Resumen

The purpose of this research is to understand if the study drug, also called sargramostim or Leukine®, can help prevent the worsening of COVID-19 when the study drug is inhaled. This study will also help researchers understand if inhaled sargramostim can help prevent visits to the emergency room or hospitalization, or death.

Descripción detallada

This Phase 2b, multicenter, placebo-controlled, double-blind study will randomize approximately 500 adult patients who are symptomatic with mild or moderate COVID-19 (as defined in the FDA Guidance Document: Covid-19: Developing Drugs and Biological Products for Treatment or Prevention, May 2020) who are at high risk for progression to more severe disease. Patients will be randomized in a 1:1 ratio to inhaled sargramostim plus standard of care (SOC) or placebo plus SOC. Enrollment of patients who have completed a COVID-19 vaccination regimen or participated in a COVID-19 vaccine clinical trial will be capped at approximately 100 patients. All patients will be randomized to receive either 250 mcg of sargramostim or equivalent volume of placebo diluent. Treatment will be administered once daily for 5 days delivered via a vibrating mesh nebulizer. Patients will be followed for up to 60 days after start of treatment. Sargramostim (Leukine) is a formulation of Granulocyte Macrophage Colony Stimulating Factor (GM-CSF), which is a critical cytokine for healthy pulmonary function. Detailed studies have shown that GM-CSF is necessary for alveolar macrophage (AM) maturation and maintenance. Although GM-CSF was discovered as a myelopoietic growth factor, it has diverse additional effects that both promote differentiation of myeloid precursors into neutrophils, monocytes, and dendritic cells and control function of mature myeloid cells. GM-CSF is also known to reverse immunoparalysis seen in sepsis, resulting in beneficial outcomes. In addition, GM-CSF prevents bacteremia in post influenza bacterial pneumonia through locally mediated improved lung antibacterial resistance and increased reactive oxygen species production by AMs. Pulmonary delivery of this GM-CSF has potential to reduce morbidity and mortality due to viral pneumonias, potentially including COVID-19.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Patients with a positive laboratory diagnosis of SARS-CoV-2 infection by an antigen or a molecular test ≤5 days prior to randomization. The test should have been authorized by the relevant regulatory authority.
Have one or more of the following mild or moderate COVID-19 symptoms for ≤5 days prior to randomization:
Fever or chills
New onset or worsening cough
Sore throat
Malaise or fatigue
Headache
Muscle pain (myalgias) or body aches
Gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea)
New onset or worsening shortness of breath or difficulty breathing
Nasal congestion or runny nose
New loss of taste (ageusia) and/or smell (anosmia). Note: any of these symptoms (ageusia, anosmia) alone or in combination cannot be used as the SOLE qualifying symptoms for enrollment.
At higher risk for progression to more severe COVID-19
Age ≥ 60 years
Age 18-59 years with a clinically stable medical history of at least 1 or more of the following conditions that could lead to severe COVID-19:
Chronic respiratory conditions such as asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis
Obesity with BMI ≥ 30 kg/m2
Cardiovascular disease
Sickle cell disease or thalassemia
Diabetes mellitus being managed with concomitant medications
Hypertension being managed with concomitant medications
Chronic kidney disease
Oxygen saturation by pulse oximeter \> 93% on room air. Note: at altitudes of \>4000 feet above sea level, oxygen saturation by pulse oximeter \> 91% on room air is permitted
Negative pregnancy test (if woman of childbearing potential)
Females of childbearing potential and males with female partners of childbearing potential must agree to use acceptable contraceptive methods from screening to Day 28
The patient (or legally authorized decision maker) must give informed consent

Criterios de exclusión

Hospitalized patients
Patients who have received or are receiving other treatments that are not approved/authorized by the relevant regulatory authority for the treatment of patients with mild or moderate COVID-19 in an outpatient setting
Patients enrolled in interventional clinical trials for other experimental therapies
Patients on chronic oxygen supplementation due to cardiopulmonary or other conditions
Patients with unstable comorbid conditions (e.g., decompensated congestive heart failure, COPD with exacerbation, current angina pectoris, uncontrolled diabetes mellitus, uncontrolled hypertension, uncontrolled asthma)
Patients with severe pulmonary comorbid conditions, including systemic steroid-dependent asthma, systemic steroid-dependent COPD, oxygen-dependent COPD, lung transplant, or cystic fibrosis
Patients who have received highly immunosuppressive therapy (to include systemic corticosteroids) or anti-cancer combination chemotherapy within 24 hours prior to first dose of study drug
Patients with known or suspected intolerance or hypersensitivity to sargramostim, or any component of the product
Patients who have previously experienced severe and unexplained side effects during aerosol delivery of any kind of medical product
Pregnant or breastfeeding females
Patients who, in the opinion of the Investigator, will not be able to comply with all the study procedures and visits as outlined in the schedule of events, including follow-up

Intervenciones

drug

Sargramostim

All patients randomized to the sargramostim treatment arm will be treated with 250 mcg inhaled sargramostim administered via a vibrating mesh nebulizer once daily for 5 days.

drug

Placebo

All patients in the control arm will receive an equivalent volume of inhaled placebo diluent administered via a vibrating mesh nebulizer once daily for 5 days.

A Randomized Phase 2b Trial Evaluating Clinical Outcomes of Inhaled Sargramostim in High-risk Patients With Mild-moderate COVID-19

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Sargramostim

Placebo

Ubicaciones

Centro de Investigaciones Medicas Mar del Plata

Instituto Medico de la Fundacion Estudios Clinicos

Sanatorio Santa Barbara

Patrocinadores