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

NCT ID: NCT04351152

Last Updated: 2021-03-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

520 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-05-05

Study Completion Date

2021-03-31

Brief Summary

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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

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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.

Conditions

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Coronavirus Disease 2019 (COVID-19) Pneumonia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators
Double-Blind

Study Groups

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Lenzilumab Arm

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

Group Type EXPERIMENTAL

Lenzilumab

Intervention Type BIOLOGICAL

Administered as an intravenous (IV) infusion

Standard of Care

Intervention Type DRUG

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

Group Type PLACEBO_COMPARATOR

Standard of Care

Intervention Type DRUG

Standard of care therapy can include remdesivir and/or dexamethasone per institutional treatment guidelines or written policies

Interventions

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Lenzilumab

Administered as an intravenous (IV) infusion

Intervention Type BIOLOGICAL

Standard of Care

Standard of care therapy can include remdesivir and/or dexamethasone per institutional treatment guidelines or written policies

Intervention Type DRUG

Other Intervention Names

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Humaneered® anti-human GM-CSF monoclonal Antibody

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Humanigen, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Cameron Durrant, MD

Role: STUDY_DIRECTOR

Humanigen, Inc.

Locations

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Mayo Clinic

Phoenix, Arizona, United States

Site Status

University of California, Irvine

Irvine, California, United States

Site Status

University of Southern California (USC) Medical Center

Los Angeles, California, United States

Site Status

USC - Los Angeles County Medical Center

Los Angeles, California, United States

Site Status

MedStar Washington Hospital Center

Washington D.C., District of Columbia, United States

Site Status

Mayo Clinic

Jacksonville, Florida, United States

Site Status

AdventHealth Orlando

Orlando, Florida, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

St. Elizabeth Healthcare

Edgewood, Kentucky, United States

Site Status

Hennepin County Medical Center

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Dartmouth-Hitchcock

Lebanon, New Hampshire, United States

Site Status

Saint Barnabas Medical Center

Livingston, New Jersey, United States

Site Status

Mercy Medical Center

Rockville Centre, New York, United States

Site Status

Atrium Health

Charlotte, North Carolina, United States

Site Status

St. David's Healthcare

Austin, Texas, United States

Site Status

St. David's North Austin Medical Center

Austin, Texas, United States

Site Status

Texas Health

Dallas, Texas, United States

Site Status

Hospital Vera Cruz

Belo Horizonte, Minas Gerais, Brazil

Site Status

CPCLIN - Centro de Pesquisas Clínicas de Natal

Natal, Rio Grande do Norte, Brazil

Site Status

Hospital São Lucas - PUCRS

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Sociedade Literaria e Caritativa Santo Agostinho

Criciúma, Santa Catarina, Brazil

Site Status

Hospital Dia do Pulmão

Blumenau, São Paulo, Brazil

Site Status

Hospital Guilherme Alvaro

Santos, São Paulo, Brazil

Site Status

CEMEC - Centro Multidisciplinar de Estudos Clínicos LTDA-EPP

São Bernardo do Campo, São Paulo, Brazil

Site Status

Clinica de Alergia Martti Antila S/S LTDA

Sorocaba, São Paulo, Brazil

Site Status

Escola Paulista de Medicina (UNIFESP)

São Paulo, , Brazil

Site Status

Hospital Heliópolis

São Paulo, , Brazil

Site Status

Hospital São Luiz do Jabaquara/IDOR

São Paulo, , Brazil

Site Status

Countries

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United States Brazil

References

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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.

Reference Type DERIVED
PMID: 35793833 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34863332 (View on PubMed)

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 [Preprint]. 2021 May 5:2021.05.01.21256470. doi: 10.1101/2021.05.01.21256470.

Reference Type DERIVED
PMID: 33972949 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33673929 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33153629 (View on PubMed)

Other Identifiers

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HGEN003-06

Identifier Type: -

Identifier Source: org_study_id

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