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Tocilizumab for Patients With Giant Cell Arteritis

2018年9月18日 更新者:University Hospital Inselspital, Berne

A Phase II, Randomized, Double-blind, Placebo Controlled Study of Tocilizumab in Patients With Giant Cell Arteritis

Giant-cell arteritis (GCA) is an immune-mediated disease that mostly affects people older than 50 years of age. Glucocorticoid (GC) treatment dramatically alters the symptoms and course of GCA, reducing the likelihood of vascular complications that could lead e.g. to blindness. However, relapses usually occur when GC dosages are tapered, resulting in frequent re-treatment with high cumulative dosages of GC over time with substantial toxicity and morbidity (e.g. diabetes mellitus, infections, enhanced cardiovascular risk, osteoporotic fractures, cataracts).

Therefore, novel therapies are needed that effectively reduce the dose and duration of GC treatment and provide more durable remissions of GCA.

Tocilizumab (TCZ) is a humanized monoclonal antibody directed against the human interleukin-6 receptor (IL-6R). Elevated tissue and serum levels of IL-6 have been implicated in giant cell arteritis. Inhibition of IL-6 and/or its receptor therefore represents a new and novel approach for the treatment of RA.

The primary endpoint is the proportion of patients that have achieved complete remission of disease after treatment with TCZ compared to treatment with placebo at week 12. All patients will receive glucocorticoids in a standardized form.

研究概览

详细说明

Background

Giant-cell arteritis (GCA) is an immune-mediated disease that mostly affects people older than 50 years of age. Glucocorticoid (GC) treatment dramatically alters the symptoms and course of GCA, reducing the likelihood of vascular complications that could lead e.g. to blindness. However, relapses usually occur when GC dosages are tapered, resulting in frequent re-treatment with high cumulative dosages of GC over time with substantial toxicity and morbidity (e.g. diabetes mellitus, infections, enhanced cardiovascular risk, osteoporotic fractures, cataracts).

Therefore, novel therapies are needed that effectively reduce the dose and duration of GC treatment and provide more durable remissions of GCA.

Tocilizumab (TCZ) is a humanized monoclonal antibody directed against the human interleukin-6 receptor (IL-6R). Elevated tissue and serum levels of IL-6 have been implicated in giant cell arteritis. Inhibition of IL-6 and/or its receptor therefore represents a new and novel approach for the treatment of RA.

Objective

The primary endpoint is the proportion of patients that have achieved complete remission of disease (normal ESR and CRP + absence of signs and symptoms) at Week 12 at a GC dose of 0.1 mg/kg/d of prednisone.

Methods

2-arm (Tocilizumab + Glucocorticoids (GCs) vs. Placebo + GCs), randomized, placebo-controlled, double blind, monocentric trial in patients with newly onset or relapsing giant cell arteritis (GCA), satisfying ACR criteria AND an elevated sedimentation rate above 40 mm/h and a CRP > 20 mg/L AND a biopsy proven GCA OR a large vessel vasculitis assessed by MR Angiography (MRA).

研究类型

介入性

注册 (实际的)

30

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习地点

      • Bern、瑞士、3010
        • Department of Rheumatology, Clinical Immunology Allergology, University Hospital, Inselspital

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

50年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  • Patients with newly onset or relapsed GCA
  • > 50 years of age
  • satisfying ACR criteria
  • elevated sedimentation rate above 40 mm
  • CRP > 20 mg/L
  • Patients with histologically proven GCA or with large vessel vasculitis assessed by MRI

Exclusion Criteria

  • Rheumatic diseases (except for CPPD/chondrocalcinosis) other than GCA/Takayasu disease or polymyalgia rheumatica (i.e., RA, autoimmune connectivitides, other systemic vasculitides, a.o.)
  • Evidence of significant and/or uncontrolled concomitant disease
  • Diagnosis of GCA > 4 weeks before screening visit and beginning of GC treatment > 4 weeks before screening (only valid for new onset GCA), or when a patient received treatment with tocilizumab or with other biological agents (such as TNFα-blockers) within 3 months before screening
  • Any condition or general state of health which, in the Investigator's opinion, would preclude participation in the study
  • Actual or recent myocardial infarction (within the last 3 months before screening visit)
  • Significant cardiac disease (NYHA Class III and IV), known severe chronic obstructive pulmonary disease (COPD) (FEV1 < 50% predicted or Functional dyspnoea > Grade 3 on the MRC Dyspnoea Scale) or other significant pulmonary disease
  • Uncontrolled disease (such as asthma, psoriasis or inflammatory bowel disease) where flares are commonly treated with oral or injectable corticosteroids
  • Known active infection of any kind, or any major episode of infection requiring hospitalization or treatment with i.v. anti-infectives within 4 weeks of baseline or completion of oral anti-infectives within 2 weeks prior to baseline
  • History of deep space/tissue infection (e.g. fasciitis, abscess, osteomyelitis) within 52 weeks prior to baseline
  • Any surgical procedure, including bone/joint surgery within 8 weeks prior to baseline or planned within the duration of the study
  • History of serious recurrent or chronic infection (for screening for a chest infection a chest radiograph will be performed at screening if not performed within 12 weeks prior to screening)
  • Lack of peripheral venous access
  • Body weight > 150 kg or BMI > 35
  • Previous treatment with tocilizumab or any other biological agent
  • Treatment with any investigational agent within 28 days of screening or 5 half-lives of the investigational drug (whichever is the longer)
  • History of severe allergic or anaphylactic reaction to any biologic agent or known hypersensitivity to any component of tocilizumab (RoActemra)
  • Receipt of any vaccine within 28 days prior to baseline (a patient's vaccination record and need for immunization prior to receiving tocilizumab/placebo must be carefully investigated)
  • Positive tests for hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (HbcAb) or hepatitis C serology
  • Positive Quantiferon-TB® test for latent Tb without subsequent INH prophylaxis
  • Patients with active Tb which had to be treated for Tb within 2 years before the screening visit

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

  • 主要用途:治疗
  • 分配:随机化
  • 介入模型:并行分配
  • 屏蔽:四人间

武器和干预

参与者组/臂
干预/治疗
实验性的:Tocilizumab
Tocilizumab 8mg/kg every 4 weeks until week 52.
Tocilizumab 8mg/kg every 4 weeks until week 52.
安慰剂比较:Placebo
Placebo every 4 weeks until week 52.
Placebo every 4 weeks until week 52.

研究衡量的是什么?

主要结果指标

结果测量
大体时间
Number of Patients That Have Achieved Complete Remission of Disease
大体时间:12 weeks
12 weeks

次要结果测量

结果测量
措施说明
大体时间
Number of Relapse Free Patients
大体时间:12 months
12 months
Cumulative Dose of GCs in mg/kg
大体时间:12 months
cumulative weight-adapted prednisolone dose
12 months
Restricted Mean Survival Time to First Relapse After Induction of Remission
大体时间:12 months
12 months

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

调查人员

  • 首席研究员:Peter M Villiger, Prof、Department of Rheumatology, Clinical Immunology Allergology, University Hospital, Inselspital
  • 首席研究员:Michael Seitz, Prof、Department of Rheumatology, Clinical Immunology Allergology, University Hospital, Inselspital

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始

2011年9月1日

初级完成 (实际的)

2014年12月1日

研究完成 (实际的)

2015年9月1日

研究注册日期

首次提交

2011年10月3日

首先提交符合 QC 标准的

2011年10月11日

首次发布 (估计)

2011年10月12日

研究记录更新

最后更新发布 (实际的)

2019年2月12日

上次提交的符合 QC 标准的更新

2018年9月18日

最后验证

2018年9月1日

更多信息

此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.

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