A Phase 2 Trial to Evaluate the Safety and Tolerability of Clazakizumab® [Anti-Interleukin (IL)-6 Monoclonal] Compared to Placebo for the Treatment of COVID-19 Infection
试验速览
- 阶段
- 2 期
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Primary Endpoint
研究概览
简要总结
The purpose of this study is to investigate the effectiveness and safety of treatment with clazakizumab compared to a placebo (inactive substance). We are proposing to try this drug to treat coronavirus disease 2019 (COVID-19) infection. Patients with COVID-19 infection have been shown to have increases in certain inflammatory processes. Clazakizumab is an antibody (immune system protein) that blocks certain inflammatory processes. The treatment plan is to attempt to inhibit or block these inflammatory processes in order to try to limit the damage COVID-19 causes to the lungs.
详细描述
The purpose of this randomized, double-blind, placebo-controlled trial is to evaluate the safety and efficacy of clazakizumab vs placebo for the prevention of acute respiratory distress syndrome (ARDS) in patients with COVID-19 and pulmonary manifestations. The study will compare clazakizumab to placebo in a randomized, double-blind fashion followed by an open-label dose of clazakizumab if there is no improvement or a worsening of condition occurs after 24-hours or anytime during the first 14 days after the first dose of clazakizumab or placebo. We hypothesize that clazakizumab will be safely tolerated and will reduce the risk of progression of COVID-19 to acute respiratory distress syndrome.
Primary Objective:
• To evaluate the safety and tolerability of clazakizumab vs placebo for the treatment of patients with COVID-19 disease and signs of pulmonary involvement
Sixty adult patients with COVID-19 and signs of pulmonary involvement at Houston Methodist who are not in need of ventilator support at the time of enrollment.
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
Blinded to all except investigational pharmacy. Only the optional second infusion, if determined necessary to administer, will be open-label. The patient and study team will remain blinded until data lock at the end 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
- •Age >18 at the time of screening.
- •Participant or legally authorized representative (LAR) must be able to understand and provide informed consent.
- •Hospitalized with coronavirus disease (COVID-19) confirmed by polymerase chain reaction (PCR) assay from any specimen (eg, respiratory, blood, urine, stool, other bodily fluid) within the prior 72 hours.
- •C-reactive protein (CRP) > 3.5 mg/dL
- •Evidence of pulmonary involvement with at least 2 of the following:
- •oxygen saturation at rest in ambient air with peripheral capillary oxygen saturation (SpO2) ≤ 94%
- •tachypnea with resting respiration rate > 25 breaths/minute
- •Partial pressure of oxygen (PaO2)/initial fraction of inspired oxygen (FiO2) ≤ 300 mmHg
- •Chest imaging (radiograph, CT, or ultrasound) with abnormalities consistent COVID-19 pneumonia
排除标准
- •Previous hypersensitivity or allergic reactions to clazakizumab
- •Lactating or pregnant females
- •Patients with latent tuberculosis (TB) and who are not receiving treatment
- •Patients with active TB
- •Patients with known active inflammatory bowel disease, untreated diverticulitis, or gastrointestinal perforation
- •Requiring mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
- •A significantly abnormal general serum screening lab result defined as a white blood cell (WBC) count < 3.0 X 10^3/mL, a hemoglobin (Hgb) < 8.0 g/dL, a platelet count < 50 X 10^3/mL, an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 times upper limit normal
- •Participation in another clinical trial investigating COVID-19-aimed agents
- •Presence of any medical or psychosocial condition, which the investigator believes, would hinder adherence to the study requirements.
研究组 & 干预措施
Clazakizumab
Clazakizumab - 25mg in 50 milliliters (mL) of 0.9% saline, IV infusion over 30 minutes.
干预措施: Clazakizumab (Drug)
Placebo
Placebo - 50 mL 0.9% saline, IV infusion over 30 minutes.
干预措施: Placebo (Drug)
结局指标
主要结局
Primary Endpoint
时间窗: 24 hours
Proportion of participants who experience treatment-related adverse events (TEAE) ≥ Grade 3 (CTCAE v5.0) during the first 24 hours after infusion of clazakizumab or placebo
次要结局
- Requirement for mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO)(14 days)
- Time in the hospital(60 days)
- Infusion-related reactions during 24 hours from the time of infusion(24 hours)
- Patient survival at 28 days(28 days)
- Patient survival at 60 days(60 days)
- Requirement for open-label clazakizumab(14 days)
- Time in the intensive care unit (ICU)(60 days)
- Time to mechanical ventilation(60 days)
- Clinical status improvement assessed by the World Health Organization (WHO) Clinical Progression Scale at day 14(14 days)
- Change in Radiologic Assessment of Lung Edema (RALE) at day 14(14 days)
- Clinical status improvement assessed by World Health Organization (WHO) Clinical Progression Scale at day 28(28 days)
- Change in Radiologic Assessment of Lung Edema (RALE) at day 28(28 days)