Randomized Controlled Study to Evaluate the Efficacy of Adalimumab in Patients With Different Forms of Refractory Uveitis Acronym: Adalimumab in Uveitis Refractory to Conventional Therapy (ADUR Trial)
试验速览
- 阶段
- 2 期
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Improvement of visual acuity (3 lines EDTRS)
研究概览
简要总结
TNF alpha Inhibitors have been very effective in treating rheumatologic diseases as well as uveitis. Adalimumab is the first member of a new class of TNF antibody compounds developed to contain exclusively human sequences. We want to test the efficacy and safety of the TNF alpha Inhibitor Adalimumab in patients with active uveitis despite standard immunosuppressive therapy.
详细描述
TNF alpha Inhibitors like Infliximab and Etanercept have been very effective in treating rheumatologic diseases. They have been used to treat severe uveitis by several groups, Suhler and coworkers have published the largest series in 2005. Adalimumab, a recombinant, full-length immunoglobulin, is the first member of a new class of TNF antibody compounds developed to contain exclusively human sequences. The duration of therapeutic efficacy of other TNF antibodies, which contain non-human sequences, may be limited to a greater extent by antibody responses raised in subjects over time. We want to test the efficacy and safety of the TNF alpha Inhibitor Adalimumab in patients with active uveitis despite standard immunosuppressive therapy requiring systemic corticosteroids > 7,5mg prednisolone.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
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
- •Male and female patients age 18 and older
- •Subjects must meet the criteria for non-infectious uveitis according to the definition of the SUN working group
- •Uveitis must have first been diagnosed at least 6 months ago
- •Persistence of active disease ( > 2 flares within 6 months) or progressive deterioration of vision (< 0,6) within the last 3 months despite immunosuppressive therapy requiring corticosteroids ≥ 7,5 mg prednisone
- •Women of childbearing potential have to practice a reliable birth control method throughout the study and until five months after the last administration of Adalimumab
- •Ability to comprehend and willing to give informed consent for participation in the study
- •Able and willing to self-administer sc injections or assistance of a suitable person to administer sc injections
- •Negative PPD skin test or serological testing according to official German recommendations for tuberculosis testing AND chest X-ray within the last three month. Treatment of latent TB with INH must be started 4 weeks prior to administration of first dose of study drug.
排除标准
- •Participation in another clinical trial and/or observation period of competing trials
- •Treatment with infliximab within the last 2 months or with etanercept within the last 3 weeks
- •Patients with only intermediary uveitis or optic neuritis multiple sclerosis
- •Patients with uveitis caused by infection
- •Patients with optic atrophy, macular scar, cataract, amblyopia or corneal scars
- •Patients with recurrent episodes of uveitis, but long intermittent phases of complete remissions without therapy
- •Patients possibly demanding vitrectomy or cataract surgery within the time of clinical trial
- •Pregnant and nursing women or women planning a pregnancy within 5 months
- •Persistent or recurrent infections or severe infections requiring hospitalization with iv antibiotics within 30 days, or oral antibiotics within 14 days prior to enrollment
- •Known opportunistic infection (such as herpes zoster) during the last 2 months
- •Live vaccination during the last 30 days
- •History of tuberculosis; histoplasmosis or listeriosis
- •Known HIV infection, active hepatitis B or C
- •Comorbidities: uncontrolled diabetes, unstable ischemic heart disease, congestive heart failure (NYHA III, IV), active inflammatory bowl disease, recent stroke (within three months), chronic leg ulcer and similar conditions which would put the subject at risk by participation in the trial
- •Previous diagnosis of signs of central nervous system demyelinating diseases
- •History of cancer or lymphoproliferative disease other than a successfully and completely treated squamous cell or basal cell carcinoma of the skin or cervical dysplasia, with no recurrence within the last two years
- •Hemoglobin < 10 g/dl, white blood cell count < 3.0x109/l, platelet count < 100x109/l, creatinine level >1.5 mg/dl, liver enzymes > 1.5 times above normal or alkaline phosphatase >3 times above normal
- •Clinical examination showing significant abnormalities of clinical relevance
- •Current evidence of significant abuse of drugs
- •Psychiatric disease/social situations that would limit compliance with study requirements
研究组 & 干预措施
Adalimumab + corticosteroids + immunosuppressive treatments
Adalimumab 40 mg eow, stable immunosuppression, corticosteroids in 1 mg/kg/Bodyweight (max. 80 mg) and taper
干预措施: Adalimumab (Drug)
immunosuppressive treatment + corticosteroids
corticosteroids upped to 1mg/kg/Bodyweight and taper, stable immunosuppressive treatment
干预措施: Adalimumab (Drug)
结局指标
主要结局
Improvement of visual acuity (3 lines EDTRS)
时间窗: at week 0, 2, 6, 12 and 24
次要结局
- Improvement of intraocular inflammatory activity(at week 0, 2, 6, 12 and 24)
- Evolution of cystoid macula edema(FLA, OCT)(at week 0, 6, 12 and 24)
- Number of switchers from Arm A to Arm B(after six months)
- Cumulative steroid dosage(after six months)
- Frequency of adverse events(whole study period)
研究者
Friederike Mackensen
PD Dr. med.
Heidelberg University