A Phase 2, Proof of Concept, 52-Week Open Study to Evaluate the Efficacy and Safety of Belimumab (HGS1006, LymphoStat-B™), a Fully Human Monoclonal Anti-BLyS (BAFF) Antibody, in Subjects With Primary Sjögren's Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- response rate
研究概览
简要总结
Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by an increase in BAFF (BLyS) levels and a resulting B cell hyperactivity. B cells are involved in the pathogenesis of SS in both systemic and glandular features, and B cell downregulation may lead to a decrease of disease activity. Moreover, pathogenesis of SS is closed to that of Systemic lupus erythematosus, where Belimumab has been proven to be effective.
详细描述
Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by an increase in BAFF (BLyS) levels and a resulting B cell hyperactivity. B cells are involved in the pathogenesis of SS in both systemic and glandular features, and B cell downregulation may lead to a decrease of disease activity. Moreover, pathogenesis of SS is closed to that of Systemic lupus erythematosus, where Belimumab has been proven to be effective.
This phase II open-label study has 2 mains objectives:
- To evaluate the proof of concept of efficacy of belimumab in subjects with SS
- To evaluate the safety and tolerability of belimumab in subjects with SS Belimumab will be administered (10mg/kg on D0 D14 D28 and every 28 days for 24 weeks, with extension to 48 weeks if responders) to all patients
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have a diagnosis of primary SS according to the updated American European Consensus Group Criteria. In addition, patients must be always positive for anti-SSA or anti-SSB antibodies
- •Have the presence, at screening, of Systemic involvement (polysynovitis, skin, renal, lung, CNS involvement, peripheral neuropathy, vasculitis, autoimmune cytopenia, defined in Annex 1) or persistent (up to 2 months) parotid, submandibular or lachrymal gland swelling of more than 2 cm OR
- •Objective sicca (positive oral and/or ocular tests reported in the American European Consensus Group Criteria) with at least one among the following biological features of serum B lymphocyte activation :
- •increased IgG levels increased free light chain levels of immunoglobulins (according to central laboratory ranges) increased serum beta2-microglobulin levels decreased C4 levels (C4 levels inferior to central laboratory ranges) monoclonal gammapathy cryoglobulinemia OR
- •SS of more recent onset, i.e., less than 5 years of duration of symptoms, associated with:
- •oral or ocular dryness
- •musculoskeletal pain (i.e, 3 criteria for response as reported at page (ix-x), characterized by VAS score more than 50/100 in all the 3 fields.
排除标准
- •Any BLyS-targeted (BLyS-receptor fusion protein [BR3], TACI Fc, or belimumab) at any time.
- •Any of the following within 364 days of Day 0:
- •B-cell targeted therapy (eg, rituximab, other anti-CD20 agents, anti-CD22 [epratuzumab], anti-CD52 [alemtuzumab]
- •A biologic investigational agent other than B cell targeted therapy (eg, abetimus sodium, anti CD40L antibody [BG9588/ IDEC 131]).
- •4- Intravenous or oral cyclophosphamide within 180 days of Day
- •5- Any of the following within 90 days of Day 0:
- •Anti-TNF therapy
- •Interleukin-1 receptor antagonist
- •Abatacept
- •Interleukin-6 receptor antagonist
- •Intravenous immunoglobulin
- •Prednisone > 100 mg/day
- •Plasmapheresis.
- •9- Very severe SS disease.
- •10- Major organ or hematopoietic stem cell/marrow transplant.
- •11- Unstable or uncontrolled acute or chronic diseases not due to SS
- •13- History of malignant neoplasm within the last 5 years, except for adequately treated cancers of the skin (basal or squamous cell) or carcinoma in situ of the uterine cervix.
- •14- Required management of acute or chronic infections, as follows:
- •Currently on any suppressive therapy for a chronic infection
- •Hospitalization for treatment of infection within 60 days of Day
- •Use of parenteral (IV or IM) antibiotics
- •16- Historically or at screening positive test for HIV antibody, hepatitis C virus antibodies, or, hepatitis B surface antigen (HbsAg) (with or without positive serum HBV DNA), or antiHBcAg positivity (without anti-HbsAg positivity).
- •17- Grade 3 or greater laboratory abnormality based on the protocol toxicity scale except for the following that are allowed:
- •Stable Grade 3 prothrombin time (PT) secondary to warfarin treatment.
- •Stable Grade 3/4 proteinuria (≤ 6 g/24 hour equivalent by spot urine protein to creatinine ratio allowed). (mentioned earlier in Exclusion #8)
- •Stable Grade 3 neutropenia or stable Grade 3 white blood cell count.
研究组 & 干预措施
1: Belilumab
干预措施: Belimumab (Drug)
结局指标
主要结局
response rate
时间窗: week 28
A response is defined as the fulfilment of any 2 of the 5 following response criteria(values are compared to that of baseline \[Day0\]): * ≥ 30% reduction of the patient's dryness VAS * ≥ 30% reduction of the patient's fatigue VAS * ≥ 30% reduction of the patient's musculoskeletal pain VAS * ≥ 30% reduction of the physician's systemic activity VAS * ≥ 25% reduction of serum levels of any of the following B cell activation biomarkers (free light chains of immunoglobulin, beta2-microglobulin, monoclonal component, cryoglobulinemia, IgG) or ≥ 25% C4 increase
次要结局
- safety and tolerability of belimumab(52 weeks)