Clinical trial NCT04901689: 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
Overall status: SUSPENDED
Phase: PHASE3
Conditions: COVID-19 Pneumonia
Keywords: COVID-19
Pneumonia
Leronlimab
Lead sponsor: Hospital Israelita Albert Einstein
Sponsor class: OTHER
Collaborators: name: CytoDyn, Inc.
First posted: 2021-05-25
Enrollment: 316
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Cumulative proportion of clinical recovery
timeFrame: 28 days
Secondary outcomes:
measure: Proportion of patients clinically recovered
timeFrame: At days 14, 28, 42, and 60
measure: All-cause mortality
timeFrame: At days 14, 28, 42, and 60
measure: Proportion of patients discharged alive
timeFrame: At days 14, 28, 42, and 60
measure: Clinical Status
timeFrame: Days 14, 28, 42, and 60
measure: Duration of invasive mechanical ventilation or ECMO
timeFrame: 28 days
measure: Length of hospital stay
timeFrame: 28 days
measure: Length of ICU stay
timeFrame: 28 days
Other outcomes:
Locations:
city: Ipiaú
country: Brazil
facility: Clinica São Roque
state: BA
city: Salvador
country: Brazil
facility: Santa Casa de Misericórdia da Bahia - Hospital Santa Izabel
state: BA
city: Brasilia
country: Brazil
facility: Hospital do Coração do Brasil
state: DF
city: Laranjeiras
country: Brazil
facility: Hospital Dr Jayme dos Santos Neves
state: ES
city: Passos
country: Brazil
facility: Santa Casa de Misericórdia de Passos
state: MG
city: Sao Paulo
country: Brazil
facility: Hospital 9 de Julho
state: Please Select
city: Rio De Janeiro
country: Brazil
facility: Hospital São Lucas Copacabana
state: RJ
city: Natal
country: Brazil
facility: Instituto Atena de Pesquisa Clínica
state: RN
city: Passo Fundo
country: Brazil
facility: Hospital São Vicente de Paulo
state: RS
city: Porto Alegre
country: Brazil
facility: Hospital Mãe de Deus
state: RS
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de Misericórdia Porto Alegre
state: RS
city: Aracaju
country: Brazil
facility: Centro de Pesquisa Clínica do Coração
state: SE
city: Barretos
country: Brazil
facility: Fundação PIO XII
state: SP
city: Bragança Paulista
country: Brazil
facility: Irmandade do Sr. Bom Jesus dos Passos da Santa Casa de Misericórdia de Bragança Paulista
state: SP
city: Campinas
country: Brazil
facility: Instituto de Pesquisa Clínica de Campinas
state: SP
city: Indaiatuba
country: Brazil
facility: Hospital Santa Ignes
state: SP
city: Sao Paulo
country: Brazil
facility: Hospital Alemão Oswaldo Cruz
state: SP
city: Sao Paulo
country: Brazil
facility: Hospital Beneficência Portuguesa
state: SP
city: São José Do Rio Preto
country: Brazil
facility: Fundação Faculdade Regional de Medicina de São José do Rio Preto
state: SP
city: São Paulo
country: Brazil
facility: BP Mirante
state: SP
city: Votuporanga
country: Brazil
facility: Santa Casa de Votuporanga
state: SP
city: Sao Paulo
country: Brazil
facility: Hospital Israelita Albert Einstein
city: São Paulo
country: Brazil
facility: Hospital M'Boi Mirim
Study officials:
References: