Efficacy, Safety, and Tolerability of Infliximab (Remicade; Schering-Plough) in Juvenile Spondyloarthropathies: a Three-Month, Randomized, Double-Blind, Placebo-Controlled Trial and 52-Week Open Extension.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Number of joints with active arthritis.
研究概览
简要总结
Tumor necrosis factor (TNF) alpha is a pro-inflammatory cytokine playing a significant role in the pathogenesis of the spondyloarthropathies (SpA). Infliximab is a TNF alpha blocking monoclonal antibody efficacious and safe as treatment of adult-onset SpA.
In this study we will try to demonstrate that infliximab administered at 5mg/kg to patients with juvenile onset SpA over a period of 12 weeks will have more efficacy than placebo and that it will be well tolerated. At the end of this phase, patients will go into a 52-week open extension to demonstrate sustained efficacy, safety, and tolerability of infliximab We will include 34 patients with juvenile onset SpA unresponsive to standard treatment. Efficacy will be assessed by counting the number of actively inflamed joints and a number of other parameters.
详细描述
Background Tumor necrosis factor (TNF) alpha is a pro-inflammatory cytokine playing a significant role in the pathogenesis of the spondyloarthropathies (SpA). Infliximab is a TNF alpha blocking monoclonal antibody efficacious and safe as treatment of adult-onset SpA.
Hypothesis Infliximab will reduce the number of joints with active arthritis and improve additional parameters of disease activity and functioning more significantly than placebo over 12 weeks. Infliximab will demonstrate sustained efficacy and its administration will be safe and well tolerated over 52 weeks.
Objectives To demonstrate superior clinical efficacy with infliximab administered at 5mg/kg compared with placebo, in juvenile onset SpA over a period of 12 weeks. To demonstrate sustained efficacy, safety, and tolerability of infliximab at 5 mg/kg over 52 weeks.
Study Design This is a two-phase study. First phase: 12-week, randomized, double-blind, placebo-controlled period to evaluate efficacy, safety, and tolerability of infliximab 5 mg/kg.
Thirty-four patients allocated and randomized to infliximab 5 mg/kg or placebo. Randomization: restricted by blocks of four and by stratification in two diagnostic categories (undifferentiated SpA and ankylosing spondylitis). Efficacy analysis: change of the primary efficacy measure and secondary measures on weeks 2, 6, and 12, and any visit of discontinuation compared to week 0 and compared to changes in the placebo group.
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)
入排标准
- 年龄范围
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ages less tha 16 years at symptoms onset and less than 18 years at entry
- •SpA diagnoses (ESSG criteria)
- •Active arthritis at least 2 peripheral joints
- •Pressure tenderness at least 3 peripheral entheses
- •Pain intensity of 40 mm in an analogue visual scale (VAS)
- •Lack of response to NSAID, sulfasalazine or methotrexate
- •Serum HCG-beta levels congruent with no pregnancy
- •Use of double-barrier contraceptive methods
- •History of BCG vaccination
- •Capacity to understand the study and follow protocol instructions
- •Written and signed consent letter.
- •Exclusion criteria:
- •Pregnancy and lactation
- •Mental disability
- •Functional class IV
- •Psoriasis, reactive arthritis or inflammatory bowel disease
- •Infectious, neoplastic, metabolic, hepatic, hematological, vascular, cardiopulmonary or renal active diseases
- •Opportunistic infectious
- •Active tuberculosis
- •Significant laboratory tests abnormalities
- •Current prednisone dose of more than 10 mg/day;
- •Intraarticular/muscular/venous glucocorticoids
- •Previous use of Infliximab or etanercept, pentoxyphylline, thalidomide, or anti-CD4 antibodies
- •Allergy or hypersensitivity to infliximab
- •Significant drug changes within one month before screening
- •Use of recreational drugs/illicit substances.
排除标准
- 未提供
研究组 & 干预措施
A
Infliximab
干预措施: infliximab (Drug)
B
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Number of joints with active arthritis.
时间窗: 12 weeks
次要结局
- Number of tender entheses; patient assessment of pain; patient/parent assessment of well being; investigator assessments of disease activity and health status; childhood health assessment questionnaire; and C reactive protein. Safety issues(12 weeks)