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

Azidus

Status and phase: Unknown; Phase 2; Phase 1

Conditions: COVID-19

Treatments: Drug: Methotrexate

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04352465

LDE-MTX_COVID19

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 42 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

6. 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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42 participants in 3 patient groups

A

Experimental group

Description:

Phase A: subjects will be dosed 20 mg of MTX IV, once per week (total of 4 doses).

Treatment:

Drug: Methotrexate

Drug: Methotrexate

Drug: Methotrexate

B

Experimental group

Description:

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).

Treatment:

Drug: Methotrexate

Drug: Methotrexate

Drug: Methotrexate

C

Experimental group

Description:

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).

Treatment:

Drug: Methotrexate

Drug: Methotrexate

Drug: Methotrexate