A Phase 3 Randomized, Placebo-Controlled Study of Lenzilumab in Hospitalized Patients With Severe and Critical COVID-19 Pneumonia
Overview
- Phase
- Phase 3
- Intervention
- Lenzilumab
- Conditions
- Coronavirus Disease 2019 (COVID-19) Pneumonia
- Sponsor
- Humanigen, Inc.
- Enrollment
- 520
- Locations
- 27
- Primary Endpoint
- Ventilator-free Survival
- Last Updated
- 5 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
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
Arms & Interventions
Lenzilumab Arm
Participants will receive IV infusion of lenzilumab upon randomization at a pre-specified dosing interval and continued administration of standard of care
Intervention: Lenzilumab
Lenzilumab Arm
Participants will receive IV infusion of lenzilumab upon randomization at a pre-specified dosing interval and continued administration of standard of care
Intervention: Standard of Care
Placebo Arm
Participants will receive IV infusion of preservative-free 0.9% sodium chloride solution upon randomization matched to lenzilumab at same pre-specified dosing interval and continued administration of standard of care
Intervention: Standard of Care
Outcomes
Primary Outcomes
Ventilator-free Survival
Time Frame: Up to Day 28
Secondary Outcomes
- Ventilator-free Days(Up to Day 28)
- Duration of Intensive Care Unit (ICU) Stay(Up to Day 28)
- Percentage of Participants Experiencing Serious Adverse Events(Up to Day 60)
- Incidence of Invasive Mechanical Ventilation, ECMO and/or Death(Up to Day 28)
- Time to Death(Up to Day 28)
- All-cause Mortality(Day 28)
- Time to Recovery(Up to Day 28)
- Incidence of severe acute respiratory distress syndrome (ARDS)(Up to Day 28)
- Proportion of Subjects Discharged from Hospital(Up to Day 60)
- Duration of Hospitalization(Up to Day 28)
- Time to Improvement in 1 or 2 Categories using 8-point Ordinal Scale(Up to Day 28)
- Number of Subjects Alive and Off Oxygen(Up to Day 60)
- Percentage of Participants Experiencing Adverse Events(Up to Day 60)
- Time to improvement in oxygenation for > 48 hours(Up to Day 28)
- Incidence of Non-invasive Ventilation (or Use of High-flow Oxygen Device)(Up to Day 28)
- Time to Clinical Improvement, Defined as NEWS2 < 2 Maintained for 24 Hours(Up to Day 28)
- Change from Baseline to Day 28 in Clinical status Based on the 8-point Ordinal Scale(Up to Day 28)
- Duration of Time on Low-flow or High-flow Supplemental Oxygen(Up to Day 28)