Interval 2.54 to 5.17
|
4.57 L
Interval 3.59 to 7.27
|
PRIMARY outcome
Timeframe: Baseline - Day 60Population: Modified intent-to-treat population (mITT): All randomized participants who received any amount of study drug. Participants are analyzed according to the treatment assigned at randomization.
Outcome measures
| Measure |
TCZ 4 mg/kg
n=49 Participants
Participants received intravenous (IV) tocilizumab (TCZ) at a dose of 4 mg/kg in addition to standard-of-care treatment.
|
TCZ 8 mg/kg
n=48 Participants
Participants received IV tocilizumab (TCZ) at a dose of 8 mg/kg in addition to standard-of-care treatment.
|
|---|---|---|
|
Serum Concentration of C-reactive Protein (CRP) Following Administration of IV TCZ
Baseline
|
125.04 mg/L
Geometric Coefficient of Variation 121.5
|
115.77 mg/L
Geometric Coefficient of Variation 128.7
|
|
Serum Concentration of C-reactive Protein (CRP) Following Administration of IV TCZ
Day 1 - 15 min post-dose
|
124.67 mg/L
Geometric Coefficient of Variation 118.8
|
109.19 mg/L
Geometric Coefficient of Variation 134.4
|
|
Serum Concentration of C-reactive Protein (CRP) Following Administration of IV TCZ
Day 1 - pre-dose 2nd infusion
|
123.49 mg/L
Geometric Coefficient of Variation 68.0
|
118.83 mg/L
Geometric Coefficient of Variation 45.1
|
|
Serum Concentration of C-reactive Protein (CRP) Following Administration of IV TCZ
Day 1 - 15 min post-dose 2nd infusion
|
116.89 mg/L
Geometric Coefficient of Variation 62.4
|
112.97 mg/L
Geometric Coefficient of Variation 53.4
|
|
Serum Concentration of C-reactive Protein (CRP) Following Administration of IV TCZ
Day 2 - 24 hours post-dose
|
85.75 mg/L
Geometric Coefficient of Variation 133.1
|
86.01 mg/L
Geometric Coefficient of Variation 124.2
|
|
Serum Concentration of C-reactive Protein (CRP) Following Administration of IV TCZ
Day 3
|
41.56 mg/L
Geometric Coefficient of Variation 129.6
|
39.17 mg/L
Geometric Coefficient of Variation 134.8
|
|
Serum Concentration of C-reactive Protein (CRP) Following Administration of IV TCZ
Day 7
|
7.27 mg/L
Geometric Coefficient of Variation 145.1
|
5.62 mg/L
Geometric Coefficient of Variation 188.3
|
|
Serum Concentration of C-reactive Protein (CRP) Following Administration of IV TCZ
Day 14
|
4.42 mg/L
Geometric Coefficient of Variation 554.8
|
0.87 mg/L
Geometric Coefficient of Variation 95.0
|
|
Serum Concentration of C-reactive Protein (CRP) Following Administration of IV TCZ
Day 21
|
3.73 mg/L
Geometric Coefficient of Variation 552.5
|
1.75 mg/L
Geometric Coefficient of Variation 1681.6
|
|
Serum Concentration of C-reactive Protein (CRP) Following Administration of IV TCZ
Day 28
|
3.01 mg/L
Geometric Coefficient of Variation 483.0
|
2.57 mg/L
Geometric Coefficient of Variation 2251.1
|
|
Serum Concentration of C-reactive Protein (CRP) Following Administration of IV TCZ
Day 35
|
2.12 mg/L
Geometric Coefficient of Variation 234.5
|
11.25 mg/L
Geometric Coefficient of Variation 1543.9
|
|
Serum Concentration of C-reactive Protein (CRP) Following Administration of IV TCZ
Day 60
|
2.41 mg/L
Geometric Coefficient of Variation 256.0
|
1.61 mg/L
Geometric Coefficient of Variation 154.1
|
PRIMARY outcome
Timeframe: Baseline - Day 60Population: Modified intent-to-treat population (mITT): All randomized participants who received any amount of study drug. Participants are analyzed according to the treatment assigned at randomization.
