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

Primary Purpose

COVID-19 Pneumonia

Status
Suspended
Phase
Phase 3
Locations
Brazil
Study Type
Interventional
Intervention
Leronlimab
Placebo
Sponsored by
Hospital Israelita Albert Einstein
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID-19 Pneumonia focused on measuring COVID-19, Pneumonia, Leronlimab

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Clinica São Roque
  • Santa Casa de Misericórdia da Bahia - Hospital Santa Izabel
  • Hospital do Coração do Brasil
  • Hospital Dr Jayme dos Santos Neves
  • Santa Casa de Misericórdia de Passos
  • Hospital 9 de Julho
  • Hospital São Lucas Copacabana
  • Instituto Atena de Pesquisa Clínica
  • Hospital São Vicente de Paulo
  • Hospital Mãe de Deus
  • Irmandade da Santa Casa de Misericórdia Porto Alegre
  • Centro de Pesquisa Clínica do Coração
  • Fundação PIO XII
  • Irmandade do Sr. Bom Jesus dos Passos da Santa Casa de Misericórdia de Bragança Paulista
  • Instituto de Pesquisa Clínica de Campinas
  • Hospital Santa Ignes
  • Hospital Alemão Oswaldo Cruz
  • Hospital Beneficência Portuguesa
  • Fundação Faculdade Regional de Medicina de São José do Rio Preto
  • BP Mirante
  • Santa Casa de Votuporanga
  • Hospital Israelita Albert Einstein
  • Hospital M'Boi Mirim

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Leronlimab (700 mg)

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Proportion of patients clinically recovered
Ordinal Scale of 1, 2 or 3
All-cause mortality
All-cause mortality
Proportion of patients discharged alive
Ordinal Scale 1 or 2
Clinical Status
Ordinal Scale
Duration of invasive mechanical ventilation or ECMO
Days
Length of hospital stay
Days
Length of ICU stay
Days

Full Information

First Posted
May 24, 2021
Last Updated
April 8, 2022
Sponsor
Hospital Israelita Albert Einstein
Collaborators
CytoDyn, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04901689
Brief Title
Leronlimab in Patients With Coronavirus Disease 2019 (COVID-19) With Need for Mechanical Ventilation or Extracorporeal Membrane Oxygenation
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Suspended
Why Stopped
Pending DSMB evaluation
Study Start Date
October 23, 2021 (Actual)
Primary Completion Date
February 2023 (Anticipated)
Study Completion Date
February 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospital Israelita Albert Einstein
Collaborators
CytoDyn, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19 Pneumonia
Keywords
COVID-19, Pneumonia, Leronlimab

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
316 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Leronlimab (700 mg)
Arm Type
Experimental
Arm Description
Leronlimab 700 mg intravenously once a week (up to 4 doses) until hospital discharge
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo intravenously once a week (up to 4 doses) until hospital discharge
Intervention Type
Drug
Intervention Name(s)
Leronlimab
Intervention Description
Leronlimab 700 mg
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Cumulative proportion of clinical recovery
Description
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: Not hospitalized, no limitations on activities Not hospitalized, limitation on activities and/or requiring home oxygen Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, requiring supplemental oxygen Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Death
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Proportion of patients clinically recovered
Description
Ordinal Scale of 1, 2 or 3
Time Frame
At days 14, 28, 42, and 60
Title
All-cause mortality
Description
All-cause mortality
Time Frame
At days 14, 28, 42, and 60
Title
Proportion of patients discharged alive
Description
Ordinal Scale 1 or 2
Time Frame
At days 14, 28, 42, and 60
Title
Clinical Status
Description
Ordinal Scale
Time Frame
Days 14, 28, 42, and 60
Title
Duration of invasive mechanical ventilation or ECMO
Description
Days
Time Frame
28 days
Title
Length of hospital stay
Description
Days
Time Frame
28 days
Title
Length of ICU stay
Description
Days
Time Frame
28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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). Patients with estimated discharge or transfer for other hospital in the first 72 hours of study inclusion. Patients with low probability of survival in the first 48 hours of study inclusion.
Facility Information:
Facility Name
Clinica São Roque
City
Ipiaú
State/Province
BA
Country
Brazil
Facility Name
Santa Casa de Misericórdia da Bahia - Hospital Santa Izabel
City
Salvador
State/Province
BA
Country
Brazil
Facility Name
Hospital do Coração do Brasil
City
Brasilia
State/Province
DF
Country
Brazil
Facility Name
Hospital Dr Jayme dos Santos Neves
City
Laranjeiras
State/Province
ES
Country
Brazil
Facility Name
Santa Casa de Misericórdia de Passos
City
Passos
State/Province
MG
Country
Brazil
Facility Name
Hospital 9 de Julho
City
Sao Paulo
State/Province
Please Select
Country
Brazil
Facility Name
Hospital São Lucas Copacabana
City
Rio De Janeiro
State/Province
RJ
Country
Brazil
Facility Name
Instituto Atena de Pesquisa Clínica
City
Natal
State/Province
RN
Country
Brazil
Facility Name
Hospital São Vicente de Paulo
City
Passo Fundo
State/Province
RS
Country
Brazil
Facility Name
Hospital Mãe de Deus
City
Porto Alegre
State/Province
RS
Country
Brazil
Facility Name
Irmandade da Santa Casa de Misericórdia Porto Alegre
City
Porto Alegre
State/Province
RS
Country
Brazil
Facility Name
Centro de Pesquisa Clínica do Coração
City
Aracaju
State/Province
SE
Country
Brazil
Facility Name
Fundação PIO XII
City
Barretos
State/Province
SP
Country
Brazil
Facility Name
Irmandade do Sr. Bom Jesus dos Passos da Santa Casa de Misericórdia de Bragança Paulista
City
Bragança Paulista
State/Province
SP
Country
Brazil
Facility Name
Instituto de Pesquisa Clínica de Campinas
City
Campinas
State/Province
SP
Country
Brazil
Facility Name
Hospital Santa Ignes
City
Indaiatuba
State/Province
SP
Country
Brazil
Facility Name
Hospital Alemão Oswaldo Cruz
City
Sao Paulo
State/Province
SP
Country
Brazil
Facility Name
Hospital Beneficência Portuguesa
City
Sao Paulo
State/Province
SP
Country
Brazil
Facility Name
Fundação Faculdade Regional de Medicina de São José do Rio Preto
City
São José Do Rio Preto
State/Province
SP
Country
Brazil
Facility Name
BP Mirante
City
São Paulo
State/Province
SP
Country
Brazil
Facility Name
Santa Casa de Votuporanga
City
Votuporanga
State/Province
SP
Country
Brazil
Facility Name
Hospital Israelita Albert Einstein
City
Sao Paulo
Country
Brazil
Facility Name
Hospital M'Boi Mirim
City
São Paulo
Country
Brazil

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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