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

Phase 2

Terminated

• Conditions: Covid19
• Interventions: Drug: Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA]_#1; Drug: Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA]_#1 (2 doses)

• Registration Number: NCT04435717
• Lead Sponsor: Hospital Universitario Ramon y Cajal

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study Start: 2020-05-04
• Study First Submitted: 2020-06-11
• Study First Submitted QC: 2020-06-16
• Study First Posted: 2020-06-17
• Primary Completion: 2020-11-04
• Study Completion: 2021-02-10
• Status Verified: 2021-08
• Last Update Submitted: 2021-08-24
• Last Update Posted: 2021-08-30

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 26

Inclusion Criteria

1. 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.

2. 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

3. The patient is hospitalized or meets hospital admission criteria.

4. The patient is not expected to enter the ICU or die in the next 24 hours.

Exclusion Criteria

1. Participants in another simultaneous clinical trial.
2. Use of other immunomodulators.
3. Coinfection with the hepatitis B virus (detectable AgSup-HBV).
4. Pregnancy (or planning to become pregnant during the course of the study), or lactation period.
5. Presence of laboratory abnormalities of grade ≥ 4.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TCZ 8 mg / kg one dose	Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA]_#1	TCZ 8 mg / kg (with a maximum of 800 mg) in single dose + usual treatment
TCZ 8 mg / kg in two	Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA]_#1 (2 doses)	TCZ 8 mg / kg in two doses at 0 and 12 hours (with a maximum of 800 mg per dose) + usual treatment

Primary Outcome Measures

Name	Time	Method
Change 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.	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Hospital Universitario Ramón y Cajal; 🇪🇸 Madrid, Spain