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

NCT04351152 | Unknown Phase 3 DMC FDA Drug

• 1 other identifier: HGEN003-06
• Study Type: interventional
• Target: 520
• Locations: 2 countries
• Sites: 29

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Ventilator-free Survival

  Up to Day 28

Secondary Outcomes (18)

• Ventilator-free Days

  Up to Day 28

• Duration of Intensive Care Unit (ICU) Stay

  Up to Day 28

• Incidence of Invasive Mechanical Ventilation, ECMO and/or Death

  Up to Day 28

• Time to Death

  Up to Day 28

• All-cause Mortality

  Day 28

Study Arms (2)

Lenzilumab Arm

EXPERIMENTAL

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

Biological: Lenzilumab; Drug: Standard of Care

Placebo Arm

PLACEBO COMPARATOR

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

Interventions

Lenzilumab BIOLOGICAL

Administered as an intravenous (IV) infusion

Also known as: Humaneered® anti-human GM-CSF monoclonal Antibody

Lenzilumab Arm

Standard of Care DRUG

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

Lenzilumab Arm; Placebo Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Humanigen, Inc.: lead

Study Sites (29)

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

University of California, Irvine

Irvine, California, 92697, United States

Location

University of Southern California (USC) Medical Center

Los Angeles, California, 90033, United States

Location

USC - Los Angeles County Medical Center

Los Angeles, California, 90033, United States

Location

MedStar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

Mayo Clinic

Jacksonville, Florida, 32216, United States

Location

AdventHealth Orlando

Orlando, Florida, 32803, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

St. Elizabeth Healthcare

Edgewood, Kentucky, 41017, United States

Location

Hennepin County Medical Center

Minneapolis, Minnesota, 55415, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Dartmouth-Hitchcock

Lebanon, New Hampshire, 03756, United States

Location

Saint Barnabas Medical Center

Livingston, New Jersey, 07039, United States

Location

Mercy Medical Center

Rockville Centre, New York, 11570, United States

Location

Atrium Health

Charlotte, North Carolina, 28203, United States

Location

St. David's Healthcare

Austin, Texas, 78705, United States

Location

St. David's North Austin Medical Center

Austin, Texas, 78758, United States

Location

Texas Health

Dallas, Texas, 75231, United States

Location

Hospital Vera Cruz

Belo Horizonte, Minas Gerais, 30140-060, Brazil

Location

CPCLIN - Centro de Pesquisas Clínicas de Natal

Natal, Rio Grande do Norte, 59025-050, Brazil

Location

Hospital São Lucas - PUCRS

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

Location

Sociedade Literaria e Caritativa Santo Agostinho

Criciúma, Santa Catarina, 88811-500, Brazil

Location

Hospital Dia do Pulmão

Blumenau, São Paulo, 89030-101, Brazil

Location

Hospital Guilherme Alvaro

Santos, São Paulo, 11045-904, Brazil

Location

CEMEC - Centro Multidisciplinar de Estudos Clínicos LTDA-EPP

São Bernardo do Campo, São Paulo, 09715-090, Brazil

Location

Clinica de Alergia Martti Antila S/S LTDA

Sorocaba, São Paulo, 18040-425, Brazil

Location

Escola Paulista de Medicina (UNIFESP)

São Paulo, 04037-002, Brazil

Location

Hospital Heliópolis

São Paulo, 04231-030, Brazil

Location

Hospital São Luiz do Jabaquara/IDOR

São Paulo, 04501-000, Brazil

Location

Related Publications (5)

• 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.

  PMID: 35793833 DERIVED

• 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.

  PMID: 34863332 DERIVED

• 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.

  PMID: 33972949 DERIVED

• 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.

  PMID: 33673929 DERIVED

• 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.

  PMID: 33153629 DERIVED

MeSH Terms

Conditions

COVID-19; Pneumonia; Cytokine Release Syndrome

Interventions

lenzilumab; Standard of Care

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Cameron Durrant, MD

  Humanigen, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double-Blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2020
• First Posted: April 17, 2020
• Study Start: May 5, 2020
• Primary Completion: March 1, 2021
• Study Completion: March 1, 2021
• Last Updated: March 3, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will share

Locations

BR (11); US (18)