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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Methotrexate
* Drug: Methotrexate
* Drug: Methotrexate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: 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).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Phase A: subjects will be dosed 20 mg of MTX IV, once per week (total of 4 doses). | Drug: Methotrexate<br>* Phase A: Subjects will be dosed 20 mg of MTX IV, once per week (total of 4 doses).<br>* Other names: MTX-loaded nanoparticles;|
| Experimental: B<br>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). | Drug: Methotrexate<br>* Phase B: Subjects will be dosed 30 mg of MTX IV, once per week (total of 4 doses).<br>* Other names: MTX-loaded nanoparticles;|
| Experimental: C<br>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). | Drug: Methotrexate<br>* Phase C: Subjects will be dosed 40 mg of MTX IV, once per week (total of 4 doses).<br>* Other names: MTX-loaded nanoparticles;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in clinical conditions | Clinical condition will be measured by lung injuries | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Clinical symptoms - respiratory rate | Evaluation of Pneumonia change | 21 days | 
| Hypoxia | oxygen saturation | 21 days | 
| Changes of blood oxygen | PaO2 / FiO2 ratio | 21 days | 
| Inflammatory parameters | C-reactive protein and ferritin | 21 days | 
| Evolution of Acute Respiratory Syndrome | Time to wean off oxygen invasive ventilatory support | 21 days | 
| Hospital discharge | Time to be discharged from hospital | 21 dyas | 
| ICU discharge | Time to be discharged from ICU | 21 days | 
| Rate of mortality | Evaluation of change in acute respiratory syndrome | 4 months |