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.

Inclusion Criteria:

1. Informed consent from patient or legal representative.
2. Male or female, aged ≥ 18 years;
3. Acute respiratory distress syndrome; with imminent risk of death, and with chest CT scan with pulmonary impairment greater than 50%;
4. Confirmed or pending diagnosis of COVID-19.

Exclusion Criteria:

1. Pleural effusion > 150mL or ascites > 200mL;
2. Chronic liver disease;
3. ALT and AST serum levels >= three times the upper limit of normality;
4. Renal failure (dialysis)
5. 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