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

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ClinicalTrials.gov Identifier: NCT04351152
Recruitment Status : Active, not recruiting
First Posted : April 17, 2020
Last Update Posted : March 3, 2021
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Coronavirus Disease 2019 (COVID-19) Pneumonia Biological: Lenzilumab Drug: Standard of Care Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 520 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description: Double-Blind
Primary Purpose: Treatment
Official Title: A Phase 3 Randomized, Placebo-Controlled Study of Lenzilumab in Hospitalized Patients With Severe and Critical COVID-19 Pneumonia
Actual Study Start Date : May 5, 2020
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : March 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pneumonia

Arm Intervention/treatment
Experimental: Lenzilumab Arm
Participants will receive IV infusion of lenzilumab upon randomization at a pre-specified dosing interval and continued administration of standard of care
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

Placebo Comparator: 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
Drug: Standard of Care
Standard of care therapy can include remdesivir and/or dexamethasone per institutional treatment guidelines or written policies




Primary Outcome Measures :
  1. Ventilator-free Survival [ Time Frame: Up to Day 28 ]

Secondary Outcome Measures :
  1. Ventilator-free Days [ Time Frame: Up to Day 28 ]
  2. Duration of Intensive Care Unit (ICU) Stay [ Time Frame: Up to Day 28 ]
  3. Incidence of Invasive Mechanical Ventilation, ECMO and/or Death [ Time Frame: Up to Day 28 ]
  4. Time to Death [ Time Frame: Up to Day 28 ]
  5. All-cause Mortality [ Time Frame: Day 28 ]
  6. Time to Recovery [ Time Frame: 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).

  7. Incidence of severe acute respiratory distress syndrome (ARDS) [ Time Frame: Up to Day 28 ]
  8. Duration of Hospitalization [ Time Frame: Up to Day 28 ]
  9. Time to Improvement in 1 or 2 Categories using 8-point Ordinal Scale [ Time Frame: Up to Day 28 ]
  10. Number of Subjects Alive and Off Oxygen [ Time Frame: Up to Day 60 ]
  11. Percentage of Participants Experiencing Adverse Events [ Time Frame: Up to Day 60 ]
    Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

  12. Percentage of Participants Experiencing Serious Adverse Events [ Time Frame: Up to Day 60 ]
    Using the NCI CTCAE version 5.0

  13. Proportion of Subjects Discharged from Hospital [ Time Frame: Up to Day 60 ]
  14. Time to improvement in oxygenation for > 48 hours [ Time Frame: Up to Day 28 ]
  15. Incidence of Non-invasive Ventilation (or Use of High-flow Oxygen Device) [ Time Frame: Up to Day 28 ]
  16. Time to Clinical Improvement, Defined as NEWS2 < 2 Maintained for 24 Hours [ Time Frame: 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)

  17. Change from Baseline to Day 28 in Clinical status Based on the 8-point Ordinal Scale [ Time Frame: Up to Day 28 ]
  18. Duration of Time on Low-flow or High-flow Supplemental Oxygen [ Time Frame: Up to Day 28 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04351152


Locations
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Sponsors and Collaborators
Humanigen, Inc.
Investigators
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Study Director: Cameron Durrant, MD Humanigen, Inc.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Humanigen, Inc.
ClinicalTrials.gov Identifier: NCT04351152    
Other Study ID Numbers: HGEN003-06
First Posted: April 17, 2020    Key Record Dates
Last Update Posted: March 3, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Humanigen, Inc.:
Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF)
GM-CSF monoclonal antibody
Cytokine Release Syndrome (CRS)
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
Lenzilumab
Cytokine Storm
Additional relevant MeSH terms:
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Coronavirus Infections
Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs