- Pneumonia is the most frequent and serious complication of coronavirus infection.
- IL-6 is one of the mediators of inflammation that follows the immune response against the virus in the lung alveolus. The «cytokine storm» produces significant damage to the lung parenchyma with interstitial disease that significantly reduces respiratory function.
- Tocilizumab, a humanized recombinant monoclonal antibody directed against the IL-6 provided clinical benefits and changes in biomarkers in a case study on 21 Chinese patients with severe COVID-19 pneumonia (Xiaoling X. et al).
- The Italian Medicines Agency (AIFA) announced on March 19 the launch of TOCIVID-19, an independent phase 2 study to evaluate the efficacy and safety of tocilizumab in the treatment of pneumonia during COVID-19.
- The trial has two main goals: to produce good quality data from a methodological point of view and to track all the off-label treatments with tocilizumab already going on, to evaluate systematically their impact on mortality.
- Single-arm study including two different groups of patients treated with the same protocol.
- The first group (phase 2 study) will test the hypothesis of one-month mortality reduction and will include 330 patients hospitalized for COVID-19 pneumonia with first signs of respiratory failure or who are intubated since less than 24 hours.
- The second group (data collection or observational study) has the aim to improve the procedures for managing the ongoing emergency and will include patients who are intubated since more than 24 hours and patients who have already been treated before the starting of the trial, both in intubated or not. The numerosity of this group will be determined both by the results of the phase 2 arm and the trend of the pandemic.
- Data will be collected using an online platform for clinical trials developed for oncological trials.
- Dosage: tocilizumab i.v. 8 mg/kg up to a maximum of 800 mg per dose (the dosage allowed by the FDA for the treatment of the "cytokine storm" following treatment with CAR-T cells).
- A second dose can be administered after 12 hours if respiratory function is not restored.
- No age limit.
- Positive real-time PCR for SARS-CoV2.
- Oxygen saturation ≤93% (for intubated patients and for both the phase 2 study and the observational cohort).
- Assisted ventilation from less than 24 hours before registration (only eligible for phase 2).
- Assisted ventilation from more than 24 hours (only eligible for observation cohort).
- Patients already treated with tocilizumab before registration are eligible for the observational cohort only.
- Patient treated with immunomodulators or immunosuppressors.
- Active infections or other clinical conditions that cannot be treated or solved.
- ALT/AST > 5 times the upper limits.
- Neutrophils 3
- Platelets 3
- Diverticulitis or intestinal perforation.
Francesco Perrone, Head of the Clinical Trial Department, National Institute for Oncology Fondazione Pascale, Naples – Principal Investigator of TOCIVID-19
«Our study was designed by the National Health System to support the National Health System. The drug company producing tocilizumab launched on the 19th of March an international randomized trial, also involving 330 patients. We know that randomization is the gold standard for regulatory agencies: but we are experiencing an unprecedented emergency. We cannot randomize the patients, in our view it would be unethical: we have to treat all of them. At the same time, we need to collect reliable data and provide a tool for a proper follow-up of off-label treatments occurring right now all over the country. Our study is the result of a very efficient collaborative effort from many national institutions and it will also help the other countries to face the pandemic. We will use an online platform developed for drug trials in oncology. All our data will be available only for the Italian Medicines Agency. They will decide how to share them to support our doctors and patients».