A Randomized Phase 2b Trial Evaluating Clinical Outcomes of Inhaled Sargramostim in High-risk Patients With Mild-moderate COVID-19
Overview
- Phase
- Phase 2
- Intervention
- Sargramostim
- Conditions
- Covid19
- Sponsor
- Partner Therapeutics, Inc.
- Enrollment
- 600
- Locations
- 36
- Primary Endpoint
- Number of Participants With an Emergency Room Visit or Hospitalization, or Death by Day 28
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
- •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
Exclusion Criteria
- •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
Arms & Interventions
Sargramostim Arm
Day 1 - 5: Sargramostim treatment in addition to standard of care for COVID-19
Intervention: Sargramostim
Placebo Arm
Day 1 - 5: Placebo treatment in addition to standard of care for COVID-19
Intervention: Placebo
Outcomes
Primary Outcomes
Number of Participants With an Emergency Room Visit or Hospitalization, or Death by Day 28
Time Frame: 28 days
Percentage of patients who experience any emergency room visit or hospitalization, or death
Secondary Outcomes
- Disease Progression Based on NIAID Score(Day 28 and Day 60)
- Time to Disease Progression Based on NIAID Score(Day 28 and Day 60)
- Number of Participants With Adverse Events(60 days)
- Change From Baseline in Overall Symptom Scores(Day 7, 14, and 28)