<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04435717</url>
  </required_header>
  <id_info>
    <org_study_id>COVITOZ-01</org_study_id>
    <nct_id>NCT04435717</nct_id>
  </id_info>
  <brief_title>Efficacy of Tocilizumab in Modifying the Inflammatory Parameters of Patients With COVID-19 (COVITOZ-01)</brief_title>
  <acronym>COVITOZ-01</acronym>
  <official_title>Unicenter, Randomized, Open-label Clinical Trial on the Efficacy of Tocilizumab in Modifying the Inflammatory Parameters of Patients With COVID-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital Universitario Ramon y Cajal</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospital Universitario Ramon y Cajal</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      unicenter, randomized, open-label clinical trial on the efficacy of tocilizumab in modifying&#xD;
      the inflammatory parameters of patients with COVID-19.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      National, unicenter, randomized, open-label, controlled phase II clinical trial with a drug&#xD;
      marketed and administered under conditions of use other than those approved.&#xD;
&#xD;
      The study is designed to evaluate the effect of adding Tocilizumab to standard or standard of&#xD;
      care for patients infected with COVID-19 and diagnosed with mild-moderate pneumonia.&#xD;
&#xD;
      78 patients are expected to be included in the study in a single center in Spain. The study&#xD;
      includes a selection and randomization period, and a 28-day follow-up period (or until death,&#xD;
      or premature withdrawal, whichever is earlier). Once the patients complete the study, they&#xD;
      will continue with their usual follow-up.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Futility&#xD;
  </why_stopped>
  <start_date type="Actual">May 4, 2020</start_date>
  <completion_date type="Actual">February 10, 2021</completion_date>
  <primary_completion_date type="Actual">November 4, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Patients eligible to be included in the study will be randomized in a 1: 1: 1 ratio to receive:&#xD;
TCZ 8 mg / kg (with a maximum of 800 mg) in single dose + usual treatment&#xD;
TCZ 8 mg / kg in two doses at 0 and 12 hours (with a maximum of 800 mg per dose) + usual treatment&#xD;
Usual / standard care treatment</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in IL-12 values in the 3 study groups from the start of treatment (D0) and on days D + 1 and D + 3.</measure>
    <time_frame>Day1 and Day3.</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression of pneumonia</measure>
    <time_frame>Day3, Day7 and Day28</time_frame>
    <description>Percentage of patients per group with progression of pneumonia in Day3, Day 7 and Day28</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PaO2/FiO2</measure>
    <time_frame>Day3, Day7 and Day28</time_frame>
    <description>Proportion of patients with PaO2 / FiO2 &lt;300 (or SatO2 / FiO2 ≤315) at some point in the evolution.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>cause mortality to 28 days after started treatment</measure>
    <time_frame>Day3, Day7 and Day28</time_frame>
    <description>cause mortality to 28 days after started treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of hospital stay</measure>
    <time_frame>Day3, Day7 and Day28</time_frame>
    <description>Length of hospital stay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>patients requiring Intensive Care Unit admission</measure>
    <time_frame>Day3, Day7 and Day28</time_frame>
    <description>Percentage of patients requiring Intensive Care Unit admission</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>evolution of inflammatory parameters IL12</measure>
    <time_frame>Day0, Day3 and Day7</time_frame>
    <description>IL-12 levels at Day 7</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>evolution of inflammatory parameters IL-10, IL-1, IL-6, IL-17 and IFN-gamma</measure>
    <time_frame>Day0, Day3 and Day7</time_frame>
    <description>IL-10, IL-1, IL-6, IL-17 and IFN-gamma levels on days Day 0, Day1, Day 3 and Day 7</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>evolution of inflammatory parameters Procalcitonin (PCT),</measure>
    <time_frame>Day0, Day3 and Day7</time_frame>
    <description>Procalcitonin (PCT), levels on days Day0, Day1, Day3 and Day 7&#xD;
7</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>evolution of inflammatory parameters C-reactive protein (PCR),</measure>
    <time_frame>Day0, Day3 and Day7</time_frame>
    <description>C-reactive protein (PCR),levels on days Day0, Day1, Day3 and Day 7&#xD;
7</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>evolution of inflammatory parameters D-dimer</measure>
    <time_frame>Day0, Day3 and Day7</time_frame>
    <description>D-dimer levels on days Day0, Day1, Day3 and Day 7&#xD;
7</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>evolution of inflammatory parameters and ferritin</measure>
    <time_frame>Day0, Day3 and Day7</time_frame>
    <description>ferritin levels on days Day0, Day1, Day3 and Day 7&#xD;
7</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>pharmacokinetics of tocilizumab Cmin</measure>
    <time_frame>Day0, Day1 Day3 and Day7</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>pharmacokinetics of tocilizumab Cmax</measure>
    <time_frame>days Day0, Day1 Day3 and Day7</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>pharmacokinetics of tocilizumab Cmedia</measure>
    <time_frame>days Day0, Day1 Day3 and Day7</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>pharmacokinetics of tocilizumab Tmax</measure>
    <time_frame>days Day0, Day1 Day3 and Day7</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>pharmacokinetics of tocilizumab AUC</measure>
    <time_frame>days Day0, Day1 Day3 and Day7</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse event</measure>
    <time_frame>days Day0, Day3, Day7 and Day28</time_frame>
    <description>Serious and non-serious adverse events.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse event to cause the treatment interruption.</measure>
    <time_frame>days Day0, Day3, Day7 and Day28</time_frame>
    <description>Adverse events to cause the treatment interruption.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse event Abnormalities in laboratory</measure>
    <time_frame>days Day0, Day3, Day7 and Day28</time_frame>
    <description>Abnormalities in laboratory findings unrelated to COVID-19 disease.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Covid19</condition>
  <arm_group>
    <arm_group_label>TCZ 8 mg / kg one dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TCZ 8 mg / kg (with a maximum of 800 mg) in single dose + usual treatment</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TCZ 8 mg / kg in two</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TCZ 8 mg / kg in two doses at 0 and 12 hours (with a maximum of 800 mg per dose) + usual treatment</description>
  </arm_group>
  <arm_group>
    <arm_group_label>standard care treatment</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Usual / standard care treatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA]_#1</intervention_name>
    <description>Tocilizumab 20 MG/ML Intravenous (one dose)</description>
    <arm_group_label>TCZ 8 mg / kg one dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA]_#1 (2 doses)</intervention_name>
    <description>Tocilizumab 20 MG/ML Intravenous ( two doses)</description>
    <arm_group_label>TCZ 8 mg / kg in two</arm_group_label>
    <other_name>Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA]_#1</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients over 18 years of age who have given their informed consent. This will be&#xD;
             collected verbally and will be recorded in the medical record by the investigating&#xD;
             doctor.&#xD;
&#xD;
          2. The patient is diagnosed with mild-moderate SARS-CoV-2 pneumonia confirmed&#xD;
             microbiologically ≤7 days before randomization, and presents:&#xD;
&#xD;
             to. Basal oxygen saturation&gt; 90% b. CURB-65 ≤1 c. PaO2 / FiO2≥300 or SatO2 / FiO2≥315&#xD;
&#xD;
          3. The patient is hospitalized or meets hospital admission criteria.&#xD;
&#xD;
          4. The patient is not expected to enter the ICU or die in the next 24 hours.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Participants in another simultaneous clinical trial.&#xD;
&#xD;
          2. Use of other immunomodulators.&#xD;
&#xD;
          3. Coinfection with the hepatitis B virus (detectable AgSup-HBV).&#xD;
&#xD;
          4. Pregnancy (or planning to become pregnant during the course of the study), or&#xD;
             lactation period.&#xD;
&#xD;
          5. Presence of laboratory abnormalities of grade ≥ 4.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Hospital Universitario Ramón y Cajal</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>June 11, 2020</study_first_submitted>
  <study_first_submitted_qc>June 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 17, 2020</study_first_posted>
  <last_update_submitted>August 24, 2021</last_update_submitted>
  <last_update_submitted_qc>August 24, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 30, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hospital Universitario Ramon y Cajal</investigator_affiliation>
    <investigator_full_name>Jose A Perez Molina</investigator_full_name>
    <investigator_title>Sponsor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pharmaceutical Solutions</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04435717
org study id: COVITOZ-01
nct id: NCT04435717
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
unicenter, randomized, open-label clinical trial on the efficacy of tocilizumab in modifying
      the inflammatory parameters of patients with COVID-19.
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.
allocation: Randomized
intervention model: Single Group Assignment
intervention 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
primary purpose: Treatment
masking: None (Open Label)
measure: Change in IL-12 values in the 3 study groups from the start of treatment (D0) and on days D + 1 and D + 3.
time frame: Day1 and Day3.
description: 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.
measure: Progression of pneumonia
time frame: Day3, Day7 and Day28
description: Percentage of patients per group with progression of pneumonia in Day3, Day 7 and Day28
measure: PaO2/FiO2
time frame: Day3, Day7 and Day28
description: Proportion of patients with PaO2 / FiO2 <300 (or SatO2 / FiO2 ≤315) at some point in the evolution.
measure: cause mortality to 28 days after started treatment
time frame: Day3, Day7 and Day28
description: cause mortality to 28 days after started treatment
measure: Length of hospital stay
time frame: Day3, Day7 and Day28
description: Length of hospital stay
measure: patients requiring Intensive Care Unit admission
time frame: Day3, Day7 and Day28
description: Percentage of patients requiring Intensive Care Unit admission
measure: evolution of inflammatory parameters IL12
time frame: Day0, Day3 and Day7
description: IL-12 levels at Day 7
measure: evolution of inflammatory parameters IL-10, IL-1, IL-6, IL-17 and IFN-gamma
time frame: Day0, Day3 and Day7
description: IL-10, IL-1, IL-6, IL-17 and IFN-gamma levels on days Day 0, Day1, Day 3 and Day 7
measure: evolution of inflammatory parameters Procalcitonin (PCT),
time frame: Day0, Day3 and Day7
description: Procalcitonin (PCT), levels on days Day0, Day1, Day3 and Day 7
7
measure: evolution of inflammatory parameters C-reactive protein (PCR),
time frame: Day0, Day3 and Day7
description: C-reactive protein (PCR),levels on days Day0, Day1, Day3 and Day 7
7
measure: evolution of inflammatory parameters D-dimer
time frame: Day0, Day3 and Day7
description: D-dimer levels on days Day0, Day1, Day3 and Day 7
7
measure: evolution of inflammatory parameters and ferritin
time frame: Day0, Day3 and Day7
description: ferritin levels on days Day0, Day1, Day3 and Day 7
7
measure: pharmacokinetics of tocilizumab Cmin
time frame: Day0, Day1 Day3 and Day7
description: 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.
measure: pharmacokinetics of tocilizumab Cmax
time frame: days Day0, Day1 Day3 and Day7
description: 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.
measure: pharmacokinetics of tocilizumab Cmedia
time frame: days Day0, Day1 Day3 and Day7
description: 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.
measure: pharmacokinetics of tocilizumab Tmax
time frame: days Day0, Day1 Day3 and Day7
description: 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.
measure: pharmacokinetics of tocilizumab AUC
time frame: days Day0, Day1 Day3 and Day7
description: 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.
measure: Adverse event
time frame: days Day0, Day3, Day7 and Day28
description: Serious and non-serious adverse events.
measure: Adverse event to cause the treatment interruption.
time frame: days Day0, Day3, Day7 and Day28
description: Adverse events to cause the treatment interruption.
measure: Adverse event Abnormalities in laboratory
time frame: days Day0, Day3, Day7 and Day28
description: Abnormalities in laboratory findings unrelated to COVID-19 disease.
arm group label: TCZ 8 mg / kg one dose
arm group type: Experimental
description: TCZ 8 mg / kg (with a maximum of 800 mg) in single dose + usual treatment
arm group label: TCZ 8 mg / kg in two
arm group type: Experimental
description: TCZ 8 mg / kg in two doses at 0 and 12 hours (with a maximum of 800 mg per dose) + usual treatment
arm group label: standard care treatment
arm group type: No Intervention
description: Usual / standard care treatment
intervention type: Drug
intervention name: Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA]_#1
description: Tocilizumab 20 MG/ML Intravenous (one dose)
arm group label: TCZ 8 mg / kg one dose
intervention type: Drug
intervention name: Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA]_#1 (2 doses)
description: Tocilizumab 20 MG/ML Intravenous ( two doses)
arm group label: TCZ 8 mg / kg in two
other name: Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA]_#1
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Spain
responsible party type: Principal Investigator
investigator affiliation: Hospital Universitario Ramon y Cajal
investigator full name: Jose A Perez Molina
investigator title: Sponsor
mesh term: COVID-19
mesh term: Pharmaceutical Solutions
sharing ipd: No