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

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Trial Profile

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

Status: Completed
Phase of Trial: Phase III

Latest Information Update: 07 Mar 2023

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At a glance

  • Drugs Lenzilumab (Primary) ; Dexamethasone; Remdesivir
  • Indications COVID-19 pneumonia; Cytokine release syndrome
  • Focus Registrational; Therapeutic Use
  • Acronyms LIVE-AIR
  • Sponsors Humanigen

    • Most Recent Events

    • 06 Jul 2022 Results published in the Thorax
    • 06 Jul 2022 Results presented in a Humanigen Media Release.
    • 06 Jul 2022 According to a Humanigen media release, data from a sub-analysis of this trial published in Thorax.

Trial Overview

Outcome

Primary endpoint met - positive

Purpose

This phase III randomized, placebo-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.
Following enrollment, subjects were randomized to receive three infusions of either lenzilumab or placebo, each infusion separated by eight hours over a 24-hour period with other treatments.

Comments

According to a Humanigen media release, the company has submitted all the planned modules as well as a risk management plan and pediatric investigation plan for the lenzilumab Conditional Marketing Authorization (CMA) in hospitalized COVID-19 patients to the UK's Medicines and Healthcare Products Regulatory Agency (MHRA).
According to a Humanigen media release, compny plan to apply to MFDS for conditional approval for importation of lenzilumab for use in Korea. Support for conditional approval would be based on data from phase 1 study and the existing data from Phase 3 LIVE-AIR study. Additional clinical trials are not expected to be necessary in this situation.

According to a Humanigen media release, the company announced submission for Marketing Authorization for lenzilumab in COVID-19, begun in June 2021, has been accepted by the United Kingdoms Medicines and Healthcare Products Regulatory Agency (MHRA) for expedited COVID-related rolling review.

According to a Humanigen media release, the company has submitted an application to the US Food and Drug Administration (FDA) requesting Emergency Use Authorization (EUA) for lenzilumab for the treatment of patients hospitalized with COVID-19, based on the data from this trial.

The company also plans to submit for CMA to the EMA for the use of lenzilumab in the European Union. Further, the company is reviewing the possibility of similar submissions for approval or compassionate use in other territories or countries worldwide.

The company intends to submit a Biologics License Application (BLA) to FDA in 2022, for the use of lenzilumab in hospitalized, hypoxic COVID-19 patients.

Primary Endpoints

Met on 29 Mar 2021

Ventilator-free Survival

time_frame: Up to Day 28 [1]

Other Endpoints

Ventilator-free Days

time_frame: Up to Day 28

Duration of Intensive Care Unit (ICU) Stay

time_frame: Up to Day 28

Incidence of Invasive Mechanical Ventilation, ECMO and/or Death

time_frame: Up to Day 28

Time to Death

time_frame: Up to Day 28

All-cause Mortality

time_frame: Day 28

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

Incidence of severe acute respiratory distress syndrome (ARDS)

time_frame: Up to Day 28

Duration of Hospitalization

time_frame: Up to Day 28

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

time_frame: Up to Day 28

Number of Subjects Alive and Off Oxygen

time_frame: Up to Day 60

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

Percentage of Participants Experiencing Serious Adverse Events

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

Proportion of Subjects Discharged from Hospital

time_frame: Up to 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 [2]

Diseases Treated

Indication Qualifiers Patient Segments
COVID-19 pneumonia treatment severe
Cytokine release syndrome prevention, treatment -

Subjects

  • Subject Type patients
  • Number

    Planned: 516

    Actual: 520

  • Sex male & female
  • Age Group ≥ 18 (mean 60)years; adult; elderly

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 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

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 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

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 : 05 May 2020

  • Primary Completion Dates

    Planned : 01 Mar 2021

  • End Dates

    Planned : 01 Mar 2021

Other Details

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

Interventions

Drugs Route Formulation
Dexamethasone
-
-
LenzilumabPrimary Drug Intravenous Infusion
Remdesivir
-
-

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 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)

Results

Therapeutic efficacy

COVID-19 infections
Phase III: In phase III LIVE-AIR trial, patients with baseline CRP levels below 150 mg/L had even greater response to lenzilumab therapy, with a 62% relative reduction in the incidence of invasive mechanical ventilation or death (OR:0.38, 95%CI, 0.19-0.75, p = 0.005). Exploratory analysis of the phase III LIVE-AIR results in patients with CRP<150 mg/L and aged <85 years of age, which represented 74% of patients with an evaluable CRP at baseline, show lenzilumab improved the likelihood of survival without ventilation by more than 3-fold (OR 3.04; 95% CI: 1.68-5.51, nominal p = 0.0003) compared with placebo and mortality was improved by more than 2-fold (OR: 2.22; 95%CI: 1.07-4.67, p=0.034). Response to lenzilumab was observed in the first through third quartiles of baseline CRP with the greatest response observed in those patients treated earlier in the inflammatory process (<41 mg/L, HR:8.33; 41-<79 mg/L, HR:1.60; 79-<137 mg/L, HR: 2.12; >137 mg/L, HR: 1.17). Overall, the LIVE-AIR study achieved its primary endpoint of survival without ventilation measured through day 28 following treatment (HR: 1.54; 95%CI: 1.02-2.32, p = 0.0403) [3] . Previous results from the phase III LIVE-AIR trial in patients hospitalized with COVID-19 showed that, patients who received lenzilumab and other treatments, including steroids and/or remdesivir, had a 54% greater relative likelihood of survival without the need for invasive mechanical ventilation (IMV) compared with patients receiving placebo and other treatments achieved its primary endpoint of survival without ventilation demonstrating a 1.54-fold improvement overall and trended to a 2.68-fold improvement in Black and African-American patients (HR: 1.54; 95%CI: 1.03-2.33, p = 0.0365). Treatment with lenzilumab in patients with CRP<150 mg/L demonstrated a nearly 9-fold increase in likelihood of survival without ventilation (SWOV) [n=51, p-value=0.0412]. In the overall population with CRP<150 mg/L, lenzilumab demonstrated a 2.5-fold increased likelihood of SWOV [mITT, n=351, p-value=0.0009] [4] . Earlier results showed that the Kaplan-Meier estimate for IMV and/or death was 15.6% (95%CI: 11.5-21.0) in the lenzilumab arm versus 22.1% (95%CI: 17.4-27.9) in the placebo arm, representing a 54% improvement in the relative likelihood of survival without the need for IMV. Although this study was not powered to demonstrate a difference in mortality, a favorable trend in mortality was observed, 9.6% (95%CI: 6.4-14.2) in the lenzilumab arm compared with 13.9% (95%CI: 10.1-19.0) in the placebo arm (HR: 1.39; 95%CI: 0.82-2.39; p = 0.2287). Approximately 88% of patients received dexamethasone (or other steroids), 62% received remdesivir, and 57% received both, balanced across both arms of the study. Previous 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 [1] [5] . The LIVE-AIR study achieved its primary endpoint of survival without ventilation measured through day 28 following treatment (HR: 1.54; 95%CI: 1.02-2.32, p=0.0403). Approximately 94% of patients received dexamethasone (or other steroids), 72% received remdesivir, and 69% received both. In the subgroup of patients treated with both remdesivir and corticosteroids, lenzilumab improved survival without ventilation relative to placebo (HR: 1.92; 95%CI: 1.20-3.07, p=0.0067) [6] [7] . Lenzilumab improved SWOV by 1.91-fold (nominal p=0.0073) and 1.92-fold (nominal p=0.0067) in patients receiving remdesivir or remdesivir and corticosteroids, respectively. A key secondary endpoint of incidence of IMV, ECMO or death was also improved in patients receiving remdesivir (p=0.020) or remdesivir and corticosteroids (p=0.0180) [8]

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: Updated results from a phase III LIVE-AIR trial, lenzilumab appeared to be safe and well-tolerated. No new serious adverse events (SAEs) were identified, and none were attributed to lenzilumab. SAEs were balanced in both study arms and the SAE profile was similar to that previously documented in prior lenzilumab studies. Previous results from 12 patients showed no reported mortality. No treatment-emergent adverse events attributable to lenzilumab was observed and it was well-tolerated [1] [5] [6] . Treatment with lenzilumab resulted in no serious infusion-related reactions, no increase in the incidence of secondary infections and no attributable serious adverse events, including, hematologic or liver enzyme abnormalities. In addition, no cases of pulmonary alveolar proteinosis were reported. The incidence of treatment-emergent serious adverse events was similar across treatment groups [7] .

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.

Pharmacodynamics

In phase-III LIVE-AIR trial, lenzilumab significantly reduced circulating cytokines and markers of systemic inflammation in patient with COVID-2019 infections. granulocyte-macrophage colony-stimulating factor (GM-CSF) levels decreased with lenzilumab treatment on day 1 (D1) which persisted through D10. In contrast, GM-CSF increased with placebo treatment. IL-6 levels decreased only with lenzilumab treatment. C-reactive protein (CRP) following lenzilumab or placebo treatment decreased on D1 to similar levels and further decreased on D10 only with lenzilumab treatment [9] .

Publications

  1. Humanigen. Humanigen Reports Positive Phase 3 Topline Results Demonstrating That Lenzilumab(Tm) Improves Survival Without Need for Mechanical Ventilation in Hospitalized Patients With COVID-19. Media-Rel 2021;.

    Media Release

  2. Humanigen. Humanigen Announces Late-Breaking Presentation at the CHEST Annual Meeting Highlighting C-Reactive Protein as a Biomarker for Identifying Patients Most Likely to Benefit from treatment with Lenzilumab. Media-Rel 2021;.

    Media Release

  3. Humanigen. Lenzilumab Treatment May Provide Enhanced Likelihood of Survival Without Ventilation in Hospitalized Black and African-American COVID-19 Patients. Media-Rel 2021;.

    Media Release

  4. 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

  5. Humanigen. Humanigen Announces Oral Presentation of Lenzilumab LIVE-AIR Phase 3 Study Results at IDWeek 2021. Media-Rel 2021;.

    Media Release

  6. Humanigen. Humanigen Announces Abstracts Accepted for the British Thoracic Society Winter Meeting 2021. Media-Rel 2021;.

    Media Release

  7. Temesgem Z, Burger C, Baker J, Polk C, Libertin CR, Kelley CF, et al. Lenzilumab Efficacy and Safety in Newly Hospitalized COVID-19 Subjects: Results From a Phase 3 Randomized Double-Blind Placebo-Controlled Trial. IDW-2021 2021; abstr. 40.

    Available from: URL: https://academic.oup.com/ofid/article/8/Supplement_1/S29/6449617

  8. Chappell D, Kilcoyne A, Cerasoli F, Lukas J, Durrant C, Temesgen Z, et al. Lenzilumab Treatment in COVID-19 Pneumonia Reduces Circulating Cytokines and Markers of Systemic Inflammation. IDW-2022 2022; abstr. 1134.

    Available from: URL: https://academic.oup.com/ofid/article/9/Supplement_2/ofac492.973/6902879

  9. Humanigen. Humanigen Announces Positive Interim Phase 3 Data of Lenzilumab(Tm) in Patients Hospitalized with COVID-19. Media-Rel 2020;.

    Media Release

  10. Humanigen. Lenzilumab Treatment Response in Hospitalized COVID-19 Patients Correlates with C-Reactive Protein Levels. Media-Rel 2022;.

    Media Release

  11. Humanigen. European Commission Selects Humanigens Lenzilumab as One of the 10 Most Promising Treatments for COVID-19. Media-Rel 2021;.

    Media Release

  12. Temesgen Z, Kelley CF, Cerasoli F, Kilcoyne A, Chappell D, Durrant C, et al. C reactive protein utilisation, a biomarker for early COVID-19 treatment, improves lenzilumab efficacy: results from the randomised phase 3 'LIVE-AIR' trial. . Thorax 2022;.

    PubMed | CrossRef Fulltext

  13. Humanigen. The Lancet Respiratory Medicine Publishes Peer-Reviewed Paper and Independent Expert Commentary on Positive Phase 3 Lenzilumab Results. Media-Rel 2021;.

    Media Release

  14. Temesgen Z, Burger C, Baker J, Polk C, Libertin C, Kelley C, et al. C-Reactive Protein as a Biomarker for Improved Efficacy of Lenzilumab in Patients with Covid-19: Results from the Live-Air Trial. CHEST-2021 2021; abstr. N/A.

