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

March 1, 2021 updated by: Humanigen, Inc.

A Phase 3 Randomized, Placebo-Controlled Study of Lenzilumab in Hospitalized Patients With Severe and Critical COVID-19 Pneumonia

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

520

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
      • São Paulo, Brazil, 04037-002
        • Escola Paulista de Medicina (UNIFESP)
      • São Paulo, Brazil, 04231-030
        • Hospital Heliópolis
      • São Paulo, Brazil, 04501-000
        • Hospital São Luiz do Jabaquara/IDOR
    • Minas Gerais
      • Belo Horizonte, Minas Gerais, Brazil, 30140-060
        • Hospital Vera Cruz
    • Rio Grande Do Norte
      • Natal, Rio Grande Do Norte, Brazil, 59025-050
        • CPCLIN - Centro de Pesquisas Clínicas de Natal
    • Rio Grande Do Sul
      • Porto Alegre, Rio Grande Do Sul, Brazil, 90610-000
        • Hospital Sao Lucas - PUCRS
    • Santa Catarina
      • Criciúma, Santa Catarina, Brazil, 88811-500
        • Sociedade Literaria e Caritativa Santo Agostinho
    • São Paulo
      • Blumenau, São Paulo, Brazil, 89030-101
        • Hospital Dia do Pulmao
      • Santos, São Paulo, Brazil, 11045-904
        • Hospital Guilherme Alvaro
      • Sorocaba, São Paulo, Brazil, 18040-425
        • Clinica de Alergia Martti Antila S/S Ltda
      • São Bernardo do Campo, São Paulo, Brazil, 09715-090
        • CEMEC - Centro Multidisciplinar de Estudos Clínicos LTDA-EPP
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic
    • California
      • Irvine, California, United States, 92697
        • University of California, Irvine
      • Los Angeles, California, United States, 90033
        • University of Southern California (USC) Medical Center
      • Los Angeles, California, United States, 90033
        • USC - Los Angeles County Medical Center
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • MedStar Washington Hospital Center
    • Florida
      • Jacksonville, Florida, United States, 32216
        • Mayo Clinic
      • Orlando, Florida, United States, 32803
        • AdventHealth Orlando
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University
    • Kentucky
      • Edgewood, Kentucky, United States, 41017
        • St. Elizabeth Healthcare
    • Minnesota
      • Minneapolis, Minnesota, United States, 55415
        • Hennepin County Medical Center
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth-Hitchcock
    • New Jersey
      • Livingston, New Jersey, United States, 07039
        • Saint Barnabas Medical Center
    • New York
      • Rockville Centre, New York, United States, 11570
        • Mercy Medical Center
    • North Carolina
      • Charlotte, North Carolina, United States, 28203
        • Atrium Health
    • Texas
      • Austin, Texas, United States, 78705
        • St. David's Healthcare
      • Austin, Texas, United States, 78758
        • St. David's North Austin Medical Center
      • Dallas, Texas, United States, 75231
        • Texas Health

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / 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 Names:
  • 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Ventilator-free Survival
Time Frame: Up to Day 28
Up to Day 28

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ventilator-free Days
Time Frame: Up to Day 28
Up to Day 28
Duration of Intensive Care Unit (ICU) Stay
Time Frame: Up to Day 28
Up to Day 28
Incidence of Invasive Mechanical Ventilation, ECMO and/or Death
Time Frame: Up to Day 28
Up to Day 28
Time to Death
Time Frame: Up to Day 28
Up to Day 28
All-cause Mortality
Time Frame: Day 28
Day 28
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).
Up to Day 28
Incidence of severe acute respiratory distress syndrome (ARDS)
Time Frame: Up to Day 28
Up to Day 28
Duration of Hospitalization
Time Frame: Up to Day 28
Up to Day 28
Time to Improvement in 1 or 2 Categories using 8-point Ordinal Scale
Time Frame: Up to Day 28
Up to Day 28
Number of Subjects Alive and Off Oxygen
Time Frame: Up to Day 60
Up to Day 60
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
Up to Day 60
Percentage of Participants Experiencing Serious Adverse Events
Time Frame: Up to Day 60
Using the NCI CTCAE version 5.0
Up to Day 60
Proportion of Subjects Discharged from Hospital
Time Frame: Up to Day 60
Up to Day 60
Time to improvement in oxygenation for > 48 hours
Time Frame: Up to Day 28
Up to Day 28
Incidence of Non-invasive Ventilation (or Use of High-flow Oxygen Device)
Time Frame: Up to Day 28
Up to Day 28
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)
Up to Day 28
Change from Baseline to Day 28 in Clinical status Based on the 8-point Ordinal Scale
Time Frame: Up to Day 28
Up to Day 28
Duration of Time on Low-flow or High-flow Supplemental Oxygen
Time Frame: Up to Day 28
Up to Day 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Humanigen, Inc.

Investigators

  • Study Director: Cameron Durrant, MD, Humanigen, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 5, 2020

Primary Completion (Anticipated)

March 1, 2021

Study Completion (Anticipated)

March 1, 2021

Study Registration Dates

First Submitted

April 15, 2020

First Submitted That Met QC Criteria

April 15, 2020

First Posted (Actual)

April 17, 2020

Study Record Updates

Last Update Posted (Actual)

March 3, 2021

Last Update Submitted That Met QC Criteria

March 1, 2021

Last Verified

March 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HGEN003-06

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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