Subcutaneous and Intravenous IL-1Ra (Anakinra) in COVID-19 Infection - Feasibility & Pharmacokinetics/Pharmacodynamics Study
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 2
- 主要终点
- Plasma IL-1Ra levels
研究概览
简要总结
The current COVID-19 pandemic is a worldwide healthcare crisis. Of concern is the large number of patients that are/will require mechanical ventilation, and the associated strain that this will place on healthcare resources. At present, there are no specific therapeutic interventions directed at COVID-19 infection. However, observational data suggest that there is a subgroup of patients that demonstrate a hyperinflammatory response in response to COVID-19 and have a higher requirement for Critical Care and higher mortality.
There is a strong case for the use of the naturally occurring anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1Ra) in these patients. Anakinra is a recombinant form of IL-1Ra that is licensed for clinical use. Success of use of anakinra in COVID-19 trials will be greatly enhanced by robust scientific evidence and established pharmacokinetics which inform the most effective dosing regimens. The latter is especially important when, as in the case of anakinra, drug supplies are limited, the drug has short half-life and clinical ease of application is critical.
详细描述
The investigators plan a small trial of an existing drug in patients with COVID-19 at Salford Royal NHS Foundation Trust (SRFT) and Manchester Foundation Trust (MFT). The investigators will recruit patients with suspected or confirmed COVID-19 infection within 24 hours of being transfer in a Critical Care department. The investigators have been testing interleukin-1 receptor antagonist: IL-1Ra (known as Anakinra) for many years. Marketed as a treatment for rheumatoid arthritis and for some rare autoimmune diseases, we have shown Anakinra also reduces or blocks inflammation in a number of other conditions e.g. stroke and brain haemorrhage. The investigators have found it to be safe, easily administered and well tolerated. As part of the global response to the SARS-COV-2 pandemic, researchers have identified drugs that repurposing existing drugs. Anakinra has been proposed as a candidate therapy for COVID-19 and will be used in REMAP-CAP clinical trial as an intravenous (IV) therapy four times daily (qds). Whilst there is uncertainty about the therapeutic benefits, the investigators wish to explore the theory that they can achieve comparable concentrations in the blood using a subcutaneous (SC) injection twice daily (bd), as observed with IV therapy qds. We will randomise up to 40 patients to receive either SC Anakinra twice daily or IV Anakinra four-times daily for 14 days (or until discharge from CCU). They will measure changes in biomarkers in both groups and use the data to inform a mathematical model to simulate the effect the drug may have on the body. The aim is to the provide evidence that a lower dose SC Anakinra is as effective as higher dose IV.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Health Services Research
- 盲法
- None
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
- •Patient age 18 or above.
- •Clinically suspected/proven COVID-
- •Requiring organ support with one or more of:
- •Non-invasive or invasive ventilatory support
- •Receiving infusion of vasopressor or inotropes or both.
- •No concomitant health problems that, in the opinion of the PI or designee in agreement with the treating clinician, would interfere with participation, administration of study drug or assessment of outcomes including safety.
排除标准
- •More than 24h has elapsed since CCU admission.
- •Death is deemed to be imminent and inevitable during the next 24h.
- •One or more of: the patient, substitute decision-maker or the attending physician are not committed to full active treatment.
- •Known condition resulting in ongoing immunosuppression including neutropenia (count < 1.5 x 10^9/L) prior to hospitalisation, malignancy, latent tuberculosis or chronic liver disease (if known).
- •Previous or current treatment with anakinra or medication suspected of interacting with anakinra, listed in the drug SmPC, known at the time of trial entry or previous participation in this trial.
- •Known to have received active treatment in a clinical trial of an investigational immunomodulatory agent (not including corticosteroids) within 30 days prior to study entry.
- •Known to be pregnant or breast feeding or inability to reliably confirm that the patient is not pregnant.
- •Known allergy to anakinra or any of the excipients listed in the drug SmPC
- •Known allergy to other products that are produced by DNA technology using the micro-organism E. coli (e.g. Escherichia coli derived protein).
研究组 & 干预措施
Subcutaneous Arm
100mg anakinra SC will be administered subcutaneously at consistent times that are convenient and practical for the patients and research/nursing staff providing there is a minimum 8 hours and maximum 16 hours between administrations.
干预措施: Anakinra 100Mg/0.67Ml Inj Syringe (Drug)
Intravenous Arm
100mg anakinra in 100mL 0.9% NaCl will be administered intravenously four times a day every 6 hours.
干预措施: Anakinra 100Mg/0.67Ml Inj Syringe (Drug)
结局指标
主要结局
Plasma IL-1Ra levels
时间窗: 1 week
Plasma IL-1Ra levels from Day 1 to Day 7 following administration of SC anakinra in patients with SARS-CoV-2
Plasma IL-6 levels
时间窗: 1 week
Plasma IL-6 levels from Day 1 to Day 7 following administration of SC anakinra in patients with SARS-CoV-2
次要结局
- Plasma markers(2 weeks)
- Exploratory Data on Clinical efficacy of the ordinal scale(4 weeks)
- Feasibility endpoints related to IMP and deviations(2 weeks)
- Safety Endpoints related to the anaphylactic reactions of the IMP(2 weeks)
- Exploratory Data on Clinical efficacy(4 weeks)
- Safety Endpoints related to the Serious adverse reactions of the IMP(2 weeks)
- Safety Endpoints related to any severe laboratory abnormalities(2 weeks)
- Exploratory Data on Clinical efficacy by time to recovery(4 weeks)
- Safety Endpoints related to neutropenia caused by the IMP(2 weeks)