Leronlimab in Patients With Coronavirus Disease 2019 (COVID-19) With Need for Mechanical Ventilation or Extracorporeal Membrane Oxygenation

COVID-19 Pneumonia Clinical Trial

Official title:

A Phase 3, Randomized, Double Blind, Placebo Controlled Trial to Evaluate the Efficacy and Safety of Leronlimab in Combination With Standard of Care for Patients With Coronavirus Disease 2019 (COVID-19) With Need for Mechanical Ventilation or Extracorporeal Membrane Oxygenation

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT04901689
• Other study ID #: ARO_21_018_002
• Status: Suspended
• Phase: Phase 3
• Start date: October 23, 2021
• Est. completion date: February 2023

Study information

• Verified date: May 2021
• Source: Hospital Israelita Albert Einstein
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Leronlimab (PRO 140) is a humanized IgG4,k monoclonal antibody (mAb) that recognizes the C-C chemokine receptor type 5 (CCR5). Disruption of the C-C chemokine ligand 5 (CCL5)-CCR5 axis via leronlimab-mediated CCR5 blockade might prevent pulmonary trafficking of pro-inflammatory leukocytes and dampen pathogenic immune activation in coronavirus disease 2019 (COVID-19).

The purpose of the study is to assess the safety and efficacy of leronlimab plus standard of care in critically ill patients hospitalized with COVID-19 pneumonia who are requiring mechanical ventilation or extracorporeal oxigenation (ECMO).

Description:

Leronlimab (PRO 140) is a humanized IgG4,k monoclonal antibody (mAb) that recognizes the C-C chemokine receptor type 5 (CCR5). CCR5 is expressed predominantly on T cells but also found on macrophages, dendritic cells, and eosinophils to mediate chemotaxis in response to its cognate ligands that include CCL5 (RANTES), CCL3 (MIP-1α), and CCL4 (MIP-1β). These ligands are integral in the recruitment of these immune cells to inflammatory sites. The immunopathogenesis of COVID-19 likely involves the excessive influx of immune cells into the lung. Disruption of the CCL5-CCR5 axis via leronlimab-mediated CCR5 blockade might prevent pulmonary trafficking of pro-inflammatory leukocytes and dampen pathogenic immune activation in COVID-19.

The purpose of the study is to assess the safety and efficacy of leronlimab plus standard of care in critically ill patients hospitalized with COVID-19 pneumonia who are requiring mechanical ventilation or extracorporeal oxigenation (ECMO).

This is a Phase 3, 2-arm, randomized, double blind, placebo controlled, multicenter study to evaluate the safety and efficacy of leronlimab (PRO 140) as an add on therapy to the institutional standard of care (SoC) for the management of critically ill patients with COVID-19 pneumonia.

Patients will be randomized in a 1:1 ratio to receive up to four doses of 700 mg leronlimab (PRO 140) or placebo. Leronlimab or placebo will be administered by 30-minute intravenous (IV) infusion weekly over a 4-week treatment period. No treatments will be administered post-discharge.

The participant will be evaluated on each study day while hospitalized up until and including Day 28. The daily visits will capture clinical status - ordinal scale and the occurrence of adverse events. A complete follow-up assessment will be performed at Days 7, 14, 21, 28, 42 and 60 for those who are hospitalized at these specific timepoints. Follow-up visits can be conducted as telephone or video contact visits, if subject is discharged from the hospital prior to the complete follow-up visits.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 316
• Est. completion date: February 2023
• Est. primary completion date: February 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male or females aged = 18 years

2. Critically ill patients with COVID-19 (defined as Ordinal Scale score of 7):

Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) for less than 72 hours.

3. Evidence of pneumonia (pulmonary infiltrates) at chest radiography or computed tomography compatible with COVID-19.

4. Laboratory-confirmed novel coronavirus (SARS-CoV-2) infection as determined by polymerase chain reaction (PCR).

5. Subject (or legally authorized representative) provides written or oral informed consent prior to initiation of any study procedures.

6. Women of childbearing potential and their partner must agree to use at least one highly effective method of contraception (e.g., hormonal contraceptives [implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings], intrauterine devices, bilateral tubal occlusion, or sexual abstinence) for the duration of the study.

Exclusion Criteria:

1. Subjects who had been on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) for >72 hours prior to the screening.

2. Subjects who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to leronlimab (PRO 140) are not eligible.

3. Inability to provide informed consent (from subject or legally authorized representative) or to comply with test requirements.

4. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk associated with study participation or, in the investigator's judgment, make the participant inappropriate for the study.

5. Pregnancy or breast feeding.

6. Subject participating in another study with for an investigational treatment.

7. Suspected or known active systemic bacterial, fungal, or viral infections (with the exception of COVID-19), that may increase the risk for the study participant based on investigator judgement.

8. Participants who are immunocompromised, with known immunodeficiencies, or taking potent immunosuppressive agents (e.g., azathioprine, cyclosporine).

9. Patients with estimated discharge or transfer for other hospital in the first 72 hours of study inclusion.

10. Patients with low probability of survival in the first 48 hours of study inclusion.

Related Conditions & MeSH terms

• COVID-19
• COVID-19 Pneumonia
• Pneumonia

Intervention

Drug:
• Leronlimab
Leronlimab 700 mg
• Placebo
Placebo

Locations

Country	Name	City	State
Brazil	Centro de Pesquisa Clínica do Coração	Aracaju	SE
Brazil	Fundação PIO XII	Barretos	SP
Brazil	Irmandade do Sr. Bom Jesus dos Passos da Santa Casa de Misericórdia de Bragança Paulista	Bragança Paulista	SP
Brazil	Hospital do Coração do Brasil	Brasilia	DF
Brazil	Instituto de Pesquisa Clínica de Campinas	Campinas	SP
Brazil	Hospital Santa Ignes	Indaiatuba	SP
Brazil	Clinica São Roque	Ipiaú	BA
Brazil	Hospital Dr Jayme dos Santos Neves	Laranjeiras	ES
Brazil	Instituto Atena de Pesquisa Clínica	Natal	RN
Brazil	Hospital São Vicente de Paulo	Passo Fundo	RS
Brazil	Santa Casa de Misericórdia de Passos	Passos	MG
Brazil	Hospital Mãe de Deus	Porto Alegre	RS
Brazil	Irmandade da Santa Casa de Misericórdia Porto Alegre	Porto Alegre	RS
Brazil	Hospital São Lucas Copacabana	Rio De Janeiro	RJ
Brazil	Santa Casa de Misericórdia da Bahia - Hospital Santa Izabel	Salvador	BA
Brazil	Fundação Faculdade Regional de Medicina de São José do Rio Preto	São José Do Rio Preto	SP
Brazil	Hospital 9 de Julho	Sao Paulo	Please Select
Brazil	Hospital Alemão Oswaldo Cruz	Sao Paulo	SP
Brazil	Hospital Beneficência Portuguesa	Sao Paulo	SP
Brazil	Hospital Israelita Albert Einstein	Sao Paulo
Brazil	BP Mirante	São Paulo	SP
Brazil	Hospital M'Boi Mirim	São Paulo
Brazil	Santa Casa de Votuporanga	Votuporanga	SP

Sponsors (2)

Lead Sponsor	Collaborator
Hospital Israelita Albert Einstein	CytoDyn, Inc.

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cumulative proportion of clinical recovery	Patients will be considered to have recovered if they attain categories 1, 2, or 3 on the eight-category ordinal scale within 28 days, as follows: Not hospitalized, no limitations on activities; Not hospitalized, limitation on activities and/or requiring home oxygen; Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Death	28 days
Secondary	Proportion of patients clinically recovered	Ordinal Scale of 1, 2 or 3	At days 14, 28, 42, and 60
Secondary	All-cause mortality	All-cause mortality	At days 14, 28, 42, and 60
Secondary	Proportion of patients discharged alive	Ordinal Scale 1 or 2	At days 14, 28, 42, and 60
Secondary	Clinical Status	Ordinal Scale	Days 14, 28, 42, and 60
Secondary	Duration of invasive mechanical ventilation or ECMO	Days	28 days
Secondary	Length of hospital stay	Days	28 days
Secondary	Length of ICU stay	Days	28 days