Efficacy and Safety of MTX-loaded Nanoparticles to Treat Severe COVID-19 Patients

Treatment of Acute Respiratory Syndrome Resulting From the Inflammatory Process of COVID-19 Infection Using Methotrexate-loaded Nanoparticles: A Phase I/II Study

The aim of this study is to evaluate the efficacy and safety of MTX-loaded nanoparticles in three different doses to treat severe COVID-19 patients.

Patients with acute lung injury caused by COVID-19 disease are experiencing an inflammatory reaction that can be harmful and worsen the severity of the clinical condition. Thus, the use of MTX-loaded nanoparticules in patients with acute lung injury secondary to COVID-19 aims to decrease the exacerbated inflammatory reaction leading to a decrease in cell damage caused by this inflammatory process in patients. The study will be divided in 3 phases: Phase A (n=4): IV administration of 20 mg of MTX-loaded nanoparticles. Four doses of Investigational Product (IP) will be administered, once per week. If patients show clinical improvement after 2nd or 3rd administration, the next phase will start. Phase B (n=12): IV administration of 30 mg of MTX-loaded nanoparticles. Four doses of Investigational Product (IP) will be administered, once per week. If patients show clinical improvement after 2nd or 3rd administration, the next phase will start. Fase C (n=26): IV administration of 40 mg of MTX-loaded nanoparticules. Four doses of Investigational Product (IP) will be administered, once per week.

The study will be divided in 3 phases: Phase A: subjects will be dosed 20 mg of MTX IV, once per week (total of 4 doses). Phase B: will only start after 2nd or 3rd administration of phase A. Subjects will be dosed 30 mg of MTX IV, once per week (total of 4 doses). Phase C: will only start after 2nd or 3rd administration of phase B. Subjects will be dosed 40 mg of MTX IV, once per week (total of 4 doses).

Phase B: will only start after 2nd or 3rd administration of phase A. Subjects will be dosed 30 mg of MTX IV, once per week (total of 4 doses).

Phase C: will only start after 2nd or 3rd administration of phase B. Subjects will be dosed 40 mg of MTX IV, once per week (total of 4 doses).

Inclusion Criteria: Informed consent from patient or legal representative. Male or female, aged ≥ 18 years; Acute respiratory distress syndrome; with imminent risk of death, and with chest CT scan with pulmonary impairment greater than 50%; Confirmed or pending diagnosis of COVID-19. Exclusion Criteria: Pleural effusion > 150mL or ascites > 200mL; Chronic liver disease; ALT and AST serum levels >= three times the upper limit of normality; Renal failure (dialysis) Multiple organ failure 7. Concomitant use or use in the last 7 days of cell therapy with stem cells; 8. Any clinical or laboratory condition or comorbidity that, at medical discretion, 9. Known hypersensitivity to the investigational product; 10. Subject who is pregnant or lactating