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.

Study Overview

• Status: Unknown
• Conditions: COVID-19
• Intervention / Treatment: Drug: Methotrexate; Drug: Methotrexate; Drug: Methotrexate

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 Type: Interventional
• Enrollment (Anticipated): 42
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil
    • Prevent Senior Private Operadora de Saúde LTDA.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Azidus Brasil
• Collaborators: InCor Heart Institute; Hospital Santa Marcelina; Prevent Senior Institute

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): May 1, 2020
• Primary Completion (ANTICIPATED): June 30, 2020
• Study Completion (ANTICIPATED): November 30, 2020

Study Registration Dates

• First Submitted: April 15, 2020
• First Submitted That Met QC Criteria: April 15, 2020
• First Posted (ACTUAL): April 20, 2020

Study Record Updates

• Last Update Posted (ACTUAL): April 29, 2020
• Last Update Submitted That Met QC Criteria: April 27, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate
• Other Study ID Numbers: LDE-MTX_COVID19

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No