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Clinical Trial to Evaluate the Effectiveness and Safety of Tocilizumab for Treating Patients With COVID-19 Pneumonia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04445272
Recruitment Status : Recruiting
First Posted : June 24, 2020
Last Update Posted : June 24, 2020
Sponsor:
Collaborators:
Roche Pharma AG
Dynamic Science S.L.
Information provided by (Responsible Party):
Fundacion SEIMC-GESIDA

Brief Summary:

At present, no treatment has been approved for COVID-19. However, in light of the increased interest on using the anti-cytokine therapy targeting IL-6 tocilizumab in COVID-19 infected patients due to its potential benefit, the Spanish Agency for Medicine and Health Products (Agencia Española de Medicamentos y Productos Sanitarios, AEMPS) have initiated the controlled distribution of the drug. Tocilizumab is indeed proposed as a potential treatment for severe COVID-19 in Spain. Based on the positive results of tocilizumab in the treatment of COVID-19 patients and the experience of tocilizumab in inducing rapid reversal of CSS in other pathologies several clinical trials and observational studies are being conducted to assess the effectiveness and safety of tocilizumab in COVID-19 patients. Further studies with a large sample size are required to confirm the effectiveness of tocilizumab in patients with COVID-19 pneumonia.

The need for the management of severe COVID-19 disease is imperative, and every effort should be made to collect relevant clinical outcomes. The aim of the present study is to evaluate the effectiveness of IV tocilizumab in treating patients with COVID-19 pneumonia who are currently hospitalized or admitted to ICU by describing improvement of respiratory function and mortality rate. This large real-world cohort therefore provides a unique opportunity to study this potential medicine during the current emergency situation, and support the findings from other ongoing clinical trials and observational studies, such as the Roche-sponsored Phase III study that is planned to start early April.


Condition or disease Intervention/treatment Phase
COVID-19 Drug: Tocilizumab Phase 2

Detailed Description:

Cytokine storm syndrome (CSS) is caused by the excessive release of cytokines during an exaggerated immune response. CSS can be triggered by infections or therapeutic interventions, being more severe depending on the degree and duration of immune activation. CSS is as a significant on-target side-effect of chimeric antigen receptor (CAR) T-cell therapies, which have been subject to assessment for the treatment of haematological malignancies. Tocilizumab (intravenous, IV) is indicated for the treatment of chimeric antigen receptor CAR T cell-induced severe or life-threatening CSS.

Based on the experience with tocilizumab in the CSS, and that some patients infected with SARS-CoV-2 can develop CSS, leading to potentially fatal damage to lung tissue, the drug is being investigated in China and Italy, and clinical trials are being conducted/planned in these and several other countries. Real-word experience with tocilizumab IV have shown that in a substantial proportion of COVID-19 patients with severe pneumonia, fever returned to normal and respiratory function based on oxygen intake and lung opacities improved remarkably. Laboratory parameters such as C-reactive protein (CRP) that seem to be increased in patients infected decreased significantly with tocilizumab, and lymphocytes levels also returned to normal.

All these findings have led the Spanish Agency for Medicine and Health Products (AEMPS) to initiate the controlled distribution of tocilizumab IV, in light of the increased interest on the anti-cytokine therapy targeting IL-6 in COVID-19 infected patients. Therefore, tocilizumab might be among the therapeutic armamentarium for preventing the fatal consequences of acute respiratory and multi organ failure in around 20% of the COVID-19 infected patients.

The aim of the present study is to evaluate the effectiveness and safety of IV tocilizumab in patients with COVID-19 severe pneumonia who are currently hospitalized or admitted to ICU. This large real-world cohort provides a unique opportunity to study a potential medicine during the current emergency situation, and support the findings from the Roche-sponsored Phase III study that is planned to start in early April.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 500 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Phase II, one-arm, open label, multicentre study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicentre, Open-label Clinical Trial to Evaluate the Effectiveness and Safety of Intravenous Tocilizumab for Treating Patients With COVID-19 Pneumonia: the BREATH-19 Study
Actual Study Start Date : May 22, 2020
Estimated Primary Completion Date : August 22, 2020
Estimated Study Completion Date : August 22, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pneumonia
Drug Information available for: Tocilizumab

Arm Intervention/treatment
Experimental: Tocilizumab

Patients will receive IV tocilizumab as per clinical practice and at the discretion of treating investigator, following the posology indicated in the SmPC, or the recommendations proposed by the Spanish Ministry of Health:

The recommended posology by the SmPC is 8 mg per kg in patients weighing greater than or equal to 30 kg or 12 mg per kg in patients weighing less than 30 kg. If no clinical improvement in the signs and symptoms up to 3 additional doses of tocilizumab may be administered. The interval between consecutive doses should be at least 8 hours.

The recommendations of the Spanish Ministry of Health:

Patients more than 80 kg: first dose 600 mg; second dose 600 mg. Patients less than 80 kg: first dose 600 mg; second dose 400 mg.

A third dose might be considered 16 to 24 hours after if: fever persists or a worsening of the laboratory parameters

Given the exceptionality of the situation modification of doses according to the physician experience will be allowed.

Drug: Tocilizumab
Treatment with Tocilizumab




Primary Outcome Measures :
  1. To calulate the time of intubation [ Time Frame: through study completion, and average of 1 month ]
    Calculate the mean time of intubation

  2. To calculate the time with oxygen therapy [ Time Frame: through study completion, and average of 1 month ]
    Calculate the mean time with oxygen therapy

  3. To calculate the time with Non-invasive mechanical ventilation [ Time Frame: through study completion, and average of 1 month ]
    Calculate the mean time with Non-invasive mechanical ventilation

  4. To evaluate mortality rate [ Time Frame: through study completion, and average of 1 month ]
    Number of patients deaths of the total of patients included


Secondary Outcome Measures :
  1. To calculate respiratory function parameters [ Time Frame: through study completion, and average of 1 month ]
    To calculate the mean ofPaO2/FiO2

  2. To calculate respiratory function parameters [ Time Frame: through study completion, and average of 1 month ]
    To calculate the mean of levels of oxygen saturation

  3. To calculate respiratory function parameters [ Time Frame: through study completion, and average of 1 month ]
    To calculate the mean of SaO2/FiO2

  4. To evaluate radiological lung extension [ Time Frame: through study completion, and average of 1 month ]
    Evaluate the lung extension of pneumonia

  5. To evaluate radiological evolution [ Time Frame: through study completion, and average of 1 month ]
    Evaluate the type of lung affection

  6. To describe the duration of hospitalization and ICU use [ Time Frame: through study completion, and average of 1 month ]
    Days of hospitalization in survivors and/or days at ICU throughout the study

  7. To evaluate the requirement of additional organ support [ Time Frame: through study completion, and average of 1 month ]
    Percentage of patients with extracorporeal membrane oxygenation

  8. To evaluate the requirement of additional organ support [ Time Frame: through study completion, and average of 1 month ]
    Percentage of patients with molecular adsorbent recirculating system

  9. To evaluate the requirement of additional organ support [ Time Frame: through study completion, and average of 1 month ]
    Percentage of patients with dialysis

  10. To evaluate the requirement of additional organ support [ Time Frame: through study completion, and average of 1 month ]
    Percentage of patients with other support therapy

  11. To evaluate the effect of IV tocilizumab on the serum levels of inflammatory markers [ Time Frame: through study completion, and average of 1 month ]
    Analyze the levels of IL-6

  12. To calculate the number of adverse events in patients with COVID-19 pneumonia treated with Tocilizumab [ Time Frame: through study completion, and average of 1 month ]
    Incidence of adverse events

  13. To calculate the number of adverse events in patients with COVID-19 pneumonia treated with Tocilizumab [ Time Frame: through study completion, and average of 1 month ]
    Incidence of adverse events by dose of Tocilizumab

  14. To assess time to reverse-transcriptase polymerase chain reaction (RT-PCR) virus negativity [ Time Frame: through study completion, and average of 1 month ]
    To evaluate the time to RT-PCR virus negativity

  15. To evaluate the effect of IV tocilizumab on the serum levels of inflammatory [ Time Frame: through study completion, and average of 1 month ]
    Analyze the levels of CRP

  16. To evaluate the effect of IV tocilizumab on the serum levels of inflammatory [ Time Frame: through study completion, and average of 1 month ]
    Analyze the levels of procalcitonin (PCT)

  17. To evaluate the effect of IV tocilizumab on the serum levels of inflammatory [ Time Frame: through study completion, and average of 1 month ]
    Analyze the levels of ID-dimer

  18. To evaluate the effect of IV tocilizumab on the serum levels of inflammatory [ Time Frame: through study completion, and average of 1 month ]
    Analyze the levels of ferritin

  19. To calculate the number of serious adverse events in patients with COVID-19 pneumonia treated with Tocilizumab [ Time Frame: through study completion, and average of 1 month ]
    Indicende of serious adverse events

  20. To calculate the number of serious adverse events in patients with COVID-19 pneumonia treated with Tocilizumab [ Time Frame: through study completion, and average of 1 month ]
    Indicende of serious adverse events based on dose of Tocilizumab

  21. To calculate the number of adverse events of special interest in patients with COVID-19 pneumonia treated with Tocilizumab [ Time Frame: through study completion, and average of 1 month ]
    Indicende of adverse events of special interest based on dose of Tocilizumab

  22. To evaluate mortality rate [ Time Frame: through study completion, and average of 1 month ]
    Number of patients deaths of the total of patients included based on dose of Tocilizumab

  23. To evaluate respiratory function [ Time Frame: through study completion, and average of 1 month ]
    Time with intubation, oxygen therapy and Non-invasive mechanical ventilation based on dose of Tocilizumab

  24. To evaluate mortality rate [ Time Frame: through study completion, and average of 1 month ]
    Number of patients deaths of the total of patients included based on severity of disease at the start of the study treatment

  25. To evaluate mortality rate [ Time Frame: through study completion, and average of 1 month ]
    Number of patients deaths of the total of patients included based on presence of cytokine storm syndrome at the start of treatment

  26. To evaluate respiratory function [ Time Frame: through study completion, and average of 1 month ]
    Time with intubation, oxygen therapy and Non-invasive mechanical ventilation based on severity of disease at the start of the study treatment

  27. To evaluate respiratory function [ Time Frame: through study completion, and average of 1 month ]
    Time with intubation, oxygen therapy and Non-invasive mechanical ventilation based on presence of cytokine storm syndrome at the start of treatment



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Provide oral informed consent to participate in this study.
  • At least 18 years of age.
  • Diagnosed with COVID-19 pneumonia by RT-PCR.
  • Have received the first dose of tocilizumab a maximum of two days before the inclusion or is candidate for tocilizumab treatment
  • Hospitalized or admitted to ICU

Exclusion Criteria:

  • The patient has any other medical condition or is receiving concomitant medication that could, in the opinion of the investigator, compromise the patient's safety or collected data
  • Known severe allergic reactions to tocilizumab or other monoclonal antibodies
  • Active acute and severe infections, including tuberculosis infection
  • Pregnant or breastfeeding, or positive pregnancy test in a pre-dose examination

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04445272


Contacts
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Contact: Raul Montalban Casado +34 639067369 raul.m@dynasolutions.com
Contact: María Yllescas Ruiz +34 915568025 myllescas@f-sg.org

Locations
Show Show 47 study locations
Sponsors and Collaborators
Fundacion SEIMC-GESIDA
Roche Pharma AG
Dynamic Science S.L.
Investigators
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Principal Investigator: Jose Antonio Pérez Molina Hospital Universitario Ramón y Cajal
Publications:
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Responsible Party: Fundacion SEIMC-GESIDA
ClinicalTrials.gov Identifier: NCT04445272    
Other Study ID Numbers: BREATH-19 (FSG011-20)
First Posted: June 24, 2020    Key Record Dates
Last Update Posted: June 24, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Fundacion SEIMC-GESIDA:
COVID-19
Additional relevant MeSH terms:
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Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections