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

NCT04901689 | Suspended Phase 3 DMC FDA Drug

• 1 other identifier: ARO_21_018_002
• Study Type: interventional
• Target: 316
• Locations: 1 country
• Sites: 23

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).

Conditions

COVID-19 Pneumonia

Keywords

COVID-19; Pneumonia; Leronlimab

Outcome Measures

Primary Outcomes (1)

• 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: 1. Not hospitalized, no limitations on activities 2. Not hospitalized, limitation on activities and/or requiring home oxygen 3. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care 4. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) 5. Hospitalized, requiring supplemental oxygen 6. Hospitalized, on non-invasive ventilation or high flow oxygen devices 7. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) 8. Death

  28 days

Secondary Outcomes (7)

• Proportion of patients clinically recovered

  At days 14, 28, 42, and 60

• All-cause mortality

  At days 14, 28, 42, and 60

• Proportion of patients discharged alive

  At days 14, 28, 42, and 60

• Clinical Status

  Days 14, 28, 42, and 60

• Duration of invasive mechanical ventilation or ECMO

  28 days

Study Arms (2)

Leronlimab (700 mg)

EXPERIMENTAL

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

Drug: Leronlimab

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Leronlimab DRUG

Leronlimab 700 mg

Leronlimab (700 mg)

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

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

You may qualify if:

• Male or females aged ≥ 18 years
• 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.
• Evidence of pneumonia (pulmonary infiltrates) at chest radiography or computed tomography compatible with COVID-19.
• Laboratory-confirmed novel coronavirus (SARS-CoV-2) infection as determined by polymerase chain reaction (PCR).
• Subject (or legally authorized representative) provides written or oral informed consent prior to initiation of any study procedures.
• 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.

You may not qualify if:

• Subjects who had been on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) for \>72 hours prior to the screening.
• Subjects who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to leronlimab (PRO 140) are not eligible.
• Inability to provide informed consent (from subject or legally authorized representative) or to comply with test requirements.
• 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.
• Pregnancy or breast feeding.
• Subject participating in another study with for an investigational treatment.
• 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.
• Participants who are immunocompromised, with known immunodeficiencies, or taking potent immunosuppressive agents (e.g., azathioprine, cyclosporine).

Sponsors & Collaborators

• Hospital Israelita Albert Einstein: lead
• CytoDyn, Inc.: collaborator

Study Sites (23)

Hospital Dr Jayme dos Santos Neves

Laranjeiras, Espírito Santo, Brazil

Location

Clinica São Roque

Ipiaú, Estado de Bahia, Brazil

Location

Santa Casa de Misericórdia da Bahia - Hospital Santa Izabel

Salvador, Estado de Bahia, Brazil

Location

Hospital do Coração do Brasil

Brasília, Federal District, Brazil

Location

Santa Casa de Misericórdia de Passos

Passos, Minas Gerais, Brazil

Location

Hospital 9 de Julho

São Paulo, Please Select, Brazil

Location

Hospital São Lucas Copacabana

Rio de Janeiro, Rio de Janeiro, Brazil

Location

Instituto Atena de Pesquisa Clínica

Natal, Rio Grande do Norte, Brazil

Location

Hospital São Vicente de Paulo

Passo Fundo, Rio Grande do Sul, Brazil

Location

Hospital Mãe de Deus

Porto Alegre, Rio Grande do Sul, Brazil

Location

Irmandade da Santa Casa de Misericórdia Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Location

Centro de Pesquisa Clínica do Coração

Aracaju, Sergipe, Brazil

Location

Fundação PIO XII

Barretos, São Paulo, Brazil

Location

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

Bragança Paulista, São Paulo, Brazil

Location

Instituto de Pesquisa Clínica de Campinas

Campinas, São Paulo, Brazil

Location

Hospital Santa Ignes

Indaiatuba, São Paulo, Brazil

Location

Fundação Faculdade Regional de Medicina de São José do Rio Preto

São José do Rio Preto, São Paulo, Brazil

Location

BP Mirante

São Paulo, São Paulo, Brazil

Location

Hospital Alemão Oswaldo Cruz

São Paulo, São Paulo, Brazil

Location

Hospital Beneficência Portuguesa

São Paulo, São Paulo, Brazil

Location

Santa Casa de Votuporanga

Votuporanga, São Paulo, Brazil

Location

Hospital Israelita Albert Einstein

São Paulo, Brazil

Location

Hospital M'Boi Mirim

São Paulo, Brazil

Location

MeSH Terms

Conditions

COVID-19; Pneumonia

Interventions

leronlimab

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2021
• First Posted: May 25, 2021
• Study Start: October 23, 2021
• Primary Completion: February 1, 2023
• Study Completion: February 1, 2023
• Last Updated: April 15, 2022

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

BR (23)