Phase 3 Study to Evaluate Efficacy and Safety of Lenzilumab in Patients With COVID-19
- Conditions
- Coronavirus Disease 2019 (COVID-19) Pneumonia
- Interventions
- Biological: LenzilumabDrug: Standard of Care
- Registration Number
- NCT04351152
- Lead Sponsor
- Humanigen, Inc.
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 520
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lenzilumab Arm Standard of Care Participants will receive IV infusion of lenzilumab upon randomization at a pre-specified dosing interval and continued administration of standard of care Placebo Arm Standard of Care 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 Lenzilumab Arm Lenzilumab Participants will receive IV infusion of lenzilumab upon randomization at a pre-specified dosing interval and continued administration of standard of care
- Primary Outcome Measures
Name Time Method Ventilator-free Survival Up to Day 28
- Secondary Outcome Measures
Name Time Method Time to Death Up to Day 28 Ventilator-free Days Up to Day 28 Duration of Intensive Care Unit (ICU) Stay Up to Day 28 Incidence of Invasive Mechanical Ventilation, ECMO and/or Death Up to Day 28 All-cause Mortality Day 28 Time to Recovery Up to Day 28 Time to recovery is defined as the first day on which a subject satisfies one of the following 3 categories from the 8-point ordinal scale (Hospitalized, not requiring supplemental oxygen-no longer requires ongoing medical care; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities).
Incidence of severe acute respiratory distress syndrome (ARDS) Up to Day 28 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 Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Percentage of Participants Experiencing Serious Adverse Events Up to Day 60 Using the NCI CTCAE version 5.0
Proportion of Subjects Discharged from Hospital 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 NEWS2 consists of: Physiological Parameters: respiration rate (per minute), SpO2 Scale 1 (%), SpO2 Scale 2 (%), use of air or oxygen, systolic blood pressure (mmHg), pulse (per minute), consciousness and temperature (°C)
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
Trial Locations
- Locations (27)
MedStar Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
Dartmouth-Hitchcock
🇺🇸Lebanon, New Hampshire, United States
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
Atrium Health
🇺🇸Charlotte, North Carolina, United States
Hospital Heliópolis
🇧🇷São Paulo, Brazil
Hospital São Lucas - PUCRS
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Escola Paulista de Medicina (UNIFESP)
🇧🇷São Paulo, Brazil
CPCLIN - Centro de Pesquisas Clínicas de Natal
🇧🇷Natal, Rio Grande Do Norte, Brazil
Hospital Vera Cruz
🇧🇷Belo Horizonte, Minas Gerais, Brazil
Hospital Dia do Pulmão
🇧🇷Blumenau, São Paulo, Brazil
Sociedade Literaria e Caritativa Santo Agostinho
🇧🇷Criciúma, Santa Catarina, Brazil
Hospital São Luiz do Jabaquara/IDOR
🇧🇷São Paulo, Brazil
St. Elizabeth Healthcare
🇺🇸Edgewood, Kentucky, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
AdventHealth Orlando
🇺🇸Orlando, Florida, United States
Hennepin County Medical Center
🇺🇸Minneapolis, Minnesota, United States
Saint Barnabas Medical Center
🇺🇸Livingston, New Jersey, United States
St. David's North Austin Medical Center
🇺🇸Austin, Texas, United States
University of California, Irvine
🇺🇸Irvine, California, United States
Mercy Medical Center
🇺🇸Rockville Centre, New York, 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
Emory University
🇺🇸Atlanta, Georgia, United States
St. David's Healthcare
🇺🇸Austin, Texas, United States
Texas Health
🇺🇸Dallas, Texas, United States