    Available from: URL: https://journal.chestnet.org/article/S0012-3692(21)03654-0/fulltext

  15. Humanigen. Humanigen Announces Peer-Reviewed Publication in Thorax Supporting Early Treatment of Hospitalized COVID-19 Patients with Lenzilumab Guided by C-Reactive Protein. Media-Rel 2022;.

    Media Release

Authors

Author Total Publications First Author Last Author
Ahmed O 3 - -
Aronstein W 2 - -
Badley A 3 - 1
Baker J 3 - -
Burger C 2 - -
Catterson V 3 - -
Cerasoli F 2 - -
Chappell D 4 1 -
Chappell G 3 - -
Durrant C 4 - -
for the LIVE-AIR Study Group 1 - 1
Humanigen 10 10 10
Kelley C 1 - -
Kelley CF 2 - -
Kilcoyne A 2 - -
Libertin C 1 - -
Libertin CR 1 - -
Lukas J 1 - -
Marconi V 3 - 1
Marconi VC 1 - 1
Mayo Clinic 1 1 1
Orenstein R 2 - -
Polk C 4 - -
Temesgem Z 1 1 -
Temesgen Z 3 2 -

Trial Centres

Investigators

Download Data (CSV)
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
-
Omar Ahmed, PharmD
201-509-0713
oahmed@humanigen.com
show details 		, Humanigen, Inc.
-

+ Lead investigator

Centres

Download Data (CSV)
Centre Name Location Trial Centre Country
-
-
-
AdventHealth Orlando Orlando, Florida USA
Atrium Health Charlotte, North Carolina USA
CEMEC - Centro Multidisciplinar de Estudos Clínicos LTDA-EPP São Bernardo do Campo, São Paulo Brazil
Clinica de Alergia Martti Antila S/S LTDA Sorocaba, São Paulo Brazil
CPCLIN - Centro de Pesquisas Clínicas de Natal Natal, Rio Grande Do Norte Brazil
Dartmouth-Hitchcock Lebanon, New Hampshire USA
Emory University Atlanta, Georgia USA
Escola Paulista de Medicina (UNIFESP) São Paulo Brazil
Hennepin County Medical Center Minneapolis, Minnesota USA
Hospital Dia do Pulmão Blumenau, São Paulo Brazil
Hospital Guilherme Alvaro Santos, São Paulo Brazil
Hospital Heliópolis São Paulo Brazil
Hospital São Lucas - PUCRS Porto Alegre, Rio Grande Do Sul Brazil
Hospital São Luiz do Jabaquara/IDOR São Paulo Brazil
Hospital Vera Cruz Belo Horizonte, Minas Gerais Brazil
Humanigen, Inc.
-
-
Humanigen, Inc.
-
-
Mayo Clinic Jacksonville, Florida USA
Mayo Clinic Phoenix, Arizona USA
Mayo Clinic Rochester, Minnesota USA
MedStar Washington Hospital Center Washington, District of Columbia USA
Mercy Medical Center Rockville Centre, New York USA
Saint Barnabas Medical Center Livingston, New Jersey USA
Sociedade Literaria e Caritativa Santo Agostinho Criciúma, Santa Catarina Brazil
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 California, Irvine Irvine, California USA
University of Southern California (USC) Medical Center Los Angeles, California USA
USC - Los Angeles County Medical Center Los Angeles, California USA

+ Lead Centre

Show all rows

Trial History

Event Date Event Type Comment
07 Mar 2023 Other trial event According to ClinicalTrials.gov, the recruitment status of this study is unknown because the information has not been verified recently (last verified March 2021). Updated 07 Mar 2023
07 Mar 2023 Other trial event Last checked against ClinicalTrials.gov record. Updated 07 Mar 2023
23 Oct 2022 Results Results of sub-analysis assessing levels of cytokines before and after lenzilumab treatment, presented at the IDWeek 2022. Updated 03 Feb 2023
06 Jul 2022 Results Results published in the Thorax Updated 13 Jul 2022
06 Jul 2022 Results Results presented in a Humanigen Media Release. Updated 11 Jul 2022
06 Jul 2022 Results According to a Humanigen media release, data from a sub-analysis of this trial published in Thorax. Updated 11 Jul 2022
03 Jan 2022 Results Results of an analysis of CRP levels published in the Humanigen Media Release. Updated 05 Jan 2022
01 Dec 2021 Other trial event According to a Humanigen media release, results of the trial has been published in a lancet peer-reviewed journal and an independent expert commentary. Updated 10 Jan 2022
01 Dec 2021 Results Results published in the Media Release Updated 10 Dec 2021
22 Nov 2021 Results According to a Humanigen media release, data from this trial was presented at the British Thoracic Society Winter 2021 Updated 06 Dec 2021
22 Nov 2021 Results Results published in the Humanigen Media Release. Updated 06 Dec 2021
25 Oct 2021 Results Results from the Live-Air Trial published in the Humanigen Media Release Updated 23 Dec 2021
25 Oct 2021 Other trial event According to a Humanigen media release, results of the trial have been submitted for publication in a peer-reviewed journal Updated 28 Oct 2021
20 Oct 2021 Results Results presented at the CHEST Annual Meeting 2021 by Annual Meeting of the American College of Chest Physicians Updated 23 Dec 2021
19 Oct 2021 Results Results published in the Humanigen Media Release. Updated 26 Oct 2021
19 Oct 2021 Results According to a Humanigen media release, results from this trial has been published in the journal CHEST. Updated 26 Oct 2021
19 Oct 2021 Other trial event According to a Humanigen media release, results from this trial will be presented at the CHEST Annual Meeting 2021, which is being hosted by the American College of Chest Physicians (CHEST) virtually. Updated 26 Oct 2021
04 Oct 2021 Other trial event According to a Humanigen media release, data from this trial will be presented at The International Cytokine & Interferon Society (ICIS), during the Exhibitor Breaking News Session virtual meeting platform. Updated 07 Oct 2021
03 Oct 2021 Results Results assessing the efficacy and safety of lenzilumab to improve the likelihood of survival without invasive mechanical ventilation, presented at the IDWeek 2021. Updated 05 Feb 2022
01 Oct 2021 Other trial event According to a Humanigen media release, the company has submitted all the planned modules as well as a risk management plan and pediatric investigation plan for the lenzilumab Conditional Marketing Authorization (CMA) in hospitalized COVID-19 patients to the UK's Medicines and Healthcare Products Regulatory Agency (MHRA). Updated 07 Oct 2021
29 Sep 2021 Other trial event According to a Humanigen media release, results from the study have been submitted for publication in a peer-reviewed journal. Updated 01 Oct 2021
29 Sep 2021 Results Results published in the Humanigen Media Release. Updated 01 Oct 2021
29 Sep 2021 Other trial event According to a Humanigen media release, results from the study will be presented at IDWeek 2021, which is the joint annual meeting of the IDSA, the Society for Healthcare Epidemiology of America (SHEA), the HIV Medical Association (HIVMA), the Pediatric Infectious Diseases Society (PIDS), and the Society of Infectious Diseases Pharmacists (SIDP). Updated 01 Oct 2021
28 Sep 2021 Other trial event According to a Humanigen media release, the company plans to submit an MAA under the centralized procedure seeking Conditional Marketing Authorization (CMA) throughout the European Union (EU) for the use of lenzilumab to treat patients hospitalized with COVID-19 pneumonia. The company expects to request accelerated assessment. the European Medicines Agency (EMA) has appointed a rapporteur and a co-rapporteur as part of the pre-submission process related to the plan to submit an MAA. Updated 01 Oct 2021
04 Aug 2021 Other trial event According to a Humanigen media release, the company intends to submit data from this analysis for publication in a peer-reviewed journal and present the findings at a medical meeting. Updated 09 Aug 2021
04 Aug 2021 Results Results (n=51) presented in a Humanigen media release. Updated 09 Aug 2021
22 Jul 2021 Other trial event According to a Humanigen media release, compny plan to apply to MFDS for conditional approval for importation of lenzilumab for use in Korea. Support for conditional approval would be based on data from phase 1 study and the existing data from Phase 3 LIVE-AIR study. Additional clinical trials are not expected to be necessary in this situation. Updated 27 Jul 2021
09 Jul 2021 Other trial event According to a Humanigen media release, the company announced submission for Marketing Authorization for lenzilumab in COVID-19, begun in June 2021, has been accepted by the United Kingdoms Medicines and Healthcare Products Regulatory Agency (MHRA) for expedited COVID-related rolling review. Updated 13 Jul 2021
14 Jun 2021 Other trial event According to a Humanigen media release, the company has initiated a rolling review submission for Lenzilumab marketing authorization in COVID-19 to the United Kingdoms Medicines and Healthcare Products Regulatory Agency (MHRA), based on data from this trial. Updated 17 Jun 2021
28 May 2021 Other trial event According to a Humanigen media release, the company has submitted an application to the US Food and Drug Administration (FDA) requesting Emergency Use Authorization (EUA) for lenzilumab for the treatment of patients hospitalized with COVID-19, based on the data from this trial. Updated 02 Jun 2021
13 May 2021 Other trial event According to a Humanigen media release, the company intends to submit a Biologics License Application (BLA) to FDA in 2022, for the use of lenzilumab in hospitalized, hypoxic COVID-19 patients. Updated 19 May 2021
13 May 2021 Other trial event According to a Humanigen media release, the company recently held a meeting with FDA to discuss the filing of an EUA for lenzilumab for hospitalized, hypoxic COVID-19 patients, where topline data from this study were reviewed, along with the timeline for submission of additional clinical and manufacturing data for lenzilumab. The company plans to submit an EUA application at the end of May 2021 Updated 19 May 2021
13 May 2021 Other trial event According to a Humanigen media release, the company plans to initiate a rolling CMA submission with the MHRA for the use of lenzilumab in COVID-19 patients in the UK before the end of the second quarter of 2021. The company also plans to submit for CMA to the EMA for the use of lenzilumab in the European Union. Further, the company is reviewing the possibility of similar submissions for approval or compassionate use in other territories or countries worldwide. Updated 19 May 2021
05 May 2021 Results According to a Humanigen media release, results from this study has been published on-line ( Link : https://www.medrxiv.org/content/10.1101/2021.05.01.21256470v1.full.pdf) . Updated 09 May 2021
19 Apr 2021 Status change - completed According to a Humanigen media release, Status changed from active, no longer recruiting to completed. Updated 22 Apr 2021
29 Mar 2021 Other trial event According to a Humanigen media release, the company will host a conference call and webcast to discuss topline results from this trial. Updated 06 Apr 2021
29 Mar 2021 Other trial event According to a Humanigen media release, Zelalem Temesgen, MD, Professor of Medicine at Mayo Clinic is principal investigator for this study. Updated 31 Mar 2021
29 Mar 2021 Endpoint met According to a Humanigen media release, primary endpoint (Ventilator-free Survival) has been met. Updated 31 Mar 2021
29 Mar 2021 Results Results presented in a Humanigen Media Release. Updated 31 Mar 2021
29 Mar 2021 Other trial event According to a Humanigen media release, the results from this trial are planned to be submitted for potential publication in a peer-reviewed journal. Updated 31 Mar 2021
25 Feb 2021 Other trial event According to a Humanigen media release, data from this study will be presented at the H.C. Wainwright Global Life Sciences Conference being held from March 9-10, 2021, the Roth Conference being held from March 15-17, 2021, and the Oppenheimer Annual Healthcare Conference being held from March 16-17, 2021. Updated 02 Mar 2021
29 Jan 2021 Other trial event According to a Humanigen media release, top-line data from this trial is expected in March 2021. Updated 02 Feb 2021
29 Jan 2021 Status change - active, no longer recruiting Status changed from recruiting to active, no longer recruiting according to a Humanigen media release Updated 02 Feb 2021
19 Jan 2021 Protocol amendment Time Frame changed to Up to Day 28. Planned number of patients increased. Updated 27 Jan 2021
19 Jan 2021 Other trial event Planned number of patients changed from 300 to 516. Updated 27 Jan 2021
19 Jan 2021 Completion date Planned End Date changed from 1 Sep 2020 to 1 Mar 2021. Updated 27 Jan 2021
19 Jan 2021 Other trial event Planned primary completion date changed from 1 Sep 2020 to 1 Mar 2021. Updated 27 Jan 2021
05 Jan 2021 Other trial event According to a Humanigen media release, update on the enrollment of this study will be presented at the H.C. Wainwright BioConnect Conference, J.P. Morgan Healthcare Conference and 23rd Annual ICR Conference being held virtually between January 11-14, 2021. Updated 08 Jan 2021
17 Dec 2020 Other trial event According to a Humanigen media release, the company will provide an update on enrollment for this study at the J.P. Morgan Healthcare Conference. Updated 24 Dec 2020
06 Nov 2020 Other trial event According to a Humanigen media release, CRADA between Humanigen and U.S. government provides for regulatory and other support to submit an EUA and BLA. Updated 17 Nov 2020
06 Nov 2020 Other trial event According to a Humanigen media release, the company intends to file for EUA in the first quarter of 2021 either following interim data at 75 percent or at study completion.Current enrollment stands at 300 patients. Updated 17 Nov 2020
06 Nov 2020 Other trial event According to a Humanigen media release, at the recommendation of the DSMB, the company plans to increase enrollment to achieve 402 events (approximately 515 patients).This increase in enrollment ensures an even higher probability of success in meeting the primary endpoint and maintains the power of the study at 90 %. The next interim analysis for efficacy is planned when the study reaches 75 percent events (302 events) which will require approximately 390 patients to be enrolled in the trial. Updated 17 Nov 2020
06 Nov 2020 Other trial event According to a Humanigen media release, the data safety monitoring board (DSMB) conducted an interim analysis of the unblinded data for trial sizing and powering and recommended increasing the target number of events (recoveries) from 257 to 402 to maintain the power of the study at 90 percent. Data safety monitoring board recommendation demonstrates the Phase 3 trial is in the promising zone of the adaptive trial design. Updated 17 Nov 2020
06 Nov 2020 Other trial event According to a Humanigen media release, the Company will host an investor call and webcast today at 9:00 a.m. EST to discuss the interim results. Updated 17 Nov 2020
06 Nov 2020 Interim results Interim analysis results presented in a Humanigen media release. Updated 17 Nov 2020
30 Oct 2020 Other trial event According to a Humanigen media release, MedStar Washington Hospital Center is one of 18 sites in the U.S. approved to enroll eligible patients to study lenzilumab, designed specifically to stop this storm. Updated 04 Nov 2020
30 Oct 2020 Other trial event According to a Humanigen media release, the first patient has been dosed in this trial. Updated 04 Nov 2020
02 Oct 2020 Other trial event According to a Humanigen media release, the FDA provided feedback on the Company's Chemistry, Manufacturing and Controls (CMC) plan, EUA labelling and the Statistical Analysis Plan (SAP) and agreed that no material changes are needed across these elements. Updated 12 Oct 2020
02 Oct 2020 Other trial event According to a Humanigen media release, the company has received a written guidance from the US Food and Drug Administration (FDA) following a Type B meeting to obtain feedback on plans for an Emergency Use Authorization (EUA). FDA agreed that the Company's intended submission may be sufficient to support an EUA request, subject to Phase 3 trial data, and provided guidance and support for the Company's Biologics License Application and approval pathway. Updated 12 Oct 2020
02 Oct 2020 Other trial event According to a Humanigen media release, The Mexican regulatory agency, COFEPRIS, has granted permission to commence a Phase 3 study of lenzilumab in patients with COVID-19 in Mexico. Clinical trial sites are being activated to initiate patient enrollment in the study, which will follow the same protocol that was approved by the FDA and is running in the sites in US and Brazil; the data from all sites to be aggregated for Phase 3 purposes. Updated 09 Oct 2020
02 Oct 2020 Other trial event According to a Humanigen media release, Seven of the 12 approved trial sites in Brazil are currently validated to begin enrolling patients. Several patients have been dosed across multiple sites in Brazil in four of the seven centers now enrolling patients. Program clinical trial investigators in Brazil stressed the importance of this program and urgency for enrollment during a recent investigator meeting. Updated 09 Oct 2020
02 Oct 2020 Other trial event According to a Humanigen media release, the trial is continuing to enroll in the U.S. and Brazil, and now has been approved to expand to Mexico. The trial currently has a total of 29 approved sites with 24 actively enrolling hospitalized adult COVID-19 patients who require supplemental oxygen and are at high risk of disease progression. 17 trial sites are active in the US. Updated 09 Oct 2020
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
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

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