A Therapeutic Open Label Study of Tocilizumab in the Treatment of Pulmonary Arterial Hypertension
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- Pulmonary vascular resistance- dynes (cm-5)
研究概览
简要总结
An open label study to assess the safety and efficacy of tocilizumab in group 1 pulmonary arterial hypertension patients
详细描述
In Pulmonary Arterial Hypertension (PAH) raised blood pressure in the lungs leads to heart failure and early death. Patients not only have a significantly reduced life expectancy, but their quality of life is severely affected. If left untreated life expectancy is 2-3 years. Current treatments all aim to relax the vessels in the lung and lower the blood pressures, however none target the causes of the disease and currently there is not cure. Despite the availability of treatments the impact on mortality has been modest at best with one third of patients still dying within two years of diagnosis. There remains an urgent need to test new ways of treating PAH.
PAH is often associated with auto-immune diseases (when the bodies own system attacks itself rather than fight infection). Targeting components of the immune system involved in the development of disease offer a potential new area of treatment for PAH; an example known to be involved in the progression of PAH is the protein Interleukin-6 (IL-6). Tocilizumab is a drug which blocks the action of Interleukin-6 and blocking Interleukin-6 has been shown to be effective in animal models of PAH. Tocilizumab was demonstrated to be safe and effective in trials in other diseases associated with PAH, such as rheumatoid arthritis.
This study is a 6 month open label phase II trial of IV Tocilizumab in 21 patients with group 1 PAH. The aim of the trial is to see if Tocilizumab is safe and whether it reduces the blood pressure in the lungs. Patients will be given Tocilizumab intravenously once a month for six months with close safety monitoring. The trial will be led by Papworth Hospital and a total of 7 UK specialist centres will take part. The trial will assess the safety of the drug and response to treatment by measuring heart function, blood pressure in the lungs, exercise capacity and quality of life measurements.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Group 1 PAH due to: Idiopathic or Heritable PAH, PAH associated with connective tissue disease excluding SLE, RA and mixed CTD, Drug and Toxins
- •WHO functional class II-IV
- •Weight more than 40kg
- •6 minute walk distance of 100-500 m
- •Haemodynamic criteria measure by RHC
- •Documented negative V/Q scan or pulmonary arteriogram confirming absence of chromic thromboembolic disease
- •Resting oxygen saturations of >85%
- •Lung function confirming absence of significant lung disease
- •Stable on unchanged PAH therapeutic regime for at least 1 month
排除标准
- •Subjects on continuous infusions either intravenously or subcutaneously
- •Hypersensitivity to Investigational Product
- •Severe hepatic impairment
- •Severe renal impairment
- •Clinically significant anaemia
- •Blood platelets <100x10
- •Neutrophil count <2x10/L
- •Left ventricular disease/dysfunction risk factors
- •Myocardial infarction within 90 days prior to screening
- •Female subjects who are pregnant or breastfeeding
- •History of malignancies within past 5 years
研究组 & 干预措施
Open Label
Intravenous Tocilizumab 8mg/kg monthly (up to a maximum dose 800mg) for 6 months
干预措施: Tocilizumab (Drug)
结局指标
主要结局
Pulmonary vascular resistance- dynes (cm-5)
时间窗: Change from baseline pulmonary vascular resistance to end of study at 6 months
Invasive haemodynamic assessment by right heart catheter
Safety - Incidence and severity of adverse events
时间窗: 6 months
Incidence and severity of treatment emergent adverse events
次要结局
- Six minute walk test(Baseline and every month for 6 months)
- World Health Organisation functional class assessment of patient reported symptoms(Baseline and every month for 6 months)
- Quality of Life(Baseline and every month for 6 months)
- N-Terminal pro-B-type Natriuretic Peptide(Baseline and every month for 6 months)