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

Phase 1

• Conditions: COVID-19
• Interventions: Drug: Methotrexate

• Registration Number: NCT04352465
• Lead Sponsor: Azidus Brasil

Brief Summary

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

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.

Study Timeline

• Status Verified: 2020-04
• Study First Submitted: 2020-04-15
• Study First Submitted QC: 2020-04-15
• Study First Posted: 2020-04-20
• Last Update Submitted: 2020-04-27
• Last Update Posted: 2020-04-29
• Study Start: 2020-05-01
• Primary Completion: 2020-06-30
• Study Completion: 2020-11-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 42

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
B	Methotrexate	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).
A	Methotrexate	Phase A: subjects will be dosed 20 mg of MTX IV, once per week (total of 4 doses).
C	Methotrexate	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).

Primary Outcome Measures

Name	Time	Method
Change in clinical conditions	21 days	Clinical condition will be measured by lung injuries

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Prevent Senior Private Operadora de Saúde LTDA.; 🇧🇷 São Paulo, Brazil