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

Primary Purpose

Coronavirus Disease 2019 (COVID-19) Pneumonia

Status
Unknown status
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Lenzilumab
Standard of Care
Sponsored by
Humanigen, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Coronavirus Disease 2019 (COVID-19) Pneumonia focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic
  • University of California, Irvine
  • University of Southern California (USC) Medical Center
  • USC - Los Angeles County Medical Center
  • MedStar Washington Hospital Center
  • Mayo Clinic
  • AdventHealth Orlando
  • Emory University
  • St. Elizabeth Healthcare
  • Hennepin County Medical Center
  • Mayo Clinic
  • Dartmouth-Hitchcock
  • Saint Barnabas Medical Center
  • Mercy Medical Center
  • Atrium Health
  • St. David's Healthcare
  • St. David's North Austin Medical Center
  • Texas Health
  • Hospital Vera Cruz
  • CPCLIN - Centro de Pesquisas Clínicas de Natal
  • Hospital São Lucas - PUCRS
  • Sociedade Literaria e Caritativa Santo Agostinho
  • Hospital Dia do Pulmão
  • Hospital Guilherme Alvaro
  • Clinica de Alergia Martti Antila S/S LTDA
  • CEMEC - Centro Multidisciplinar de Estudos Clínicos LTDA-EPP
  • Escola Paulista de Medicina (UNIFESP)
  • Hospital Heliópolis
  • Hospital São Luiz do Jabaquara/IDOR

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Lenzilumab Arm

Placebo Arm

Arm Description

Participants will receive IV infusion of lenzilumab upon randomization at a pre-specified dosing interval and continued administration of 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

Outcomes

Primary Outcome Measures

Ventilator-free Survival

Secondary Outcome Measures

Ventilator-free Days
Duration of Intensive Care Unit (ICU) Stay
Incidence of Invasive Mechanical Ventilation, ECMO and/or Death
Time to Death
All-cause Mortality
Time to Recovery
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)
Duration of Hospitalization
Time to Improvement in 1 or 2 Categories using 8-point Ordinal Scale
Number of Subjects Alive and Off Oxygen
Percentage of Participants Experiencing Adverse Events
Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Percentage of Participants Experiencing Serious Adverse Events
Using the NCI CTCAE version 5.0
Proportion of Subjects Discharged from Hospital
Time to improvement in oxygenation for > 48 hours
Incidence of Non-invasive Ventilation (or Use of High-flow Oxygen Device)
Time to Clinical Improvement, Defined as NEWS2 < 2 Maintained for 24 Hours
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
Duration of Time on Low-flow or High-flow Supplemental Oxygen

Full Information

First Posted
April 15, 2020
Last Updated
March 1, 2021
Sponsor
Humanigen, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04351152
Brief Title
Phase 3 Study to Evaluate Efficacy and Safety of Lenzilumab in Patients With COVID-19
Official Title
A Phase 3 Randomized, Placebo-Controlled Study of Lenzilumab in Hospitalized Patients With Severe and Critical COVID-19 Pneumonia
Study Type
Interventional

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Unknown status
Study Start Date
May 5, 2020 (Actual)
Primary Completion Date
March 2021 (Anticipated)
Study Completion Date
March 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Humanigen, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronavirus Disease 2019 (COVID-19) Pneumonia
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Masking Description
Double-Blind
Allocation
Randomized
Enrollment
520 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lenzilumab Arm
Arm Type
Experimental
Arm Description
Participants will receive IV infusion of lenzilumab upon randomization at a pre-specified dosing interval and continued administration of standard of care
Arm Title
Placebo Arm
Arm Type
Placebo Comparator
Arm Description
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 Type
Biological
Intervention Name(s)
Lenzilumab
Other Intervention Name(s)
Humaneered® anti-human GM-CSF monoclonal Antibody
Intervention Description
Administered as an intravenous (IV) infusion
Intervention Type
Drug
Intervention Name(s)
Standard of Care
Intervention Description
Standard of care therapy can include remdesivir and/or dexamethasone per institutional treatment guidelines or written policies
Primary Outcome Measure Information:
Title
Ventilator-free Survival
Time Frame
Up to Day 28
Secondary Outcome Measure Information:
Title
Ventilator-free Days
Time Frame
Up to Day 28
Title
Duration of Intensive Care Unit (ICU) Stay
Time Frame
Up to Day 28
Title
Incidence of Invasive Mechanical Ventilation, ECMO and/or Death
Time Frame
Up to Day 28
Title
Time to Death
Time Frame
Up to Day 28
Title
All-cause Mortality
Time Frame
Day 28
Title
Time to Recovery
Description
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).
Time Frame
Up to Day 28
Title
Incidence of severe acute respiratory distress syndrome (ARDS)
Time Frame
Up to Day 28
Title
Duration of Hospitalization
Time Frame
Up to Day 28
Title
Time to Improvement in 1 or 2 Categories using 8-point Ordinal Scale
Time Frame
Up to Day 28
Title
Number of Subjects Alive and Off Oxygen
Time Frame
Up to Day 60
Title
Percentage of Participants Experiencing Adverse Events
Description
Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Time Frame
Up to Day 60
Title
Percentage of Participants Experiencing Serious Adverse Events
Description
Using the NCI CTCAE version 5.0
Time Frame
Up to Day 60
Title
Proportion of Subjects Discharged from Hospital
Time Frame
Up to Day 60
Title
Time to improvement in oxygenation for > 48 hours
Time Frame
Up to Day 28
Title
Incidence of Non-invasive Ventilation (or Use of High-flow Oxygen Device)
Time Frame
Up to Day 28
Title
Time to Clinical Improvement, Defined as NEWS2 < 2 Maintained for 24 Hours
Description
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)
Time Frame
Up to Day 28
Title
Change from Baseline to Day 28 in Clinical status Based on the 8-point Ordinal Scale
Time Frame
Up to Day 28
Title
Duration of Time on Low-flow or High-flow Supplemental Oxygen
Time Frame
Up to Day 28

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cameron Durrant, MD
Organizational Affiliation
Humanigen, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Mayo Clinic
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Facility Name
University of California, Irvine
City
Irvine
State/Province
California
ZIP/Postal Code
92697
Country
United States
Facility Name
University of Southern California (USC) Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
USC - Los Angeles County Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
MedStar Washington Hospital Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Mayo Clinic
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32216
Country
United States
Facility Name
AdventHealth Orlando
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
St. Elizabeth Healthcare
City
Edgewood
State/Province
Kentucky
ZIP/Postal Code
41017
Country
United States
Facility Name
Hennepin County Medical Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55415
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Dartmouth-Hitchcock
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
Saint Barnabas Medical Center
City
Livingston
State/Province
New Jersey
ZIP/Postal Code
07039
Country
United States
Facility Name
Mercy Medical Center
City
Rockville Centre
State/Province
New York
ZIP/Postal Code
11570
Country
United States
Facility Name
Atrium Health
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203
Country
United States
Facility Name
St. David's Healthcare
City
Austin
State/Province
Texas
ZIP/Postal Code
78705
Country
United States
Facility Name
St. David's North Austin Medical Center
City
Austin
State/Province
Texas
ZIP/Postal Code
78758
Country
United States
Facility Name
Texas Health
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
Hospital Vera Cruz
City
Belo Horizonte
State/Province
Minas Gerais
ZIP/Postal Code
30140-060
Country
Brazil
Facility Name
CPCLIN - Centro de Pesquisas Clínicas de Natal
City
Natal
State/Province
Rio Grande Do Norte
ZIP/Postal Code
59025-050
Country
Brazil
Facility Name
Hospital São Lucas - PUCRS
City
Porto Alegre
State/Province
Rio Grande Do Sul
ZIP/Postal Code
90610-000
Country
Brazil
Facility Name
Sociedade Literaria e Caritativa Santo Agostinho
City
Criciúma
State/Province
Santa Catarina
ZIP/Postal Code
88811-500
Country
Brazil
Facility Name
Hospital Dia do Pulmão
City
Blumenau
State/Province
São Paulo
ZIP/Postal Code
89030-101
Country
Brazil
Facility Name
Hospital Guilherme Alvaro
City
Santos
State/Province
São Paulo
ZIP/Postal Code
11045-904
Country
Brazil
Facility Name
Clinica de Alergia Martti Antila S/S LTDA
City
Sorocaba
State/Province
São Paulo
ZIP/Postal Code
18040-425
Country
Brazil
Facility Name
CEMEC - Centro Multidisciplinar de Estudos Clínicos LTDA-EPP
City
São Bernardo do Campo
State/Province
São Paulo
ZIP/Postal Code
09715-090
Country
Brazil
Facility Name
Escola Paulista de Medicina (UNIFESP)
City
São Paulo
ZIP/Postal Code
04037-002
Country
Brazil
Facility Name
Hospital Heliópolis
City
São Paulo
ZIP/Postal Code
04231-030
Country
Brazil
Facility Name
Hospital São Luiz do Jabaquara/IDOR
City
São Paulo
ZIP/Postal Code
04501-000
Country
Brazil

12. IPD Sharing Statement

Plan to Share IPD
Yes
Citations:
PubMed Identifier
35793833
Citation
Temesgen Z, Kelley CF, Cerasoli F, Kilcoyne A, Chappell D, Durrant C, Ahmed O, Chappell G, Catterson V, Polk C, Badley A, Marconi VC; LIVE-AIR Study Group. C reactive protein utilisation, a biomarker for early COVID-19 treatment, improves lenzilumab efficacy: results from the randomised phase 3 'LIVE-AIR' trial. Thorax. 2023 Jun;78(6):606-616. doi: 10.1136/thoraxjnl-2022-218744. Epub 2022 Jul 6.
Results Reference
derived
PubMed Identifier
34863332
Citation
Temesgen Z, Burger CD, Baker J, Polk C, Libertin CR, Kelley CF, Marconi VC, Orenstein R, Catterson VM, Aronstein WS, Durrant C, Chappell D, Ahmed O, Chappell G, Badley AD; LIVE-AIR Study Group. Lenzilumab in hospitalised patients with COVID-19 pneumonia (LIVE-AIR): a phase 3, randomised, placebo-controlled trial. Lancet Respir Med. 2022 Mar;10(3):237-246. doi: 10.1016/S2213-2600(21)00494-X. Epub 2021 Dec 1.
Results Reference
derived
PubMed Identifier
33972949
Citation
Temesgen Z, Burger CD, Baker J, Polk C, Libertin C, Kelley C, Marconi VC, Orenstein R, Durrant C, Chappell D, Ahmed O, Chappell G, Badley AD. LENZILUMAB EFFICACY AND SAFETY IN NEWLY HOSPITALIZED COVID-19 SUBJECTS: RESULTS FROM THE LIVE-AIR PHASE 3 RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROLLED TRIAL. medRxiv. 2021 May 5:2021.05.01.21256470. doi: 10.1101/2021.05.01.21256470. Preprint.
Results Reference
derived
PubMed Identifier
33673929
Citation
Aroldi A, Chiarle R, Gambacorti-Passerini C. Clinical Benefit of Lenzilumab in Cases of Coronavirus Disease 2019. Mayo Clin Proc. 2021 Mar;96(3):817. doi: 10.1016/j.mayocp.2020.12.030. Epub 2021 Jan 11. No abstract available.
Results Reference
derived
PubMed Identifier
33153629
Citation
Temesgen Z, Assi M, Shweta FNU, Vergidis P, Rizza SA, Bauer PR, Pickering BW, Razonable RR, Libertin CR, Burger CD, Orenstein R, Vargas HE, Palraj R, Dababneh AS, Chappell G, Chappell D, Ahmed O, Sakemura R, Durrant C, Kenderian SS, Badley AD. GM-CSF Neutralization With Lenzilumab in Severe COVID-19 Pneumonia: A Case-Cohort Study. Mayo Clin Proc. 2020 Nov;95(11):2382-2394. doi: 10.1016/j.mayocp.2020.08.038. Epub 2020 Sep 3.
Results Reference
derived

Learn more about this trial

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

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