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

Sponsor

Hospital Israelita Albert Einstein (Other)

Overall Status

Suspended

CT.gov ID

NCT04901689

Collaborator

CytoDyn, Inc. (Industry)

316

Enrollment

Locations

Arms

15.3

Anticipated Duration (Months)

13.7

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

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).

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.

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 Design

Study Type:

Interventional

Anticipated Enrollment :

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

Actual Study Start Date :

Oct 23, 2021

Anticipated Primary Completion Date :

Feb 1, 2023

Anticipated Study Completion Date :

Feb 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Leronlimab (700 mg) Leronlimab 700 mg intravenously once a week (up to 4 doses) until hospital discharge	Drug: Leronlimab Leronlimab 700 mg
Placebo Comparator: Placebo Placebo intravenously once a week (up to 4 doses) until hospital discharge	Drug: Placebo Placebo

Arm

Intervention/Treatment

Experimental: Leronlimab (700 mg)

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

Drug: Leronlimab

Leronlimab 700 mg

Placebo Comparator: Placebo

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

Drug: Placebo

Placebo

Outcome Measures

Primary Outcome Measures

Cumulative proportion of clinical recovery [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: 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 [At days 14, 28, 42, and 60]
Ordinal Scale of 1, 2 or 3
All-cause mortality [At days 14, 28, 42, and 60]
All-cause mortality
Proportion of patients discharged alive [At days 14, 28, 42, and 60]
Ordinal Scale 1 or 2
Clinical Status [Days 14, 28, 42, and 60]
Ordinal Scale
Duration of invasive mechanical ventilation or ECMO [28 days]
Days
Length of hospital stay [28 days]
Days
Length of ICU stay [28 days]
Days

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country
1	Clinica São Roque	Ipiaú	BA	Brazil
2	Santa Casa de Misericórdia da Bahia - Hospital Santa Izabel	Salvador	BA	Brazil
3	Hospital do Coração do Brasil	Brasilia	DF	Brazil
4	Hospital Dr Jayme dos Santos Neves	Laranjeiras	ES	Brazil
5	Santa Casa de Misericórdia de Passos	Passos	MG	Brazil
6	Hospital 9 de Julho	Sao Paulo	Please Select	Brazil
7	Hospital São Lucas Copacabana	Rio De Janeiro	RJ	Brazil
8	Instituto Atena de Pesquisa Clínica	Natal	RN	Brazil
9	Hospital São Vicente de Paulo	Passo Fundo	RS	Brazil
10	Hospital Mãe de Deus	Porto Alegre	RS	Brazil
11	Irmandade da Santa Casa de Misericórdia Porto Alegre	Porto Alegre	RS	Brazil
12	Centro de Pesquisa Clínica do Coração	Aracaju	SE	Brazil
13	Fundação PIO XII	Barretos	SP	Brazil
14	Irmandade do Sr. Bom Jesus dos Passos da Santa Casa de Misericórdia de Bragança Paulista	Bragança Paulista	SP	Brazil
15	Instituto de Pesquisa Clínica de Campinas	Campinas	SP	Brazil
16	Hospital Santa Ignes	Indaiatuba	SP	Brazil
17	Hospital Alemão Oswaldo Cruz	Sao Paulo	SP	Brazil
18	Hospital Beneficência Portuguesa	Sao Paulo	SP	Brazil
19	Fundação Faculdade Regional de Medicina de São José do Rio Preto	São José Do Rio Preto	SP	Brazil
20	BP Mirante	São Paulo	SP	Brazil
21	Santa Casa de Votuporanga	Votuporanga	SP	Brazil
22	Hospital Israelita Albert Einstein	Sao Paulo		Brazil
23	Hospital M'Boi Mirim	São Paulo		Brazil