Phase 3 Study to Evaluate Efficacy and Safety of Lenzilumab in Patients With COVID-19

The primary objective of this study is to assess whether the use of lenzilumab in addition to current standard of care can alleviate the immune-mediated cytokine release syndrome (CRS) and improve ventilator-free survival in hospitalized subjects with severe or critical COVID-19 pneumonia.

In COVID-19, high levels of granulocyte macrophage-colony stimulating factor (GM-CSF) and inflammatory myeloid cells correlate with disease severity, cytokine storm, and respiratory failure. The mortality rate for hospitalized COVID-19 patients remains unacceptably high, particularly in patients who progress to invasive mechanical ventilation (IMV). This randomized, double-blind, multicenter, placebo-controlled pivotal phase 3 trial will evaluate the impact of lenzilumab (anti-human GM-CSF monoclonal antibody) on ventilator-free survival in hospitalized, hypoxic patients with COVID-19. The study is also designed to evaluate other key endpoints, including ventilator-free days, duration of ICU stay, incidence of IMV, ECMO and/or death, time to death, all-cause mortality and time to recovery.

Approximately 516 patients will be randomized to receive lenzilumab + SOC vs. placebo + SOC in a 1:1 ratio.

Eligibility Criteria:
Inclusion Criteria:

* Adults 18 years of age or older who are capable of providing informed consent or have a proxy capable of giving consent for them
* Virologic confirmation of SARS-CoV-2 infection via any FDA authorized diagnostic test for SARS-CoV-2
* Pneumonia diagnosed by Chest X-ray or Computed Tomography revealing infiltrates consistent with pneumonia
* SpO2 ≤ 94% on room air and/or require low-flow supplemental oxygen and/or require high-flow oxygen support or NIPPV
* Hospitalized, not requiring invasive mechanical ventilation during this hospitalization
* Have not participated in other clinical trial for COVID-19 using an immunomodulatory monoclonal antibody or kinase inhibitor (use of remdesivir, corticosteroids, convalescent plasma, hydroxychloroquine or chloroquine is permitted)
* Females of childbearing potential must have a negative serum or urine pregnancy test

Exclusion Criteria:

* Requiring invasive mechanical ventilation or extracorporeal membrane oxygenation prior to randomization
* Confirmed diagnosis of bacterial pneumonia or other active/uncontrolled fungal or viral infections at screening/baseline
* Known active tuberculosis (TB), history of incompletely treated TB or suspected or known extrapulmonary TB
* Currently receiving treatment for hepatitis A, hepatitis B, hepatitis C or HIV infection
* History of pulmonary alveolar proteinosis (PAP)
* Women of childbearing potential who are pregnant or breastfeeding
* Known hypersensitivity to lenzilumab or any of its components
* Use of any FDA authorized anti-IL-6 (e.g., tocilizumab, sarilumab, sitlukimab), anti-IL-1 (e.g., anakinra, canakinumab), kinase inhibitor (e.g., baracitinib, ibrutinib, acalabrutinib), or neutralizing monoclonal antibody (e.g. bamlanivimab or casirivimab/imdevimab) therapy to treat COVID-19 within 8 weeks prior to randomization
* Use of GM-CSF agents (e.g., sargramostim) within prior 2 months of randomization
* Expected survival \< 48h in the opinion of the investigator
* Any condition that, in the opinion of the investigator, is likely to interfere with the safety and efficacy of the study treatment or puts the patient at unacceptably high risk from the study