Outcome measures
| Measure |
TCZ 4 mg/kg
n=49 Participants
Participants received intravenous (IV) tocilizumab (TCZ) at a dose of 4 mg/kg in addition to standard-of-care treatment.
|
TCZ 8 mg/kg
n=48 Participants
Participants received IV tocilizumab (TCZ) at a dose of 8 mg/kg in addition to standard-of-care treatment.
|
|---|---|---|
|
Serum Concentration of Ferritin Following Administration of IV TCZ
Baseline
|
2081.46 pmol/L
Geometric Coefficient of Variation 162.4
|
1821.19 pmol/L
Geometric Coefficient of Variation 174.0
|
|
Serum Concentration of Ferritin Following Administration of IV TCZ
Day 2 - 24 hours post-dose
|
2282.62 pmol/L
Geometric Coefficient of Variation 191.3
|
1938.19 pmol/L
Geometric Coefficient of Variation 154.6
|
|
Serum Concentration of Ferritin Following Administration of IV TCZ
Day 3
|
2016.10 pmol/L
Geometric Coefficient of Variation 128.0
|
2060.41 pmol/L
Geometric Coefficient of Variation 131.2
|
|
Serum Concentration of Ferritin Following Administration of IV TCZ
Day 7
|
1760.82 pmol/L
Geometric Coefficient of Variation 170.3
|
1494.76 pmol/L
Geometric Coefficient of Variation 86.7
|
|
Serum Concentration of Ferritin Following Administration of IV TCZ
Day 14
|
1108.34 pmol/L
Geometric Coefficient of Variation 127.2
|
720.66 pmol/L
Geometric Coefficient of Variation 102.3
|
|
Serum Concentration of Ferritin Following Administration of IV TCZ
Day 21
|
754.24 pmol/L
Geometric Coefficient of Variation 138.4
|
558.57 pmol/L
Geometric Coefficient of Variation 119.0
|
|
Serum Concentration of Ferritin Following Administration of IV TCZ
Day 28
|
393.46 pmol/L
Geometric Coefficient of Variation 139.3
|
519.51 pmol/L
Geometric Coefficient of Variation 139.0
|
|
Serum Concentration of Ferritin Following Administration of IV TCZ
Day 35
|
309.23 pmol/L
Geometric Coefficient of Variation 105.5
|
291.24 pmol/L
Geometric Coefficient of Variation 66.5
|
|
Serum Concentration of Ferritin Following Administration of IV TCZ
Day 60
|
282.85 pmol/L
Geometric Coefficient of Variation 148.7
|
246.17 pmol/L
Geometric Coefficient of Variation 171.4
|
PRIMARY outcome
Timeframe: Baseline - Day 60Population: Modified intent-to-treat population (mITT): All randomized participants who received any amount of study drug. Participants are analyzed according to the treatment assigned at randomization. Participants at Day 2 15-min post-dose were those that received a second dose of TCZ and had PK taken after that second dose.
Outcome measures
| Measure |
TCZ 4 mg/kg
n=49 Participants
Participants received intravenous (IV) tocilizumab (TCZ) at a dose of 4 mg/kg in addition to standard-of-care treatment.
|
TCZ 8 mg/kg
n=48 Participants
Participants received IV tocilizumab (TCZ) at a dose of 8 mg/kg in addition to standard-of-care treatment.
|
|---|---|---|
|
Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R) Following Administration of IV TCZ
Baseline
|
35869.87 ng/L
Geometric Coefficient of Variation 29.1
|
35331.04 ng/L
Geometric Coefficient of Variation 31.3
|
|
Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R) Following Administration of IV TCZ
Day 1 - 15 min post-dose
|
47037.59 ng/L
Geometric Coefficient of Variation 56.1
|
40928.43 ng/L
Geometric Coefficient of Variation 46.4
|
|
Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R) Following Administration of IV TCZ
Day 2 - 15 min post-dose
|
80880.16 ng/L
Geometric Coefficient of Variation 24.9
|
44300.00 ng/L
Geometric Coefficient of Variation NA
CV not available for a single value.
