Clinical trial NCT04352465: Efficacy and Safety of MTX-loaded Nanoparticles to Treat Severe COVID-19 Patients
Official title: Treatment of Acute Respiratory Syndrome Resulting From the Inflammatory Process of COVID-19 Infection Using Methotrexate-loaded Nanoparticles: A Phase I/II Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: COVID-19
Lead sponsor: Azidus Brasil
Sponsor class: INDUSTRY
Collaborators: name: InCor Heart Institute
name: Hospital Santa Marcelina
name: Prevent Senior Institute
First posted: 2020-04-20
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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).
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in clinical conditions
timeFrame: 21 days
Secondary outcomes:
measure: Change of Clinical symptoms - respiratory rate
timeFrame: 21 days
measure: Hypoxia
timeFrame: 21 days
measure: Changes of blood oxygen
timeFrame: 21 days
measure: Inflammatory parameters
timeFrame: 21 days
measure: Evolution of Acute Respiratory Syndrome
timeFrame: 21 days
measure: Hospital discharge
timeFrame: 21 dyas
measure: ICU discharge
timeFrame: 21 days
measure: Rate of mortality
timeFrame: 4 months
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: Prevent Senior Private Operadora de Saúde LTDA.
Study officials:
References: