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This study will assess the pharmacodynamics, pharmacokinetics, safety and efficacy of two different doses of tocilizumab (TCZ) in combination with standard-of-care (SOC) in hospitalized adult participants with moderate to severe COVID-19 pneumonia.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TCZ 8 mg/kg | Active Comparator | Participants will receive intravenous (IV) tocilizumab (TCZ) at a dose of 8 mg/kg in addition to standard-of-care treatment. |
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| TCZ 4 mg/kg | Experimental | Participants will receive IV tocilizumab (TCZ) at a dose of 4 mg/kg in addition to standard-of-care treatment. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tociliuzumab | Drug | Participants will receive IV TCZ. |
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| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Curve From Day 0-28 (AUC0-d28) of Tocilizumab) | 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. | |
| Maximum Serum Concentration (Cmax) of Tocilizumab | 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. | |
| Clearance (CL) of Tocilizumab | 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. | |
| Volume of the Central Compartment (Vc) of Tocilizumab | 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. | |
| Serum Concentration of C-reactive Protein (CRP) Following Administration of IV TCZ | Baseline - Day 60 | |
| Serum Concentration of Ferritin Following Administration of IV TCZ | Baseline - Day 60 | |
| Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R) Following Administration of IV TCZ | Baseline - Day 60 | |
| Serum Concentration of Interleukin-6 (IL-6) Following Administration of IV TCZ |
| Measure | Description | Time Frame |
|---|---|---|
| Pecentage of Participants With Adverse Events | 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. |
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Inclusion Criteria
Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic - Arizona | Phoenix | Arizona | 85054 | United States | ||
| St. Jude Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35024375 | Derived | Kumar PN, Hernandez-Sanchez J, Nagel S, Feng Y, Cai F, Rabin J, Morse CG, Nadig NR, Ashraf O, Gotur DB, McComsey GA, Gafoor K, Perin P, Thornton SC, Stubbings W, Lin CJF, Tsai L. Safety and Efficacy of Tocilizumab 4 or 8 mg/kg in Hospitalized Patients With Moderate to Severe Coronavirus Disease 2019 Pneumonia: A Randomized Clinical Trial. Open Forum Infect Dis. 2021 Dec 4;9(1):ofab608. doi: 10.1093/ofid/ofab608. eCollection 2022 Jan. | |
| 34612846 |
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Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).
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| ID | Title | Description |
|---|---|---|
| FG000 | TCZ 4 mg/kg | Participants received intravenous (IV) tocilizumab (TCZ) at a dose of 4 mg/kg in addition to standard-of-care treatment. |
| FG001 | TCZ 8 mg/kg | Participants received IV tocilizumab (TCZ) at a dose of 8 mg/kg in addition to standard-of-care treatment. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 15, 2020 | Jul 30, 2021 |
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| Baseline - Day 60 |
| Up to Day 60 |
| Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) (COVID-19) Viral Load Over Time | Baseline - Day 60 |
| Time to Real-Time Polymerase Chain Reaction (RT-PCR) Virus Negativity | 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. | Up to Day 28 |
| Proportion of Participants With Any Post-Treatment Infection | Up to Day 60 |
| Fullerton |
| California |
| 92835 |
| United States |
| LAC + USC Medical Center | Los Angeles | California | 90033 | United States |
| USC Keck Medical Center of USC | Los Angeles | California | 90033 | United States |
| Norwalk Hospital | Norwalk | Connecticut | 06856 | United States |
| Medstar Georgetown University Hospital | Washington D.C. | District of Columbia | 20007 | United States |
| Mayo Clinic | Jacksonville | Florida | 32224 | United States |
| Advocate Christ Medical Center | Oak Lawn | Illinois | 60453 | United States |
| Advocate Lutheran General Hospital | Park Ridge | Illinois | 60068 | United States |
| University of Maryland | Baltimore | Maryland | 21201 | United States |
| Renown Institute for Heart & Vascular Health | Reno | Nevada | 89502 | United States |
| St Joseph's Regional Medical Center | Wayne | New Jersey | 07470 | United States |
| SUNY Downstate Medical Center. | Brooklyn | New York | 11203 | United States |
| Jamaica Hospital Medical Center | Jamaica | New York | 11418 | United States |
| Wake Forest University Health Sciences | Winston-Salem | North Carolina | 27157 | United States |
| University Hospitals Cleveland Medical Center | Cleveland | Ohio | 44106 | United States |
| Mercy St. Vincent Medical Center | Toledo | Ohio | 43608 | United States |
| Lehigh Valley Health Network | Allentown | Pennsylvania | 18103 | United States |
| Temple University Hospital | Philadelphia | Pennsylvania | 19140 | United States |
| Allegheny Health Network (Pittsburg PA) | Pittsburgh | Pennsylvania | 15212 | United States |
| Medical University of South Carolina | Charleston | South Carolina | 29425 | United States |
| Houston Methodist Hospital | Houston | Texas | 77030 | United States |
| Michael E. DeBakey VA Medical Center | Houston | Texas | 77030 | United States |
| Houston Methodist Sugar Land Hospital | Sugar Land | Texas | 77479 | United States |
| Derived |
| Tom J, Bao M, Tsai L, Qamra A, Summers D, Carrasco-Triguero M, McBride J, Rosenberger CM, Lin CJF, Stubbings W, Blyth KG, Carratala J, Francois B, Benfield T, Haslem D, Bonfanti P, van der Leest CH, Rohatgi N, Wiese L, Luyt CE, Kheradmand F, Rosas IO, Cai F. Prognostic and Predictive Biomarkers in Patients With Coronavirus Disease 2019 Treated With Tocilizumab in a Randomized Controlled Trial. Crit Care Med. 2022 Mar 1;50(3):398-409. doi: 10.1097/CCM.0000000000005229. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | TCZ 4 mg/kg | Participants received intravenous (IV) tocilizumab (TCZ) at a dose of 4 mg/kg in addition to standard-of-care treatment. |
| BG001 | TCZ 8 mg/kg | Participants received IV tocilizumab (TCZ) at a dose of 8 mg/kg in addition to standard-of-care treatment. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Curve From Day 0-28 (AUC0-d28) of Tocilizumab) | 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. | Posted | Median | Full Range | µg/mL*day | 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. |
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| Primary | Maximum Serum Concentration (Cmax) of Tocilizumab | 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. | Posted | Median | Full Range | µg/mL | 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. |
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| Primary | Clearance (CL) of Tocilizumab | 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. | Posted | Median | Full Range | L/day | 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. |
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| Primary | Volume of the Central Compartment (Vc) of Tocilizumab | 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. | Posted | Median | Full Range | L | 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. |
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| Primary | Serum Concentration of C-reactive Protein (CRP) Following Administration of IV TCZ | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | mg/L | Baseline - Day 60 |
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| Primary | Serum Concentration of Ferritin Following Administration of IV TCZ | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | pmol/L | Baseline - Day 60 |
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| Primary | Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R) Following Administration of IV TCZ | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/L | Baseline - Day 60 |
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| Primary | Serum Concentration of Interleukin-6 (IL-6) Following Administration of IV TCZ | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/L | Baseline - Day 60 |
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| Secondary | Pecentage of Participants With Adverse Events | 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. | The safety population included all randomized participants who received any amount of study drug, with participants analyzed according to the treatment received. | Posted | Number | Percentage of Participants | Up to Day 60 |
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| Secondary | Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) (COVID-19) Viral Load Over Time | The safety population included all randomized participants who received any amount of study drug, with participants analyzed according to the treatment received. | Posted | Median | Full Range | copies/µL | Baseline - Day 60 |
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| Secondary | Time to Real-Time Polymerase Chain Reaction (RT-PCR) Virus Negativity | 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. | Only participants with at least one virology assessment were included in the analysis. | Posted | Number | Probability | Up to Day 28 |
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| Secondary | Proportion of Participants With Any Post-Treatment Infection | Posted | Number | Percentage of Participants | Up to Day 60 |
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Up to Day 60
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | TCZ 4 mg/kg | Participants received intravenous (IV) tocilizumab (TCZ) at a dose of 4 mg/kg in addition to standard-of-care treatment. | 8 | 49 | 15 | 49 | 4 | 49 |
| EG001 | TCZ 8 mg/kg | Participants received IV tocilizumab (TCZ) at a dose of 8 mg/kg in addition to standard-of-care treatment. | 6 | 48 | 12 | 48 | 3 | 48 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Disseminated intravascular coagulation | Blood and lymphatic system disorders | MedDRA v23.0 | Non-systematic Assessment |
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| Cardiac failure congestive | Cardiac disorders | MedDRA v23.0 | Non-systematic Assessment |
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| Cardiogenic shock | Cardiac disorders | MedDRA v23.0 | Non-systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA v23.0 | Non-systematic Assessment |
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| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA v23.0 | Non-systematic Assessment |
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| Multiple organ dysfunction syndrome | General disorders | MedDRA v23.0 | Non-systematic Assessment |
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| Cholecystitis acute | Hepatobiliary disorders | MedDRA v23.0 | Non-systematic Assessment |
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| Drug-induced liver injury | Hepatobiliary disorders | MedDRA v23.0 | Non-systematic Assessment |
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| Atypical pneumonia | Infections and infestations | MedDRA v23.0 | Non-systematic Assessment |
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| COVID-19 pneumonia | Infections and infestations | MedDRA v23.0 | Non-systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA v23.0 | Non-systematic Assessment |
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| Sepsis | Infections and infestations | MedDRA v23.0 | Non-systematic Assessment |
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| Septic shock | Infections and infestations | MedDRA v23.0 | Non-systematic Assessment |
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| Staphylococcal infection | Infections and infestations | MedDRA v23.0 | Non-systematic Assessment |
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| Sputum culture positive | Investigations | MedDRA v23.0 | Non-systematic Assessment |
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| Failure to thrive | Metabolism and nutrition disorders | MedDRA v23.0 | Non-systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | MedDRA v23.0 | Non-systematic Assessment |
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| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA v23.0 | Non-systematic Assessment |
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| Cerebral infarction | Nervous system disorders | MedDRA v23.0 | Non-systematic Assessment |
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| Intensive care unit acquired weakness | Nervous system disorders | MedDRA v23.0 | Non-systematic Assessment |
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| Mental status changes | Psychiatric disorders | MedDRA v23.0 | Non-systematic Assessment |
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| Acute kidney injury | Renal and urinary disorders | MedDRA v23.0 | Non-systematic Assessment |
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| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
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| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
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| Aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
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| Hydrothorax | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
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| Mediastinal haematoma | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
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| Pneumomediastinum | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
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| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
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| Respiratory acidosis | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
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| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
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| Subcutaneous emphysema | Skin and subcutaneous tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA v23.0 | Non-systematic Assessment |
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| Shock | Vascular disorders | MedDRA v23.0 | Non-systematic Assessment |
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| Shock haemorrhagic | Vascular disorders | MedDRA v23.0 | Non-systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Alanine aminotransferase increased | Investigations | MedDRA v23.0 | Non-systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA v23.0 | Non-systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | MedDRA v23.0 | Non-systematic Assessment |
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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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-La Roche | 1-800-821-8590 | genentech@druginfo.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 1, 2020 | Jul 30, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| C502936 | tocilizumab |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Two doses |
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