|
|
Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R) Following Administration of IV TCZ
Day 2 - 24 hours post-dose
|
97280.14 ng/L
Geometric Coefficient of Variation 31.3
|
90057.53 ng/L
Geometric Coefficient of Variation 28.8
|
|
Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R) Following Administration of IV TCZ
Day 3
|
139128.70 ng/L
Geometric Coefficient of Variation 26.5
|
139528.82 ng/L
Geometric Coefficient of Variation 30.3
|
|
Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R) Following Administration of IV TCZ
Day 7
|
261637.28 ng/L
Geometric Coefficient of Variation 30.2
|
263899.86 ng/L
Geometric Coefficient of Variation 26.7
|
|
Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R) Following Administration of IV TCZ
Day 14
|
258484.08 ng/L
Geometric Coefficient of Variation 52.3
|
339661.18 ng/L
Geometric Coefficient of Variation 19.6
|
|
Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R) Following Administration of IV TCZ
Day 21
|
162025.68 ng/L
Geometric Coefficient of Variation 73.1
|
265981.84 ng/L
Geometric Coefficient of Variation 49.1
|
|
Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R) Following Administration of IV TCZ
Day 28
|
82508.76 ng/L
Geometric Coefficient of Variation 102.6
|
162795.31 ng/L
Geometric Coefficient of Variation 106.0
|
|
Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R) Following Administration of IV TCZ
Day 35
|
80425.91 ng/L
Geometric Coefficient of Variation 138.7
|
144868.00 ng/L
Geometric Coefficient of Variation 105.4
|
|
Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R) Following Administration of IV TCZ
Day 60
|
36049.91 ng/L
Geometric Coefficient of Variation 21.7
|
34258.34 ng/L
Geometric Coefficient of Variation 22.2
|
PRIMARY outcome
Timeframe: Baseline - Day 60Population: Modified intent-to-treat population (mITT): All randomized participants who received any amount of study drug. Participants are analyzed according to the treatment assigned at randomization.
Outcome measures
| Measure |
TCZ 4 mg/kg
n=49 Participants
Participants received intravenous (IV) tocilizumab (TCZ) at a dose of 4 mg/kg in addition to standard-of-care treatment.
|
TCZ 8 mg/kg
n=48 Participants
Participants received IV tocilizumab (TCZ) at a dose of 8 mg/kg in addition to standard-of-care treatment.
|
|---|---|---|
|
Serum Concentration of Interleukin-6 (IL-6) Following Administration of IV TCZ
Day 1 - 15 min post-dose
|
336.99 ng/L
Geometric Coefficient of Variation 248.8
|
325.96 ng/L
Geometric Coefficient of Variation 236.4
|
|
Serum Concentration of Interleukin-6 (IL-6) Following Administration of IV TCZ
Day 2 - 15 min post-dose
|
292.69 ng/L
Geometric Coefficient of Variation 159.8
|
638.00 ng/L
Geometric Coefficient of Variation NA
CV not available for a single value.
|
|
Serum Concentration of Interleukin-6 (IL-6) Following Administration of IV TCZ
Day 2 - 24 hours post-dose
|
733.99 ng/L
Geometric Coefficient of Variation 226.5
|
757.17 ng/L
Geometric Coefficient of Variation 172.4
|
|
Serum Concentration of Interleukin-6 (IL-6) Following Administration of IV TCZ
Day 3
|
748.82 ng/L
Geometric Coefficient of Variation 394.2
|
743.84 ng/L
Geometric Coefficient of Variation 263.0
|
|
Serum Concentration of Interleukin-6 (IL-6) Following Administration of IV TCZ
Day 7
|
545.44 ng/L
Geometric Coefficient of Variation 315.9
|
589.21 ng/L
Geometric Coefficient of Variation 429.0
|
|
Serum Concentration of Interleukin-6 (IL-6) Following Administration of IV TCZ
Day 14
|
234.88 ng/L
Geometric Coefficient of Variation 332.2
|
125.64 ng/L
Geometric Coefficient of Variation 345.9
|
|
Serum Concentration of Interleukin-6 (IL-6) Following Administration of IV TCZ
Day 21
|
49.16 ng/L
Geometric Coefficient of Variation 482.7
|
91.86 ng/L
Geometric Coefficient of Variation 465.9
|
|
Serum Concentration of Interleukin-6 (IL-6) Following Administration of IV TCZ
Day 28
|
5.73 ng/L
Geometric Coefficient of Variation NA
Geometric CV not reported when more than 1/3 of post-dose PK samples are below the limit of quantitation.
