A Randomized, Double-blind, Parallel, Placebo-controlled Trial to Evaluate the Efficacy of Tocilizumab for the Treatment of Primary Sjögren's Syndrome.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 110
- 试验地点
- 1
- 主要终点
- Improvement of the ESSDAI score equal to or greater than 3 points compared to enrollment.
研究概览
简要总结
Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterized by lymphocytic infiltration leading to destruction of acinar and ductal cells and loss of glandular parenchyma. The main symptoms of pSS are dry eyes and dry mouth, diffuse pain, and fatigue. One third of patients develop systemic features, the most severe being lymphomas.
Serum IL-6 is increased in serum, saliva, and tears of patients with pSS. IL-6 plays a pivotal role in B-cell activation, a hallmark of the pathogenesis of pSS, and in T-cell differentiation. Tocilizumab, a recombinant humanised monoclonal antibody acts as an IL-6R antagonist. The aim of this randomised double blind placebo controlled trial iss to evaluate the efficacy of tocilizumab for the treatment of pSS.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient with primary Sjögren's syndrome according to the European - American consensus group criteria.
- •ESSDAI score ≥
- •In women in childbearing age, effective contraception during treatment and 3 months following treatment discontinuation.
排除标准
- •Patient with previous history of therapy with tocilizumab.
- •Prednisone treatment introduced two weeks before inclusion or a change in this drug dose within two weeks before inclusion.
- •A prednisone dose ≥ 15 mg per day.
- •Non-steroidal anti-inflammatory drugs, pilocarpine hydrochloride, cyclosporine, cimeviline if introduced within two weeks before inclusion.
- •Therapy with methotrexate, Hydroxychloroquine, chloroquine, quinacrine, leflunomide, psychoactive drug if introduced within 8 weeks before inclusion or a dose change within 8 weeks before inclusion.
- •Treatment with azathioprine or mycophenolate mofetil within 8 weeks before inclusion.
- •Live and live attenuated vaccines given within 4 weeks before inclusion.
- •Any biologic treatment within 6 month before inclusion.
- •Treatment with cyclophosphamide, intravenous immunoglobulin therapy or plasmapharese therapy in the last 6 months before inclusion.
- •Systemic auto-immune disease.
- •Patient with previous history of diverticular perforations, complications of diverticulitis, peritonite or inflammatory bowel disease (such as Crohn's disease and Colitis ulcerative).
- •Patient with history of severe infection within 4 weeks before inclusion.
- •Patient with history of infection within 2 weeks before inclusion.
- •Patient with chronic infection or infection returns (e.g. tuberculose, VHB, VHC…).
- •Positive serology tests for HIV, HBV, HCV.
- •Severe uncontrolled dyslipidemia.
- •Hepatocellular insufficiency.
- •Unstable cardiovascular disease.
- •Severe or chronic kidney disease, severe or chronic lung disease, severe or chronic endocrine disorder, severe or chronic neurological disease ( not related to the SJP).
- •Patient with history of solid organ transplantation or haematopoietic stem cell transplantation.
- •Patient with history of lymphoma, neoplasia diagnosed 5 years before inclusion except squamous and basal cell cancers and carcinoma in situ of the uterine cervix.
- •Severe complications of SJp at the inclusion: vasculitis with renal neurologic, digestive or cardiac involvement, interstitial lung disease, symptomatic cryoglobulinemia with severe neurologic involvement, renal function impairment, severe myositis, corticotherapy ≥ 1 mg/kg in the last 30 days before inclusion.
- •Neutropenia < 1000*10^6 .
- •Thrombocytopenia < 50 000/µl
- •ALT or AST > 3 x ULN
- •alcohol and drug addiction : withdrawal at least one year before inclusion
- •A major surgical procedure in the 8 weeks before inclusion or a scheduled major surgery
- •Pregnant woman, breast feeding woman
- •Adults under supervision or guardianship
- •Patient taking part in another clinical trial
研究组 & 干预措施
Tocilizumab arm
Tocilizumab arm will receive tocilizumab.
干预措施: Tocilizumab (Drug)
Placebo arm
Placebo arm will receive placebo.
干预措施: Placebo (Drug)
结局指标
主要结局
Improvement of the ESSDAI score equal to or greater than 3 points compared to enrollment.
时间窗: 24 weeks
Improvement of the ESSDAI score equal to or greater than 3 points compared to enrollment, with no new domain with high activity of the ESSDAI compared to enrollment, and no clinical worsening according to the clinician (no worsening compared to enrollment greater than 1 point of the Systemic Activity 0-10 VAS according to the physician.
次要结局
未报告次要终点