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Leronlimab in Moderately Ill Patients With COVID-19 Pneumonia

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ClinicalTrials.gov Identifier: NCT04901676
Recruitment Status : Recruiting
First Posted : May 25, 2021
Last Update Posted : September 16, 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 patients hospitalized with COVID-19 pneumonia who are not requiring mechanical ventilation or extracorporeal oxygenation (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 patients hospitalized with COVID-19 pneumonia who are not requiring mechanical ventilation or extracorporeal oxygenation (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 moderately ill patients with COVID-19 pneumonia.

Patients will be randomized in a 1:1 ratio to receive up to four doses of leronlimab (PRO 140) or placebo. Leronlimab (700 mg followed by 350 mg weekly) or placebo will be administered subcutaneously 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 : 612 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 Moderately Ill Patients With Coronavirus Disease 2019 (COVID-19) Pneumonia
Actual Study Start Date : September 9, 2021
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : February 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pneumonia

Arm Intervention/treatment
Experimental: Leronlimab
Leronlimab subcutaneously once a week (up to 4 doses) until hospital discharge. The first dose will be of 700 mg, followed by weekly doses of 350 mg.
Drug: Leronlimab
Leronlimab 700 mg (first dose) followed by weekly 350 mg

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




Primary Outcome Measures :
  1. Cumulative incidence of death or respiratory failure until day 28 [ Time Frame: 28 days ]

    Rates of participants who attain categories 6, 7, or 8 on the eight-category ordinal scale within 28 days

    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. Time to clinical recovery [ Time Frame: 28 days ]
    Categories 1, 2 and 3 on a 8-point ordinal scale

  2. Death or intubation until day 28 [ Time Frame: 28 days ]
    Categories 7 or 8 on the eight-point ordinal scale

  3. Proportion of patients clinically recovered [ Time Frame: Days 14, 28, 42, and 60 ]
    Categories 1, 2 and 3 on a 8-point ordinal scale

  4. All-cause mortality [ Time Frame: Days 14, 28, 42, and 60 ]
  5. Proportion of patients discharged alive [ Time Frame: Days 14, 28, 42, and 60 ]
    Categories 1 and 2 on a 8-point ordinal scale

  6. Clinical status [ Time Frame: Days 14, 28, 42, and 60 ]
    On a 8 point ordinal scale

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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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. Moderately ill patients with COVID-19 (defined as Ordinal Scale of 5 or 6): Hospitalized, requiring supplemental oxygen or hospitalized, on non-invasive ventilation or high flow oxygen devices
  3. Evidence of pneumonia (pulmonary infiltrates) at chest radiography or computed tomography compatible with COVID-19.
  4. Hospitalization for less than 72 hours, receiving standard of care treatment for COVID-19.
  5. Laboratory-confirmed novel coronavirus (SARS-CoV-2) infection as determined by polymerase chain reaction (PCR).
  6. Subject (or legally authorized representative) provides written or oral informed consent prior to initiation of any study procedures.
  7. 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 on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO).
  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): NCT04901676


Contacts
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Contact: Otavio Berwanger, MD, PhD +551121515915 ext 53945 otavio.berwanger@einstein.br
Contact: Patricia Guimaraes, MD, PhD +551121515915 ext 53945 patricia.oguimaraes@einstein.br

Locations
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Sponsors and Collaborators
Hospital Israelita Albert Einstein
CytoDyn, Inc.
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Responsible Party: Hospital Israelita Albert Einstein
ClinicalTrials.gov Identifier: NCT04901676    
Other Study ID Numbers: ARO_21_018_001
First Posted: May 25, 2021    Key Record Dates
Last Update Posted: September 16, 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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COVID-19
Pneumonia
Respiratory Tract Infections
Infections
Pneumonia, Viral
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Leronlimab
HIV Fusion Inhibitors
Viral Fusion Protein Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents