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Leronlimab in Moderately Ill Patients With COVID-19 Pneumonia

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. 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.

Sites / Locations

  • Clinica São Roque
  • Instituto de Ensino e Pesquisa do Hospital da Bahia
  • Santa Casa de Misericórdia da Bahia - Hospital Santa Izabel
  • Hospital do Coração do Brasil
  • Hospital Vitoria
  • Hospital Felicio Rocho
  • Santa Casa de Passos
  • 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
  • Santa Casa de Santos
  • BP Mirante
  • Fundação Faculdade Regional de Medicina de São José do Rio Preto
  • Associação Beneficente Síria - Hospital do Coração (HCor)
  • Hospital 9 de Julho
  • Hospital Alemão Oswaldo Cruz
  • Hospital Beneficência Portuguesa
  • Hospital M'Boi Mirim
  • Hospital Santa Paula
  • Santa Casa de Votuporanga
  • Hospital Israelita Albert Einstein

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Leronlimab

Placebo

Arm Description

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.

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

Outcomes

Primary Outcome Measures

Cumulative incidence of death or respiratory failure until day 28
Rates of participants who attain categories 6, 7, or 8 on the eight-category ordinal scale within 28 days 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

Time to clinical recovery
Categories 1, 2 and 3 on a 8-point ordinal scale
Death or intubation until day 28
Categories 7 or 8 on the eight-point ordinal scale
Proportion of patients clinically recovered
Categories 1, 2 and 3 on a 8-point ordinal scale
All-cause mortality
Proportion of patients discharged alive
Categories 1 and 2 on a 8-point ordinal scale
Clinical status
On a 8 point ordinal scale
Length of hospital 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
NCT04901676
Brief Title
Leronlimab in Moderately Ill Patients With COVID-19 Pneumonia
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Suspended
Why Stopped
Pending DSMB evaluation
Study Start Date
September 9, 2021 (Actual)
Primary Completion Date
January 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 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.

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
612 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Leronlimab
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo subcutaneously once a week (up to 4 doses) until hospital discharge
Intervention Type
Drug
Intervention Name(s)
Leronlimab
Intervention Description
Leronlimab 700 mg (first dose) followed by weekly 350 mg
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Cumulative incidence of death or respiratory failure until day 28
Description
Rates of participants who attain categories 6, 7, or 8 on the eight-category ordinal scale within 28 days 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
Time to clinical recovery
Description
Categories 1, 2 and 3 on a 8-point ordinal scale
Time Frame
28 days
Title
Death or intubation until day 28
Description
Categories 7 or 8 on the eight-point ordinal scale
Time Frame
28 days
Title
Proportion of patients clinically recovered
Description
Categories 1, 2 and 3 on a 8-point ordinal scale
Time Frame
Days 14, 28, 42, and 60
Title
All-cause mortality
Time Frame
Days 14, 28, 42, and 60
Title
Proportion of patients discharged alive
Description
Categories 1 and 2 on a 8-point ordinal scale
Time Frame
Days 14, 28, 42, and 60
Title
Clinical status
Description
On a 8 point ordinal scale
Time Frame
Days 14, 28, 42, and 60
Title
Length of hospital 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 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 Evidence of pneumonia (pulmonary infiltrates) at chest radiography or computed tomography compatible with COVID-19. Hospitalization for less than 72 hours, receiving standard of care treatment for 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 on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO). 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
Instituto de Ensino e Pesquisa do Hospital da Bahia
City
Salvador
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
Brasília
State/Province
DF
Country
Brazil
Facility Name
Hospital Vitoria
City
Vitória
State/Province
ES
Country
Brazil
Facility Name
Hospital Felicio Rocho
City
Belo Horizonte
State/Province
MG
Country
Brazil
Facility Name
Santa Casa de Passos
City
Passos
State/Province
MG
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
Santa Casa de Santos
City
Santos
State/Province
SP
Country
Brazil
Facility Name
BP Mirante
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
Associação Beneficente Síria - Hospital do Coração (HCor)
City
São Paulo
State/Province
SP
Country
Brazil
Facility Name
Hospital 9 de Julho
City
São Paulo
State/Province
SP
Country
Brazil
Facility Name
Hospital Alemão Oswaldo Cruz
City
São Paulo
State/Province
SP
Country
Brazil
Facility Name
Hospital Beneficência Portuguesa
City
São Paulo
State/Province
SP
Country
Brazil
Facility Name
Hospital M'Boi Mirim
City
São Paulo
State/Province
SP
Country
Brazil
Facility Name
Hospital Santa Paula
City
São Paulo
State/Province
SP
Country
Brazil
Facility Name
Santa Casa de Votuporanga
City
Votuporanga
State/Province
São Paulo
Country
Brazil
Facility Name
Hospital Israelita Albert Einstein
City
Sao Paulo
Country
Brazil

12. IPD Sharing Statement

Plan to Share IPD
No

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Leronlimab in Moderately Ill Patients With COVID-19 Pneumonia

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