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

Trial Profile

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

Status: Recruiting
Phase of Trial: Phase III

Latest Information Update: 14 Sep 2020

At a glance

  • Drugs Lenzilumab (Primary)
  • Indications Adult respiratory distress syndrome; COVID 2019 infections; Pneumonia; Respiratory insufficiency
  • Focus Registrational; Therapeutic Use
  • Sponsors Humanigen
  • Most Recent Events

    • 14 Sep 2020 According to a Humanigen media release, enrollment target of 300 patients expected to be completed this month with topline data available in the fourth quarter.
    • 14 Sep 2020 According to a Humanigen media release, an Independent data safety monitoring board (DSMB) unanimously recommended trial continuation without modification after conducting pre-specified interim analysis for safety, futility, sample size and power. A pre-specified interim analysis was conducted after 50% of the expected recoveries were captured in the trial database.
    • 01 Sep 2020 According to a Humanigen media release, this trial was selected by the National Institutes of Health for its COVID-19 Big Effect Trial.

Trial Overview

Purpose

This phase III randomized, controlled, multi-center study is designed to evaluate Lenzilumab for the prevention of respiratory failure/ARDS and/or death in hospitalized patients with pneumonia associated with SARS-CoV-2 infection in COVID-19 patients.The study enrollment will focus on adult, hospitalized patients with COVID-19 pneumonia and at high risk of progression to respiratory failure.
Patients will be randomized to receive lenzilumab + SOC vs. SOC in a 1:1 ratio. An interim analysis is planned for DSMB to assess safety & efficacy data.

Comments

According to a Humanigen media release, if successful, this study may lead to a lenzilumab product approval for COVID-19.

Primary Endpoints

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 28 days

Other Endpoints

Incidence of Invasive Mechanical Ventilation and/or Death

time_frame: Up to 28 days

Incidence of severe acute respiratory distress syndrome (ARDS)

time_frame: Up to 28 days

Duration of Intensive Care Unit (ICU) Stay

time_frame: Up to 28 days

Ventilator-free Days

time_frame: Up to 60 days

Duration of Hospitalization

time_frame: Up to 28 days

Time to Improvement in 1 or 2 Categories using 8-point Ordinal Scale

time_frame: Up to Day 28

Time to Death

time_frame: Up to Day 28

Number of Subjects Alive and Off Oxygen

time_frame: Up to 60 days

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 60 days

Percentage of Participants Experiencing Serious Adverse Events

description: Using the NCI CTCAE version 5.0
time_frame: Up to 60 days

Proportion of Subjects Discharged from Hospital

time_frame: Up to Day 60

All-cause Mortality and Proportion of Subjects Alive

time_frame: Day 28 and Day 60

Time to improvement in oxygenation for > 48 hours

time_frame: Up to Day 28

Incidence of Non-invasive Ventilation (or Use of High-flow Oxygen Device)

time_frame: Up to Day 28

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

Change from Baseline to Day 28 in Clinical status Based on the 8-point Ordinal Scale

time_frame: Up to Day 28

Duration of Time on Low-flow or High-flow Supplemental Oxygen

time_frame: Up to Day 28 [1]

Diseases Treated

Indication Qualifiers Patient Segments
Adult respiratory distress syndrome prevention -
COVID 2019 infections treatment -
Pneumonia treatment severe
Respiratory insufficiency prevention -

Subjects

  • Subject Type patients
  • Number

    Planned: 300

  • Sex male & female
  • Age Group ≥ 18 years; adult

Patient 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 supplemental oxygen (including high-flow oxygen support or NPPV) - 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

Patient 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 approved anti-IL-6 (e.g., tocilizumab, sarilumab, sitlukimab), anti-IL-1 (e.g., anakinra, canakinumab) or kinase inhibitor (e.g., baracitinib, ibrutinib, acalabrutinib) 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 < 24h 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

Trial Details

Identifiers

Identifier Owner
NCT04351152 ClinicalTrials.gov: US National Institutes of Health
HGEN003-06 -

Organisations

  • Sponsors Humanigen
  • Affiliations Catalent; Humanigen

Trial Dates

  • Initiation Dates

    Planned : 01 May 2020

    Actual : 30 Apr 2020

  • Primary Completion Dates

    Planned : 01 Sep 2020

  • End Dates

    Planned : 01 Sep 2020

Other Details

  • Design double-blind; multicentre; parallel; prospective; randomised
  • Phase of Trial Phase III
  • Location USA
  • Focus Registrational; Therapeutic Use

Interventions

Drugs Route Formulation
LenzilumabPrimary Drug Intravenous Infusion

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 per local written policies or guidelines)

Placebo Arm

Participants will receive IV infusion of saline 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 per local written policies or guidelines)

Results

Therapeutic efficacy

COVID-19 infections
Phase III
: Results from 12 patients showed rapid clinical improvement with a median time to recovery of five days, median time to discharge of five days with 11 of them discharged from the hospital and 100% survival to the data cut-off date. Patients also demonstrated rapid improvement in oxygenation, temperature, inflammatory cytokines and key hematological parameters consistent with improved clinical outcomes [2] .

Disease stabilisation was observed in 12/13 evaluable patients with metastatic prostate cancer after treatment with liarozole. The median time to progression was 34 weeks. Of four patients with measurable disease, three showed a decrease in tumour size (> 50% reduction in one patient and < 50% reduction in the other two patients). Relief from bone pain was experienced by 5/9 evaluable patients within 2 weeks. Reductions in PSA levels were observed in seven patients.

Adverse events

COVID-19 infections
Phase III
: Results from 12 patients showed no reported mortality. No treatment-emergent adverse events attributable to lenzilumab was observed and it was well-tolerated [2] .

Cutaneous disorders, similar to those associated with excess levels of retinoic acid, were the most frequently reported adverse events associated with liarozole and may be associated with its retinoid-sparing activity. Dermatological adverse events, most commonly itching, rash, brittle nails, and dry skin and lips, were reported in all clinical trials with liarozole.

Publications

  1. Mayo Clinic. Mayo Clinic Study of Humanigens Lenzilumab Shows Rapid Recovery and Discharge in Severe and Critical COVID-19 Patients. Media-Rel 2020;.

    Media Release

Authors

Author Total Publications First Author Last Author
Mayo Clinic 1 1 1

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
Cameron Durrant, MD Humanigen, Inc.
-
CTI Clinical Trial & Consulting Services (CRO)
513-598-9290 HumanigenPhase3@ctifacts.com
show details
-
M Center USC - Los Angeles County Medical Center USA
Omar Ahmed, PharmD
201-509-0713
oahmed@humanigen.com
show details
, Humanigen, Inc.
-

Centres

Centre Name Location Trial Centre Country
-
-
-
AdventHealth Orlando Orlando, Florida USA
Atrium Health Charlotte, North Carolina USA
Baptist Medical Center Jacksonville, Florida USA
Dartmouth-Hitchcock Lebanon, New Hampshire USA
Emory University Atlanta, Georgia USA
Hennepin County Medical Center Minneapolis, Minnesota USA
Humanigen, Inc.
-
-
Humanigen, Inc.
-
-
Mayo Clinic Jacksonville, Florida USA
Mayo Clinic Phoenix, Arizona USA
Mayo Clinic Rochester, Minnesota USA
Saint Barnabas Medical Center Livingston, New Jersey USA
St. David's Healthcare Austin, Texas USA
St. David's North Austin Medical Center Austin, Texas USA
St. Elizabeth Healthcare Edgewood, Kentucky USA
Texas Health Dallas, Texas USA
University of Southern California (USC) Medical Center Los Angeles, California USA
USC - Los Angeles County Medical Center Los Angeles, California USA

Trial History

Event Date Event Type Comment
14 Sep 2020 Other trial event According to a Humanigen media release, enrollment target of 300 patients expected to be completed this month with topline data available in the fourth quarter. Updated 16 Sep 2020
14 Sep 2020 Other trial event According to a Humanigen media release, an Independent data safety monitoring board (DSMB) unanimously recommended trial continuation without modification after conducting pre-specified interim analysis for safety, futility, sample size and power. A pre-specified interim analysis was conducted after 50% of the expected recoveries were captured in the trial database. Updated 16 Sep 2020
01 Sep 2020 Other trial event According to a Humanigen media release, this trial was selected by the National Institutes of Health for its COVID-19 Big Effect Trial. Updated 08 Sep 2020
06 Aug 2020 Other trial event Last checked against ClinicalTrials.gov record. Updated 06 Aug 2020
03 Aug 2020 Other trial event Planned number of patients changed from 238 to 300. Updated 06 Aug 2020
16 Jul 2020 Other trial event According to a Humanigen media release, the company expands partnership with Catalent Biologics under which Catalent will provide development, manufacturing and commercialization services for lenzilumab. Under the expanded partnership, Catalent is providing clinical supply support for this trial from its Philadelphia facility. Updated 23 Jul 2020
15 Jun 2020 Other trial event According to a Mayo Clinic media release, Dr. Zelalem Temesgen, Professor of Medicine at Mayo Clinic is one of the key authors of the study. Updated 03 Sep 2020
15 Jun 2020 Interim results According to a Mayo Clinic media release, Interim data (n=12) was published online at medRxiv.org Updated 19 Jun 2020
15 Jun 2020 Interim results Interim results (n=12) presented in a Mayo Clinic Media Release. Updated 19 Jun 2020
06 May 2020 Other trial event According to a Humanigen media release, first COVID-19 patient has been dosed in the study. Updated 11 May 2020
30 Apr 2020 Status change - recruiting Status changed from not yet recruiting to recruiting. Updated 05 May 2020
20 Apr 2020 Other trial event New source identified and integrated (ClinicalTrials.gov: US National Institutes of Health; NCT04351152) Updated 20 Apr 2020
15 Apr 2020 Other trial event According to a Humanigen media release, if successful, this study may lead to a lenzilumab product approval for COVID-19. Updated 21 Apr 2020
15 Apr 2020 Other trial event According to a Humanigen media release, the company is working with some of the top centers and clinicians in the US, alongside the contract research organization partner, CTI, to bring lenzilumab rapidly through this clinical study which, if successful, may reduce serious and potentially fatal outcomes in patients hospitalized with COVID-19 and at high risk of progression. Updated 21 Apr 2020
15 Apr 2020 Other trial event According to a Humanigen media release, the FDA has given permission to commence this Phase III study of lenzilumab in patients with COVID-19.The company will begin enrolling patients as soon as possible at several leading centers. Updated 21 Apr 2020
15 Apr 2020 Status change - not yet recruiting Status changed from planning to not yet recruiting. Updated 20 Apr 2020
03 Apr 2020 New trial record New trial record Updated 03 Apr 2020
27 Mar 2020 Other trial event According to a Humanigen media release, the company has submitted an initial protocol synopsis to FDA for this trial. Updated 03 Apr 2020

References

  1. ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2016;.

    Available from: URL: http://clinicaltrials.gov
  2. Mayo Clinic. Mayo Clinic Study of Humanigens Lenzilumab Shows Rapid Recovery and Discharge in Severe and Critical COVID-19 Patients. Media-Rel 2020;.

    Media Release
  3. Humanigen. Humanigen Submits Phase III Protocol Synopsis to FDA for Lenzilumab for Coronavirus Treatment. Media-Rel 2020;.

    Media Release
  4. GM-CSF Neutralization With Lenzilumab in Severe COVID-19 Pneumonia: A Case-Control Study. Internet-Doc 2020;.

    Available from: URL: https://www.sciencedirect.com/science/article/pii/S0025619620309897
  5. Humanigen. FDA Approves Initiation of Humanigen's Phase III Study of Lenzilumab in COVID-19 Patients. Media-Rel 2020;.

    Media Release
  6. Humanigen. Lenzilumab COVID-19 Case-Control Study Published in Mayo Clinic Proceedings Journal. Media-Rel 2020;.

    Media Release
  7. Humanigen. First Patient Dosed in FDA-Approved Phase III Lenzilumab Study for COVID-19. Media-Rel 2020;.

    Media Release
  8. Humanigen. Humanigen Expands Partnership with Catalent Biologics to Manufacture Investigational COVID-19 Therapeutic Candidate Lenzilumab. Media-Rel 2020;.

    Media Release
  9. Humanigen. Humanigen Announces Review of Lenzilumab Phase 3 Study in COVID-19 by Data Safety Monitoring Board. Media-Rel 2020;.

    Media Release
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