|
28.66 ng/L
Geometric Coefficient of Variation 371.7
|
|
Serum Concentration of Interleukin-6 (IL-6) Following Administration of IV TCZ
Day 35
|
7.68 ng/L
Geometric Coefficient of Variation 361.9
|
39.79 ng/L
Geometric Coefficient of Variation 503.0
|
|
Serum Concentration of Interleukin-6 (IL-6) Following Administration of IV TCZ
Day 60
|
2.52 ng/L
Geometric Coefficient of Variation NA
Geometric CV not reported when more than 1/3 of post-dose PK samples are below the limit of quantitation.
|
2.28 ng/L
Geometric Coefficient of Variation NA
Geometric CV not reported when more than 1/3 of post-dose PK samples are below the limit of quantitation.
|
SECONDARY outcome
Timeframe: Up to Day 60Population: The safety population included all randomized participants who received any amount of study drug, with participants analyzed according to the treatment received.
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Outcome measures
| Measure |
TCZ 4 mg/kg
n=49 Participants
Participants received intravenous (IV) tocilizumab (TCZ) at a dose of 4 mg/kg in addition to standard-of-care treatment.
|
TCZ 8 mg/kg
n=48 Participants
Participants received IV tocilizumab (TCZ) at a dose of 8 mg/kg in addition to standard-of-care treatment.
|
|---|---|---|
|
Pecentage of Participants With Adverse Events
|
57.1 Percentage of Participants
|
45.8 Percentage of Participants
|
SECONDARY outcome
Timeframe: Baseline - Day 60Population: The safety population included all randomized participants who received any amount of study drug, with participants analyzed according to the treatment received.
Outcome measures
| Measure |
TCZ 4 mg/kg
n=49 Participants
Participants received intravenous (IV) tocilizumab (TCZ) at a dose of 4 mg/kg in addition to standard-of-care treatment.
|
TCZ 8 mg/kg
n=48 Participants
Participants received IV tocilizumab (TCZ) at a dose of 8 mg/kg in addition to standard-of-care treatment.
|
|---|---|---|
|
Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) (COVID-19) Viral Load Over Time
Day 6
|
0.91 copies/µL
Interval 0.1 to 41683.2
|
2.56 copies/µL
Interval 0.1 to 13318.7
|
|
Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) (COVID-19) Viral Load Over Time
Baseline
|
30.56 copies/µL
Interval 0.1 to 14458.9
|
8.51 copies/µL
Interval 0.1 to 132429.0
|
|
Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) (COVID-19) Viral Load Over Time
Day 2
|
8.38 copies/µL
Interval 0.1 to 6328.1
|
7.90 copies/µL
Interval 0.1 to 264252.7
|
|
Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) (COVID-19) Viral Load Over Time
Day 3
|
3.82 copies/µL
Interval 0.1 to 338006.1
|
4.46 copies/µL
Interval 0.1 to 135875.7
|
|
Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) (COVID-19) Viral Load Over Time
Day 4
|
2.44 copies/µL
Interval 0.1 to 17142.1
|
2.73 copies/µL
Interval 0.1 to 159013.2
|
|
Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) (COVID-19) Viral Load Over Time
Day 5
|
8.74 copies/µL
Interval 0.1 to 2930.4
|
5.39 copies/µL
Interval 0.1 to 59216.3
|
|
Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) (COVID-19) Viral Load Over Time
Day 7
|
0.49 copies/µL
Interval 0.1 to 11609.3
|
1.47 copies/µL
Interval 0.1 to 14185.5
|
|
Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) (COVID-19) Viral Load Over Time
Day 10
|
2.56 copies/µL
Interval 0.1 to 149.3
|
0.59 copies/µL
Interval 0.1 to 556.2
|
|
Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) (COVID-19) Viral Load Over Time
Day 14
|
0.14 copies/µL
Interval 0.1 to 26.5
|
0.18 copies/µL
Interval 0.1 to 436.5
|
|
Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) (COVID-19) Viral Load Over Time
Day 21
|
0.1 copies/µL
Interval 0.1 to 39.6
|
0.12 copies/µL
Interval 0.1 to 56.4
|
|
Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) (COVID-19) Viral Load Over Time
Day 28
|
0.16 copies/µL
Interval 0.1 to 3.6
|
0.12 copies/µL
Interval 0.1 to 3.4
|
|
Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) (COVID-19) Viral Load Over Time
Day 35
|
0.1 copies/µL
Interval 0.1 to 0.2
|
0.12 copies/µL
Interval 0.1 to 5.6
|
|
Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) (COVID-19) Viral Load Over Time
Day 45
|
0.1 copies/µL
Interval 0.1 to 0.1
|
0.1 copies/µL
Interval 0.1 to 0.1
|
|
Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) (COVID-19) Viral Load Over Time
Early withdrawal
|
—
|
0.1 copies/µL
Interval 0.1 to 0.1
|
|
Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) (COVID-19) Viral Load Over Time
Day 60
|
0.1 copies/µL
Interval 0.1 to 0.1
|
0.1 copies/µL
Interval 0.1 to 0.3
|
SECONDARY outcome
Timeframe: Up to Day 28Population: Only participants with at least one virology assessment were included in the analysis.
Time to Real-Time Polymerase Chain Reaction (RT-PCR) virus negativity was defined as the number of days from the first dose of study drug to when a negative RT-PCR SARS-CoV-2 assessment result was observed. Results are presented as a cumulative incidence function (CIF) with death as a competing risk.
Outcome measures
| Measure |
TCZ 4 mg/kg
n=49 Participants
Participants received intravenous (IV) tocilizumab (TCZ) at a dose of 4 mg/kg in addition to standard-of-care treatment.
|
TCZ 8 mg/kg
n=48 Participants
Participants received IV tocilizumab (TCZ) at a dose of 8 mg/kg in addition to standard-of-care treatment.
|
|---|---|---|
|
Time to Real-Time Polymerase Chain Reaction (RT-PCR) Virus Negativity
CIF for event on Day 7
|
0.3389 Probability
|
0.2874 Probability
|
|
Time to Real-Time Polymerase Chain Reaction (RT-PCR) Virus Negativity
CIF for death on Day 7
|
0.0665 Probability
|
0.0000 Probability
|
|
Time to Real-Time Polymerase Chain Reaction (RT-PCR) Virus Negativity
CIF for event on Day 14
|
0.5068 Probability
|
0.5727 Probability
|
|
Time to Real-Time Polymerase Chain Reaction (RT-PCR) Virus Negativity
CIF for death on Day 14
|
0.1024 Probability
|
0.0884 Probability
|
|
Time to Real-Time Polymerase Chain Reaction (RT-PCR) Virus Negativity
CIF for event on Day 21
|
0.5068 Probability
|
0.5727 Probability
|
|
Time to Real-Time Polymerase Chain Reaction (RT-PCR) Virus Negativity
CIF for death on Day 21
|
0.1497 Probability
|
0.1280 Probability
|
|
Time to Real-Time Polymerase Chain Reaction (RT-PCR) Virus Negativity
CIF for event on Day 28
|
0.5730 Probability
|
0.6327 Probability
|
|
Time to Real-Time Polymerase Chain Reaction (RT-PCR) Virus Negativity
CIF for death on Day 28
|
0.3420 Probability
|
0.1793 Probability
|
SECONDARY outcome
Timeframe: Up to Day 60Outcome measures
| Measure |
TCZ 4 mg/kg
n=49 Participants
Participants received intravenous (IV) tocilizumab (TCZ) at a dose of 4 mg/kg in addition to standard-of-care treatment.
|
TCZ 8 mg/kg
n=48 Participants
Participants received IV tocilizumab (TCZ) at a dose of 8 mg/kg in addition to standard-of-care treatment.
