A Multicenter, Randomized, Double-blind, Placebo-controlled, Adaptively Designed Clinical Trial of the Efficacy and Safety of Levilimab (BCD-089) in Patients With Severe COVID-19
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Biocad
- 入组人数
- 206
- 试验地点
- 16
- 主要终点
- Proportion of patients with sustained clinical recovery
研究概览
简要总结
The objective: to study the efficacy and safety of levilimab in subjects with severe COVID-19.
详细描述
This study is multicenter, comparative, randomized, double-blind, placebo controlled clinical trial with adaptive design. Females and males, aged 18 years and older, admitted to hospital with severe COVID-19 pneumonia on SOC therapy will receive either levilimab 324 mg s/c or placebo s/c. In case of no clinical improvement is observed, investigator can administer a rescue therapy - open label LVL 324 mg s/c. The outcomes will be assessed up to day 60. Results of interim analysis of safety and efficacy data of first 60 enrolled subjects will be submitted for independent DMC review and decision about changes to the protocol.
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
- Double (Participant, Investigator)
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
- •Signed informed consent (subject; legally authorized representative) or signed conclusion of panel of independent medical doctors
- •Males and non-pregnant females aged 18 years or older at the IC date
- •Positive test for SARS-CoV2 nucleic acid (RNA) at the IC date
- •Admitted as inpatient to a hospital with radiologically confirmed pneumonia
- •Severe form of COVID-
- •Subjects meeting any of the following criteria:
- •Total respiratory rate > 30 breaths per minute
- •SpO2 ≤ 93%
- •PaO2 /FiO2 ≤ 300 mmHg
- •Chest imaging (X-ray, CT, US) showed lesion progression within 24-48 hours >50%
- •Decrease of consciousness level, Psychomotor agitation/irritability
- •Hemodynamically unstable (systolic blood pressure <90 mmHg or diastolic blood pressure < 60 mmHg or urine output < 20 ml/h)
- •Arterial lactate > 2 mmol/l
- •qSOFA (quick sequential organ failure assessment score) >
- •Subjects meeting three following criteria: Low blood pressure (SBP ≤ 100 mmHg); High respiratory rate (≥ 22 breaths/min); Altered mentation (Glasgow Coma Scale ≤ 14)
排除标准
- •Critical COVID-
- •Subjects meeting any of the following:
- •Respiratory failure and requiring invasive mechanical ventilation (tracheal intubation)
- •Septic shock
- •Multiple organ failure
- •Life expectancy < 24h, in the opinion of the investigator,
- •Unlikely to remain at the investigational site beyond 48 hours
- •Use of other monoclonal antibodies for COVID-19 treatment
- •Current treatment with immunosuppressive agents (including corticosteroids)
- •Participating in other drug clinical trials at the IC date or within 60 days after randomization (participation in COVID-19 anti-viral trials may be permitted if approved by Sponsor)
- •Laboratory values:
- •ALT / AST > 10 ULN at screening
- •Platelets < 50х109/l at screening
- •Absolute Neutrophil Count < 1х109/l at screening
- •Suspected active bacterial, fungal, viral, or other infection (besides COVID-19)
- •Confirmed active tuberculosis
- •History of allergic reaction to monoclonal antibodies
- •Pregnancy or breastfeeding
- •Any illness or laboratory findings that, in the opinion of the study investigator, might pose an additional risk to the patient by their participation in the study,
研究组 & 干预措施
Placebo group
Single subcutaneous administration of placebo in combination with standard therapy
干预措施: Placebo (Drug)
LVL group
Single subcutaneous administration of levilimab at a dose of 324 mg in combination with standard therapy
干预措施: Levilimab (Drug)
结局指标
主要结局
Proportion of patients with sustained clinical recovery
时间窗: Day 14
Sustained clinical recovery is defined as either an improvement of at least 2 categories relative to baseline on a 7-Category Ordinal Scale of Clinical Status or reaching categories "Discharged" / "Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care" at day 14.
次要结局
- Change in serum IL-6 level(Day 30)
- Proportion of patients reporting each category of 7-Category Ordinal Scale of Clinical Status(Day 30)
- Duration of fever(Day 60)
- Change in serum CRP level(Day 30)
- Proportion of patients transferred to the ICU(Day 60)
- Duration of hospitalization(Day 60)
- Change in ESR(Day 30)