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Leronlimab in Moderately Ill Patients With COVID-19 Pneumonia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04901676
Recruitment Status : Suspended (Pending DSMB evaluation)
First Posted : May 25, 2021
Last Update Posted : April 15, 2022
Sponsor:
Collaborator:
CytoDyn, Inc.
Information provided by (Responsible Party):
Hospital Israelita Albert Einstein

Tracking Information
First Submitted Date  ICMJE May 24, 2021
First Posted Date  ICMJE May 25, 2021
Last Update Posted Date April 15, 2022
Actual Study Start Date  ICMJE September 9, 2021
Estimated Primary Completion Date January 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 3, 2021)
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
Original Primary Outcome Measures  ICMJE
 (submitted: May 24, 2021)
Death or respiratory failure until day 28 [ Time Frame: 28 days ]
Categories 6, 7, or 8 on the eight-category ordinal scale
  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
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 3, 2021)
  • Time to clinical recovery [ Time Frame: 28 days ]
    Categories 1, 2 and 3 on a 8-point ordinal scale
  • Death or intubation until day 28 [ Time Frame: 28 days ]
    Categories 7 or 8 on the eight-point ordinal scale
  • Proportion of patients clinically recovered [ Time Frame: Days 14, 28, 42, and 60 ]
    Categories 1, 2 and 3 on a 8-point ordinal scale
  • All-cause mortality [ Time Frame: Days 14, 28, 42, and 60 ]
  • Proportion of patients discharged alive [ Time Frame: Days 14, 28, 42, and 60 ]
    Categories 1 and 2 on a 8-point ordinal scale
  • Clinical status [ Time Frame: Days 14, 28, 42, and 60 ]
    On a 8 point ordinal scale
  • Length of hospital stay [ Time Frame: 28 days ]
    days
Original Secondary Outcome Measures  ICMJE
 (submitted: May 24, 2021)
  • Time to clinical recovery [ Time Frame: 28 days ]
    Categories 1, 2 and 3 on a 8-point ordinal scale
  • Death or intubation until day 28 [ Time Frame: 28 days ]
    Categories 7 or 8 on the eight-point ordinal scale
  • Clinical recovery [ Time Frame: Days 14, 28, 42, and 60 ]
    Categories 1, 2 and 3 on a 8-point ordinal scale
  • All-cause mortality [ Time Frame: Days 14, 28, 42, and 60 ]
  • Proportion of patients discharged alive [ Time Frame: Days 14, 28, 42, and 60 ]
    Categories 1 and 2 on a 8-point ordinal scale
  • Clinical status [ Time Frame: Days 14, 28, 42, and 60 ]
    On a 8 point ordinal scale
  • Length of hospital stay [ Time Frame: 28 days ]
    days
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Leronlimab in Moderately Ill Patients With COVID-19 Pneumonia
Official Title  ICMJE 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
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).

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE COVID-19 Pneumonia
Intervention  ICMJE
  • Drug: Leronlimab
    Leronlimab 700 mg (first dose) followed by weekly 350 mg
  • Drug: Placebo
    Placebo
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Leronlimab
  • Placebo Comparator: Placebo
    Placebo subcutaneously once a week (up to 4 doses) until hospital discharge
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Suspended
Estimated Enrollment  ICMJE
 (submitted: August 3, 2021)
612
Original Estimated Enrollment  ICMJE
 (submitted: May 24, 2021)
594
Estimated Study Completion Date  ICMJE February 2023
Estimated Primary Completion Date January 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04901676
Other Study ID Numbers  ICMJE ARO_21_018_001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Hospital Israelita Albert Einstein
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Hospital Israelita Albert Einstein
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE CytoDyn, Inc.
Investigators  ICMJE Not Provided
PRS Account Hospital Israelita Albert Einstein
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP