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

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ClinicalTrials.gov Identifier: NCT04901689
Recruitment Status : Not yet recruiting
First Posted : May 25, 2021
Last Update Posted : August 10, 2021
Sponsor:
Collaborator:
CytoDyn, Inc.
Information provided by (Responsible Party):
Hospital Israelita Albert Einstein

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).


Condition or disease Intervention/treatment Phase
COVID-19 Pneumonia Drug: Leronlimab Drug: Placebo Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 316 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Estimated Study Start Date : August 9, 2021
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Leronlimab (700 mg)
Leronlimab 700 mg intravenously once a week (up to 4 doses) until hospital discharge
Drug: Leronlimab
Leronlimab 700 mg

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




Primary Outcome Measures :
  1. Cumulative proportion of clinical recovery [ Time Frame: 28 days ]

    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


Secondary Outcome Measures :
  1. Proportion of patients clinically recovered [ Time Frame: At days 14, 28, 42, and 60 ]
    Ordinal Scale of 1, 2 or 3

  2. All-cause mortality [ Time Frame: At days 14, 28, 42, and 60 ]
    All-cause mortality

  3. Proportion of patients discharged alive [ Time Frame: At days 14, 28, 42, and 60 ]
    Ordinal Scale 1 or 2

  4. Clinical Status [ Time Frame: Days 14, 28, 42, and 60 ]
    Ordinal Scale

  5. Duration of invasive mechanical ventilation or ECMO [ Time Frame: 28 days ]
    Days

  6. Length of hospital stay [ Time Frame: 28 days ]
    Days

  7. Length of ICU stay [ Time Frame: 28 days ]
    Days



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04901689


Contacts
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Contact: Otavio Berwanger, MD, PhD +551121515915 otavio.berwanger@einstein.br
Contact: Patricia Guimaraes, MD, PhD +551121515915 patricia.oguimaraes@einstein.br

Locations
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Brazil
Hospital Israelita Albert Einstein
Sao Paulo, Brazil
Contact: Remo Furtado, MD, PhD         
Sponsors and Collaborators
Hospital Israelita Albert Einstein
CytoDyn, Inc.
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Responsible Party: Hospital Israelita Albert Einstein
ClinicalTrials.gov Identifier: NCT04901689    
Other Study ID Numbers: ARO_21_018_002
First Posted: May 25, 2021    Key Record Dates
Last Update Posted: August 10, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hospital Israelita Albert Einstein:
COVID-19
Pneumonia
Leronlimab
Additional relevant MeSH terms:
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Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections