A Phase 2b/3, Randomized, Double Blind, Placebo Controlled, Adaptive Design Study to Evaluate the Efficacy and Safety of Leronlimab for Patients With Severe or Critical Coronavirus Disease 2019 (COVID-19)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 484
- 试验地点
- 18
- 主要终点
- All-cause Mortality at Day 28
研究概览
简要总结
The purpose of this study was assess the safety and efficacy of leronlimab (PRO 140) administered as weekly subcutaneous injection in subjects with severe or critical COVID-19 disease.
详细描述
This was a Phase 2b/3, two-arm, randomized, double blind, placebo controlled, adaptive design multicenter study to evaluate the safety and efficacy of leronlimab (PRO 140) in patients with severe or critical symptoms of respiratory illness caused by coronavirus 2019 infection. Patients will be randomized to receive weekly doses of 700 mg leronlimab (PRO 140), or placebo. Leronlimab (PRO 140) and placebo will be administered via subcutaneous injection.
A single arm, non-randomized, open-label phase was added to the protocol after completion of enrollment in the randomized phase of the study.
The study had three phases: Screening Period, Treatment Period, and Follow-Up Period.
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)
盲法说明
Unblinded pharmacists at clinical sites were notified of the arm to which the subjects were enrolled for the randomized portion of the study in order to prepare the appropriate treatment.
There was no masking for the open-label portion of the study.
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 female adult ≥ 18 years of age at time of screening.
- •Subjects hospitalized with severe or critical illness caused by coronavirus 2019 infection as defined below:
- •A. Severe Illness:
- •- Diagnosed with COVID-19 by standard reverse transcriptase polymerase chain reaction (RT-PCR) assay or equivalent testing within 5 days of screening
- •Symptoms of severe systemic illness/infection with COVID-19:
- •- At least 1 of the following: fever, cough, sore throat, malaise, headache, muscle pain, shortness of breath at rest or with exertion, confusion, or symptoms of severe lower respiratory symptoms including dyspnea at rest or respiratory distress
- •Clinical signs indicative of severe systemic illness/infection with COVID-19, with at least 1 of the following:
- •- respiration rate (RR) ≥ 30, heart rate (HR) ≥ 125, saturated oxygen (SaO2) <93% on room air or requires > 2L oxygen by nasal canula (NC) in order maintain SaO2 ≥93%, PaO2/FiO2 <300 (ratio of partial pressure of oxygen in arterial blood to fraction of inspired oxygen)
- •- None of the following: Respiratory failure (defined by endotracheal intubation and mechanical ventilation, oxygen delivered by high-flow nasal cannula, noninvasive positive pressure ventilation, or clinical diagnosis of respiratory failure in setting of resource limitations), Septic shock (defined by systolic blood pressure (SBP) < 90 mm Hg, or Diastolic BP < 60 mm Hg), Multiple organ dysfunction/failure
- •B. Critical Illness:
- •- Diagnosed with COVID-19 by standard RT-PCR assay or equivalent testing within 5 days of screening
- •Evidence of critical illness, defined by at least 1 of the following:
- •- Respiratory failure defined based on resource utilization requiring at least 1 of the following: Endotracheal intubation and mechanical ventilation, oxygen delivered by high-flow nasal cannula, noninvasive positive pressure ventilation, extracorporeal membrane oxygenation (ECMO), or clinical diagnosis of respiratory failure (in setting of resource limitation)
- •- Shock (defined by SBP < 90 mm Hg, or Diastolic BP < 60 mm Hg or requiring vasopressors)
- •Multiple organ dysfunction/failure
- •Subject, if intubated, positive end expiratory pressure (PEEP) <15 cmH2O with PaO2/FiO2 >150 mmHg.
- •Electrocardiogram (ECG) with no clinically significant findings as assessed by the Investigator
- •Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures.
- •Understands and agrees to comply with planned 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 with do-not-resuscitate (DNR) and/or do-not-intubate (DNI) orders or expected to be made DNR/DNI in setting of resource limitations or family wishes.
- •Not a candidate for dialysis or continuation of care (or full medical support) in setting of resource limitations.
- •Subject on continuous vasopressors (at the dose of norepinephrine >20μg/min and/or vasopressin >0.04 units/kg/min) for >48 hours at time of 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 or to comply with test requirements
- •Consideration by the investigator, for safety reasons, that the subject is an unsuitable candidate to receive study treatment
- •Pregnancy or breast feeding
- •Subject participating in another study with for an investigational treatment for COVID-
- •Note: Subject who were prescribed (1) hydroxychloroquine or chloroquine with or without azithromycin, (2) Remdesivir, (3) convalescent plasma therapy, or (4) immunomodulatory treatments (including but not limited to sarilumab, clazakizumab, tocilizumab, and anakinra) for the off-label treatment of COVID-19 prior to study enrollment may be included and may continue to receive these agents as part of standard-of-care.
研究组 & 干预措施
Placebo
Syringes containing normal saline for injection were prepared by an unblinded pharmacist at the clinical sites for use as the placebo.
干预措施: Placebo (Drug)
700mg Leronlimab
Each vial of active contains 350mg of leronlimab at a concentration of 175mg/ml (nominal 2mL fill volume) in formulation buffer containing histidine, glycine, sodium chloride, sorbitol, polysorbate 20 and sterile water for injections.
干预措施: Leronlimab (700mg) (Drug)
700mg Leronlimab Open Label
Each vial of active contains 350mg of leronlimab at a concentration of 175mg/ml (nominal 2mL fill volume) in formulation buffer containing histidine, glycine, sodium chloride, sorbitol, polysorbate 20 and sterile water for injections.
干预措施: Leronlimab (700mg) (Drug)
结局指标
主要结局
All-cause Mortality at Day 28
时间窗: Mortality at day 28 (Visit 2, start of treatment = day 0)
Incidence of mortality at day 28
次要结局
- All-cause Mortality at Day 14(Mortality at day 14 (initiation of treatment = day 0))
- Proportion of Patients Achieving a Category of 6 or Higher on the Ordinal Scale at Days 14 and 28 (on a 7 Point Ordinal Scale).(Change from baseline to days 14 and 28)
- Change in Clinical Status of Subjects at Day 28 (on a 7 Point Ordinal Scale)(Change from start of treatment (baseline) to day 28)
- Length of Hospital Stay(Timeframe is from screening visit to end of treatment (visit 5))