Efficacy of Tocilizumab in Modifying the Inflammatory Parameters of Patients With COVID-19 (COVITOZ-01)

Study Overview
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Brief Summary
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unicenter, randomized, open-label clinical trial on the efficacy of tocilizumab in modifying the inflammatory parameters of patients with COVID-19.

Detailed Description
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National, unicenter, randomized, open-label, controlled phase II clinical trial with a drug marketed and administered under conditions of use other than those approved. The study is designed to evaluate the effect of adding Tocilizumab to standard or standard of care for patients infected with COVID-19 and diagnosed with mild-moderate pneumonia. 78 patients are expected to be included in the study in a single center in Spain. The study includes a selection and randomization period, and a 28-day follow-up period (or until death, or premature withdrawal, whichever is earlier). Once the patients complete the study, they will continue with their usual follow-up.

Official Title
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Unicenter, Randomized, Open-label Clinical Trial on the Efficacy of Tocilizumab in Modifying the Inflammatory Parameters of Patients With COVID-19

Conditions
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Covid19

Intervention / Treatment
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* Drug: Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA]_#1
* Drug: Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA]_#1 (2 doses)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients over 18 years of age who have given their informed consent. This will be collected verbally and will be recorded in the medical record by the investigating doctor. The patient is diagnosed with mild-moderate SARS-CoV-2 pneumonia confirmed microbiologically ≤7 days before randomization, and presents: to. Basal oxygen saturation> 90% b. CURB-65 ≤1 c. PaO2 / FiO2≥300 or SatO2 / FiO2≥315 The patient is hospitalized or meets hospital admission criteria. The patient is not expected to enter the ICU or die in the next 24 hours. Exclusion Criteria: Participants in another simultaneous clinical trial. Use of other immunomodulators. Coinfection with the hepatitis B virus (detectable AgSup-HBV). Pregnancy (or planning to become pregnant during the course of the study), or lactation period. Presence of laboratory abnormalities of grade ≥ 4.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Patients eligible to be included in the study will be randomized in a 1: 1: 1 ratio to receive: TCZ 8 mg / kg (with a maximum of 800 mg) in single dose + usual treatment TCZ 8 mg / kg in two doses at 0 and 12 hours (with a maximum of 800 mg per dose) + usual treatment Usual / standard care treatment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TCZ 8 mg / kg one dose<br>TCZ 8 mg / kg (with a maximum of 800 mg) in single dose + usual treatment | Drug: Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA]_#1<br>* Tocilizumab 20 MG/ML Intravenous (one dose)<br>|
| Experimental: TCZ 8 mg / kg in two<br>TCZ 8 mg / kg in two doses at 0 and 12 hours (with a maximum of 800 mg per dose) + usual treatment | Drug: Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA]_#1 (2 doses)<br>* Tocilizumab 20 MG/ML Intravenous ( two doses)<br>* Other names: Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA]_#1;|
| No Intervention: standard care treatment<br>Usual / standard care treatment | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in IL-12 values in the 3 study groups from the start of treatment (D0) and on days D + 1 and D + 3. | Average increase in IL-12 values in the 3 study groups from the start of treatment (D0) and on days D + 1 and D + 3. | Day1 and Day3. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression of pneumonia | Percentage of patients per group with progression of pneumonia in Day3, Day 7 and Day28 | Day3, Day7 and Day28 | 
| PaO2/FiO2 | Proportion of patients with PaO2 / FiO2 <300 (or SatO2 / FiO2 ≤315) at some point in the evolution. | Day3, Day7 and Day28 | 
| cause mortality to 28 days after started treatment | cause mortality to 28 days after started treatment | Day3, Day7 and Day28 | 
| Length of hospital stay | Length of hospital stay | Day3, Day7 and Day28 | 
| patients requiring Intensive Care Unit admission | Percentage of patients requiring Intensive Care Unit admission | Day3, Day7 and Day28 | 
| evolution of inflammatory parameters IL12 | IL-12 levels at Day 7 | Day0, Day3 and Day7 | 
| evolution of inflammatory parameters IL-10, IL-1, IL-6, IL-17 and IFN-gamma | IL-10, IL-1, IL-6, IL-17 and IFN-gamma levels on days Day 0, Day1, Day 3 and Day 7 | Day0, Day3 and Day7 | 
| evolution of inflammatory parameters Procalcitonin (PCT), | Procalcitonin (PCT), levels on days Day0, Day1, Day3 and Day 7 7 | Day0, Day3 and Day7 | 
| evolution of inflammatory parameters C-reactive protein (PCR), | C-reactive protein (PCR),levels on days Day0, Day1, Day3 and Day 7 7 | Day0, Day3 and Day7 | 
| evolution of inflammatory parameters D-dimer | D-dimer levels on days Day0, Day1, Day3 and Day 7 7 | Day0, Day3 and Day7 | 
| evolution of inflammatory parameters and ferritin | ferritin levels on days Day0, Day1, Day3 and Day 7 7 | Day0, Day3 and Day7 | 
| pharmacokinetics of tocilizumab Cmin | Cmin,on Day0, Day1, Day3 and Day7. On day 0 (D0), blood samples will be collected 12 hours after the infusion of each dose of tocilizumab in both experimental treatment groups. | Day0, Day1 Day3 and Day7 | 
| pharmacokinetics of tocilizumab Cmax | Cmax,on Day0, Day1, Day3 and Day7. On day 0 (D0), blood samples will be collected 12 hours after the infusion of each dose of tocilizumab in both experimental treatment groups. | days Day0, Day1 Day3 and Day7 | 
| pharmacokinetics of tocilizumab Cmedia | Cmedia,on Day0, Day1, Day3 and Day7. On day 0 (D0), blood samples will be collected 12 hours after the infusion of each dose of tocilizumab in both experimental treatment groups. | days Day0, Day1 Day3 and Day7 | 
| pharmacokinetics of tocilizumab Tmax | Tmax,on Day0, Day1, Day3 and Day7. On day 0 (D0), blood samples will be collected 12 hours after the infusion of each dose of tocilizumab in both experimental treatment groups. | days Day0, Day1 Day3 and Day7 | 
| pharmacokinetics of tocilizumab AUC | AUC,on Day0, Day1, Day3 and Day7. On day 0 (D0), blood samples will be collected 12 hours after the infusion of each dose of tocilizumab in both experimental treatment groups. | days Day0, Day1 Day3 and Day7 | 
| Adverse event | Serious and non-serious adverse events. | days Day0, Day3, Day7 and Day28 | 
| Adverse event to cause the treatment interruption. | Adverse events to cause the treatment interruption. | days Day0, Day3, Day7 and Day28 | 
| Adverse event Abnormalities in laboratory | Abnormalities in laboratory findings unrelated to COVID-19 disease. | days Day0, Day3, Day7 and Day28 |