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

Coronavirus Disease 2019 (COVID-19) Pneumonia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04351152
• Other study ID #: HGEN003-06
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: May 5, 2020
• Est. completion date: March 2021

Study information

• Verified date: March 2021
• Source: Humanigen, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 520
• Est. completion date: March 2021
• Est. primary completion date: March 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Coronavirus Disease 2019 (COVID-19) Pneumonia
• Coronavirus Infections
• Pneumonia

Intervention

Biological:
• Lenzilumab
Administered as an intravenous (IV) infusion

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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Humanigen, Inc.

Countries where clinical trial is conducted

United States,  Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ventilator-free Survival		Up to Day 28
Secondary	Ventilator-free Days		Up to Day 28
Secondary	Duration of Intensive Care Unit (ICU) Stay		Up to Day 28
Secondary	Incidence of Invasive Mechanical Ventilation, ECMO and/or Death		Up to Day 28
Secondary	Time to Death		Up to Day 28
Secondary	All-cause Mortality		Day 28
Secondary	Time to Recovery	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
Secondary	Incidence of severe acute respiratory distress syndrome (ARDS)		Up to Day 28
Secondary	Duration of Hospitalization		Up to Day 28
Secondary	Time to Improvement in 1 or 2 Categories using 8-point Ordinal Scale		Up to Day 28
Secondary	Number of Subjects Alive and Off Oxygen		Up to Day 60
Secondary	Percentage of Participants Experiencing Adverse Events	Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0	Up to Day 60
Secondary	Percentage of Participants Experiencing Serious Adverse Events	Using the NCI CTCAE version 5.0	Up to Day 60
Secondary	Proportion of Subjects Discharged from Hospital		Up to Day 60
Secondary	Time to improvement in oxygenation for > 48 hours		Up to Day 28
Secondary	Incidence of Non-invasive Ventilation (or Use of High-flow Oxygen Device)		Up to Day 28
Secondary	Time to Clinical Improvement, Defined as NEWS2 < 2 Maintained for 24 Hours	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
Secondary	Change from Baseline to Day 28 in Clinical status Based on the 8-point Ordinal Scale		Up to Day 28
Secondary	Duration of Time on Low-flow or High-flow Supplemental Oxygen		Up to Day 28