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

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

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

Study Overview

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

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 Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28034
    • Hospital Universitario Ramón y Cajal

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TCZ 8 mg / kg one dose; TCZ 8 mg / kg (with a maximum of 800 mg) in single dose + usual treatment	Drug: Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA]_#1; Tocilizumab 20 MG/ML Intravenous (one dose)
Experimental: TCZ 8 mg / kg in two; 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); Tocilizumab 20 MG/ML Intravenous ( two doses); Other Names: Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA]_#1
No Intervention: standard care treatment; Usual / standard care treatment

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hospital Universitario Ramon y Cajal

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2020
• Primary Completion (Actual): November 4, 2020
• Study Completion (Actual): February 10, 2021

Study Registration Dates

• First Submitted: June 11, 2020
• First Submitted That Met QC Criteria: June 16, 2020
• First Posted (Actual): June 17, 2020

Study Record Updates

• Last Update Posted (Actual): August 30, 2021
• Last Update Submitted That Met QC Criteria: August 24, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Pharmaceutical Solutions
• Other Study ID Numbers: COVITOZ-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No