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
试验速览
- 阶段
- 3 期
- 状态
- 暂停
- 入组人数
- 612
- 试验地点
- 27
- 主要终点
- Cumulative incidence of death or respiratory failure until day 28
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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-
- •Hospitalization for less than 72 hours, receiving standard of care treatment for COVID-
- •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.
排除标准
- •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.
研究组 & 干预措施
Leronlimab
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.
干预措施: Leronlimab (Drug)
Placebo
Placebo subcutaneously once a week (up to 4 doses) until hospital discharge
干预措施: Placebo (Drug)
结局指标
主要结局
Cumulative incidence of death or respiratory failure until day 28
时间窗: 28 days
Rates of participants who attain categories 6, 7, or 8 on the eight-category ordinal scale within 28 days 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
次要结局
- Time to clinical recovery(28 days)
- Death or intubation until day 28(28 days)
- All-cause mortality(Days 14, 28, 42, and 60)
- Proportion of patients discharged alive(Days 14, 28, 42, and 60)
- Proportion of patients clinically recovered(Days 14, 28, 42, and 60)
- Clinical status(Days 14, 28, 42, and 60)
- Length of hospital stay(28 days)