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.
Biological: Lenzilumab
Administered as an intravenous (IV) infusion
Other Name: Humaneered® anti-human GM-CSF monoclonal Antibody
Drug: Standard of Care
Standard of care therapy can include remdesivir and/or dexamethasone per institutional treatment guidelines or written policies
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
Mayo Clinic
Phoenix, Arizona, United States
University of California, Irvine
Irvine, California, United States
University of Southern California (USC) Medical Center
Los Angeles, California, United States
USC - Los Angeles County Medical Center
Los Angeles, California, United States
MedStar Washington Hospital Center
Washington, District of Columbia, United States
Mayo Clinic
Jacksonville, Florida, United States
AdventHealth Orlando
Orlando, Florida, United States
Emory University
Atlanta, Georgia, United States
St. Elizabeth Healthcare
Edgewood, Kentucky, United States
Hennepin County Medical Center
Minneapolis, Minnesota, United States
Mayo Clinic
Rochester, Minnesota, United States
Dartmouth-Hitchcock
Lebanon, New Hampshire, United States
Saint Barnabas Medical Center
Livingston, New Jersey, United States
Mercy Medical Center
Rockville Centre, New York, United States
Atrium Health
Charlotte, North Carolina, United States
St. David's Healthcare
Austin, Texas, United States
St. David's North Austin Medical Center
Austin, Texas, United States
Texas Health
Dallas, Texas, United States
Hospital Vera Cruz
Belo Horizonte, Minas Gerais, Brazil
CPCLIN - Centro de Pesquisas Clínicas de Natal
Natal, Rio Grande Do Norte, Brazil
Hospital São Lucas - PUCRS
Porto Alegre, Rio Grande Do Sul, Brazil
Sociedade Literaria e Caritativa Santo Agostinho
Criciúma, Santa Catarina, Brazil
Hospital Dia do Pulmão
Blumenau, São Paulo, Brazil
Hospital Guilherme Alvaro
Santos, São Paulo, Brazil
Clinica de Alergia Martti Antila S/S LTDA
Sorocaba, São Paulo, Brazil
CEMEC - Centro Multidisciplinar de Estudos Clínicos LTDA-EPP
São Bernardo do Campo, São Paulo, Brazil
Escola Paulista de Medicina (UNIFESP)
São Paulo, Brazil
Hospital Heliópolis
São Paulo, Brazil
Hospital São Luiz do Jabaquara/IDOR
São Paulo, Brazil
Cameron Durrant, MD, Study Director
Humanigen, Inc.