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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

Tracking Information
First Submitted Date  ICMJE May 24, 2021
First Posted Date  ICMJE May 25, 2021
Last Update Posted Date August 10, 2021
Estimated Study Start Date  ICMJE August 9, 2021
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 3, 2021)
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
Original Primary Outcome Measures  ICMJE
 (submitted: May 24, 2021)
Time to recovery [ Time Frame: 28 days ]
Time to recovery, with the day of recovery defined as the first day, during the 28 days after enrollment, on which a patient attained category 1, 2, or 3 on the eight-category ordinal scale, 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
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 3, 2021)
  • Proportion of patients clinically recovered [ Time Frame: At days 14, 28, 42, and 60 ]
    Ordinal Scale of 1, 2 or 3
  • All-cause mortality [ Time Frame: At days 14, 28, 42, and 60 ]
    All-cause mortality
  • Proportion of patients discharged alive [ Time Frame: At days 14, 28, 42, and 60 ]
    Ordinal Scale 1 or 2
  • Clinical Status [ Time Frame: Days 14, 28, 42, and 60 ]
    Ordinal Scale
  • Duration of invasive mechanical ventilation or ECMO [ Time Frame: 28 days ]
    Days
  • Length of hospital stay [ Time Frame: 28 days ]
    Days
  • Length of ICU stay [ Time Frame: 28 days ]
    Days
Original Secondary Outcome Measures  ICMJE
 (submitted: May 24, 2021)
  • Clinical Recovery [ Time Frame: Days 14, 28, 42, and 60 ]
    Ordinal Scales of 1, 2 or 3
  • All-cause mortality [ Time Frame: Days 14, 28, 42, and 60 ]
    All-cause mortality
  • Proportion of patients discharged alive [ Time Frame: Days 14, 28, 42, and 60 ]
    Ordinal Scales 1 or 2
  • Clinical Status [ Time Frame: Days 14, 28, 42, and 60 ]
    Ordinal Scale
  • Duration of invasive mechanical ventilation or ECMO [ Time Frame: 28 days ]
    Days
  • Length of hospital stay [ Time Frame: 28 days ]
    Days
  • Length of ICU stay [ Time Frame: 28 days ]
    Days
  • Change from baseline in serum cytokine levels [ Time Frame: Days 7 and 14 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Leronlimab in Patients With Coronavirus Disease 2019 (COVID-19) With Need for Mechanical Ventilation or Extracorporeal Membrane Oxygenation
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 Patients With Coronavirus Disease 2019 (COVID-19) With Need for Mechanical Ventilation or Extracorporeal Membrane Oxygenation
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.

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
  • Drug: Placebo
    Placebo
Study Arms  ICMJE
  • Experimental: Leronlimab (700 mg)
    Leronlimab 700 mg intravenously once a week (up to 4 doses) until hospital discharge
    Intervention: Drug: Leronlimab
  • Placebo Comparator: Placebo
    Placebo intravenously 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 Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: August 3, 2021)
316
Original Estimated Enrollment  ICMJE
 (submitted: May 24, 2021)
306
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
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: Otavio Berwanger, MD, PhD +551121515915 otavio.berwanger@einstein.br
Contact: Patricia Guimaraes, MD, PhD +551121515915 patricia.oguimaraes@einstein.br
Listed Location Countries  ICMJE Brazil
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04901689
Other Study ID Numbers  ICMJE ARO_21_018_002
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
Responsible Party Hospital Israelita Albert Einstein
Study Sponsor  ICMJE Hospital Israelita Albert Einstein
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