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

NCT ID: NCT04901689

Last Updated: 2022-04-15

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: PHASE3
• Total Enrollment: 316 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-23
• Study Completion Date: 2023-02-28

Brief 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).

Detailed 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.

Conditions

COVID-19 Pneumonia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Leronlimab (700 mg)

Leronlimab 700 mg intravenously once a week (up to 4 doses) until hospital discharge

Group Type: EXPERIMENTAL

Leronlimab

Intervention Type: DRUG

Leronlimab 700 mg

Placebo

Placebo intravenously once a week (up to 4 doses) until hospital discharge

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

Leronlimab

Leronlimab 700 mg

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CytoDyn, Inc.

INDUSTRY

Sponsor Role: collaborator

Hospital Israelita Albert Einstein

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hospital Dr Jayme dos Santos Neves

Laranjeiras, Espírito Santo, Brazil

Clinica São Roque

Ipiaú, Estado de Bahia, Brazil

Santa Casa de Misericórdia da Bahia - Hospital Santa Izabel

Salvador, Estado de Bahia, Brazil

Hospital do Coração do Brasil

Brasília, Federal District, Brazil

Santa Casa de Misericórdia de Passos

Passos, Minas Gerais, Brazil

Hospital 9 de Julho

São Paulo, Please Select, Brazil

Hospital São Lucas Copacabana

Rio de Janeiro, Rio de Janeiro, Brazil

Instituto Atena de Pesquisa Clínica

Natal, Rio Grande do Norte, Brazil

Hospital São Vicente de Paulo

Passo Fundo, Rio Grande do Sul, Brazil

Hospital Mãe de Deus

Porto Alegre, Rio Grande do Sul, Brazil

Irmandade da Santa Casa de Misericórdia Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Centro de Pesquisa Clínica do Coração

Aracaju, Sergipe, Brazil

Fundação PIO XII

Barretos, São Paulo, Brazil

Irmandade do Sr. Bom Jesus dos Passos da Santa Casa de Misericórdia de Bragança Paulista

Bragança Paulista, São Paulo, Brazil

Instituto de Pesquisa Clínica de Campinas

Campinas, São Paulo, Brazil

Hospital Santa Ignes

Indaiatuba, São Paulo, Brazil

Fundação Faculdade Regional de Medicina de São José do Rio Preto

São José do Rio Preto, São Paulo, Brazil

BP Mirante

São Paulo, São Paulo, Brazil

Hospital Alemão Oswaldo Cruz

São Paulo, São Paulo, Brazil

Hospital Beneficência Portuguesa

São Paulo, São Paulo, Brazil

Santa Casa de Votuporanga

Votuporanga, São Paulo, Brazil

Hospital Israelita Albert Einstein

São Paulo, , Brazil

Hospital M'Boi Mirim

São Paulo, , Brazil

Countries

Brazil

Other Identifiers

ARO_21_018_002

Identifier Type: -

Identifier Source: org_study_id