|
|---|---|---|
|
Proportion of Participants With Any Post-Treatment Infection
COVID-19 pneumonia
|
6.1 Percentage of Participants
|
2.1 Percentage of Participants
|
|
Proportion of Participants With Any Post-Treatment Infection
Sepsis
|
2.0 Percentage of Participants
|
4.2 Percentage of Participants
|
|
Proportion of Participants With Any Post-Treatment Infection
Septic shock
|
2.0 Percentage of Participants
|
4.2 Percentage of Participants
|
|
Proportion of Participants With Any Post-Treatment Infection
Pneumonia
|
2.0 Percentage of Participants
|
2.1 Percentage of Participants
|
|
Proportion of Participants With Any Post-Treatment Infection
Urinary tract infection
|
2.0 Percentage of Participants
|
2.1 Percentage of Participants
|
|
Proportion of Participants With Any Post-Treatment Infection
Abscess limb
|
2.0 Percentage of Participants
|
0 Percentage of Participants
|
|
Proportion of Participants With Any Post-Treatment Infection
Atypical pneumonia
|
2.0 Percentage of Participants
|
0 Percentage of Participants
|
|
Proportion of Participants With Any Post-Treatment Infection
Pneumonia bacterial
|
2.0 Percentage of Participants
|
0 Percentage of Participants
|
|
Proportion of Participants With Any Post-Treatment Infection
Pneumonia klebsiella
|
2.0 Percentage of Participants
|
0 Percentage of Participants
|
|
Proportion of Participants With Any Post-Treatment Infection
Pneumonia streptococcal
|
2.0 Percentage of Participants
|
0 Percentage of Participants
|
|
Proportion of Participants With Any Post-Treatment Infection
Staphylococcal infection
|
2.0 Percentage of Participants
|
0 Percentage of Participants
|
Adverse Events
TCZ 4 mg/kg
Serious events: 15 serious events
Other events: 4 other events
Deaths: 8 deaths
TCZ 8 mg/kg
Serious events: 12 serious events
Other events: 3 other events
Deaths: 6 deaths
Serious adverse events
| Measure |
TCZ 4 mg/kg
n=49 participants at risk
Participants received intravenous (IV) tocilizumab (TCZ) at a dose of 4 mg/kg in addition to standard-of-care treatment.
|
TCZ 8 mg/kg
n=48 participants at risk
Participants received IV tocilizumab (TCZ) at a dose of 8 mg/kg in addition to standard-of-care treatment.
|
|---|---|---|
|
Blood and lymphatic system disorders
Disseminated intravascular coagulation
|
0.00%
0/49 • Up to Day 60
|
2.1%
1/48 • Number of events 1 • Up to Day 60
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/49 • Up to Day 60
|
2.1%
1/48 • Number of events 1 • Up to Day 60
|
|
Cardiac disorders
Cardiogenic shock
|
0.00%
0/49 • Up to Day 60
|
2.1%
1/48 • Number of events 1 • Up to Day 60
|
|
Gastrointestinal disorders
Diarrhoea
|
4.1%
2/49 • Number of events 2 • Up to Day 60
|
0.00%
0/48 • Up to Day 60
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
2.0%
1/49 • Number of events 1 • Up to Day 60
|
0.00%
0/48 • Up to Day 60
|
|
General disorders
Multiple organ dysfunction syndrome
|
0.00%
0/49 • Up to Day 60
|
2.1%
1/48 • Number of events 1 • Up to Day 60
|
|
Hepatobiliary disorders
Cholecystitis acute
|
2.0%
1/49 • Number of events 1 • Up to Day 60
|
2.1%
1/48 • Number of events 1 • Up to Day 60
|
|
Hepatobiliary disorders
Drug-induced liver injury
|
0.00%
0/49 • Up to Day 60
|
2.1%
1/48 • Number of events 1 • Up to Day 60
|
|
Infections and infestations
Atypical pneumonia
|
2.0%
1/49 • Number of events 1 • Up to Day 60
|
0.00%
0/48 • Up to Day 60
|
|
Infections and infestations
COVID-19 pneumonia
|
6.1%
3/49 • Number of events 3 • Up to Day 60
|
2.1%
1/48 • Number of events 1 • Up to Day 60
|
|
Infections and infestations
Pneumonia
|
2.0%
1/49 • Number of events 1 • Up to Day 60
|
2.1%
1/48 • Number of events 1 • Up to Day 60
|
|
Infections and infestations
Sepsis
|
2.0%
1/49 • Number of events 1 • Up to Day 60
|
2.1%
1/48 • Number of events 1 • Up to Day 60
|
|
Infections and infestations
Septic shock
|
2.0%
1/49 • Number of events 1 • Up to Day 60
|
4.2%
2/48 • Number of events 2 • Up to Day 60
|
|
Infections and infestations
Staphylococcal infection
|
2.0%
1/49 • Number of events 1 • Up to Day 60
|
0.00%
0/48 • Up to Day 60
|
|
Investigations
Sputum culture positive
|
0.00%
0/49 • Up to Day 60
|
2.1%
1/48 • Number of events 1 • Up to Day 60
|
|
Metabolism and nutrition disorders
Failure to thrive
|
4.1%
2/49 • Number of events 2 • Up to Day 60
|
0.00%
0/48 • Up to Day 60
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
2.0%
1/49 • Number of events 1 • Up to Day 60
|
0.00%
0/48 • Up to Day 60
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
2.0%
1/49 • Number of events 1 • Up to Day 60
|
0.00%
0/48 • Up to Day 60
|
|
Nervous system disorders
Cerebral infarction
|
0.00%
0/49 • Up to Day 60
|
2.1%
1/48 • Number of events 1 • Up to Day 60
|
|
Nervous system disorders
Intensive care unit acquired weakness
|
2.0%
1/49 • Number of events 1 • Up to Day 60
|
2.1%
1/48 • Number of events 1 • Up to Day 60
|
|
Psychiatric disorders
Mental status changes
|
2.0%
1/49 • Number of events 1 • Up to Day 60
|
0.00%
0/48 • Up to Day 60
|
|
Renal and urinary disorders
Acute kidney injury
|
2.0%
1/49 • Number of events 1 • Up to Day 60
|
8.3%
4/48 • Number of events 4 • Up to Day 60
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
0.00%
0/49 • Up to Day 60
|
2.1%
1/48 • Number of events 1 • Up to Day 60
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.00%
0/49 • Up to Day 60
|
2.1%
1/48 • Number of events 1 • Up to Day 60
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
2.0%
1/49 • Number of events 1 • Up to Day 60
|
0.00%
0/48 • Up to Day 60
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.0%
1/49 • Number of events 1 • Up to Day 60
|
0.00%
0/48 • Up to Day 60
|
|
Respiratory, thoracic and mediastinal disorders
Hydrothorax
|
0.00%
0/49 • Up to Day 60
|
2.1%
1/48 • Number of events 1 • Up to Day 60
|
|
Respiratory, thoracic and mediastinal disorders
Mediastinal haematoma
|
0.00%
0/49 • Up to Day 60
|
2.1%
1/48 • Number of events 1 • Up to Day 60
|
|
Respiratory, thoracic and mediastinal disorders
Pneumomediastinum
|
0.00%
0/49 • Up to Day 60
|
2.1%
1/48 • Number of events 1 • Up to Day 60
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
2.0%
1/49 • Number of events 1 • Up to Day 60
|
0.00%
0/48 • Up to Day 60
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory acidosis
|
0.00%
0/49 • Up to Day 60
|
2.1%
1/48 • Number of events 1 • Up to Day 60
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/49 • Up to Day 60
|
4.2%
2/48 • Number of events 2 • Up to Day 60
|
|
Skin and subcutaneous tissue disorders
Subcutaneous emphysema
|
0.00%
0/49 • Up to Day 60
|
2.1%
1/48 • Number of events 1 • Up to Day 60
|
|
Vascular disorders
Hypotension
|
2.0%
1/49 • Number of events 1 • Up to Day 60
|
2.1%
1/48 • Number of events 1 • Up to Day 60
|
|
Vascular disorders
Shock
|
0.00%
0/49 • Up to Day 60
|
2.1%
1/48 • Number of events 1 • Up to Day 60
|
|
Vascular disorders
Shock haemorrhagic
|
0.00%
0/49 • Up to Day 60
|
2.1%
1/48 • Number of events 1 • Up to Day 60
|
Other adverse events
| Measure |
TCZ 4 mg/kg
n=49 participants at risk
Participants received intravenous (IV) tocilizumab (TCZ) at a dose of 4 mg/kg in addition to standard-of-care treatment.
|
TCZ 8 mg/kg
n=48 participants at risk
Participants received IV tocilizumab (TCZ) at a dose of 8 mg/kg in addition to standard-of-care treatment.
|
|---|---|---|
|
Investigations
Alanine aminotransferase increased
|
6.1%
3/49 • Number of events 3 • Up to Day 60
|
0.00%
0/48 • Up to Day 60
|
|
Investigations
Aspartate aminotransferase increased
|
6.1%
3/49 • Number of events 3 • Up to Day 60
|
0.00%
0/48 • Up to Day 60
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
2.0%
1/49 • Number of events 1 • Up to Day 60
|
6.2%
3/48 • Number of events 3 • Up to Day 60
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER