A Phase II, Randomized, Multi-Center, Double-Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of BMS-931699 (Lulizumab) or BMS-986142 in Subjects With Moderate to Severe Primary Sjögren's Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 45
- 试验地点
- 15
- 主要终点
- Mean Change From Baseline in ESSDAI
研究概览
简要总结
The primary objective of this study is to evaluate the efficacy of treatment with either lulizumab or BMS-986142 versus placebo in subjects with moderate to severe primary Sjögren's syndrome as measured by the change from baseline in ESSDAI at Week 12 between active treatment arms (lulizumab or BMS-986142, respectively) and the placebo arm.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects diagnosed or classified as having moderate to severe primary Sjögren's Syndrome based on the 2016 ACR-EULAR Sjögren's Syndrome Classification Criteria for at least 16 weeks prior to screening
- •ESSDAI ≥ 5 including disease activity (any score > 0) in at least one of the following domains: Glandular, Articular, Hematological, Biological, Lymphadenopathy
- •Positive anti-SS-A/Ro and/or anti-SS-B/La autoantibody
- •Unstimulated whole saliva secretion > 0.01 ml/min
- •Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug and must not be pregnant or breastfeeding. Male and female subjects must be willing to adhere to protocol-mandated highly effective contraception for the duration of the study and for the protocol-specified follow up period. Hormone-based contraceptive methods are not permitted
排除标准
- •Secondary Sjögren's syndrome or the presence of any other systemic autoimmune disease (eg, RA, SLE, multiple sclerosis, vasculitis)
- •Very severe primary Sjögren's syndrome or severe complications of primary Sjögren's syndrome at the time of the screening visit
- •Active systemic or latent bacterial (including tuberculosis), viral or fungal infection, evidence of current or chronic Hepatitis B or C infection, or HIV infection
- •Any significant concurrent medical condition at the time of screening or baseline visit
- •Use of methotrexate, cyclophosphamide, cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil (MMF) or leflunomide within 12 weeks of screening visit
- •Previous treatment with biologics therapies either marketed or in development within 6 months prior to screening visit
- •Treatment started or an unstable dose of hydroxychloroquine within 8 weeks of screening visit
- •Oral corticosteroids > 10 mg/day within 14 days of dosing (Day 1), corticosteroid therapy ≥ 1 mg/kg during the 4 weeks preceding enrollment, or intravenous, intramuscular or intra-articular corticosteroids within 4 weeks of screening visit
- •Other protocol defined inclusion/exclusion criteria could apply
研究组 & 干预措施
Placebo
Weekly subcutaneous placebo injection +daily oral placebo tablets
干预措施: Placebo (Drug)
BMS-931699
Subcutaneous weekly injection + daily oral placebo tablets
干预措施: BMS-931699 (Drug)
BMS-931699
Subcutaneous weekly injection + daily oral placebo tablets
干预措施: Placebo (Drug)
BMS-986142
Daily oral tablets + subcutaneous placebo (weekly) injection
干预措施: BMS-986142 (Drug)
BMS-986142
Daily oral tablets + subcutaneous placebo (weekly) injection
干预措施: Placebo (Drug)
结局指标
主要结局
Mean Change From Baseline in ESSDAI
时间窗: At baseline and week 12
The ESSDAI is a clinical index that measures Sjogren's syndrome disease activity. A physician scores the disease activity level of twelve organ-specific domains in 3 or 4 levels according to their severity. For example, for no disease activity the domain score equals 0 and for high disease activity the domain score equals 3 or 4. Each domain is assigned a weight between 1 and 6, and the domain score is multiplied by the domain weight. The sum of the weighted domain scores is the overall score, which can range from 0 to 123. A higher score indicates more disease activity. Change from baseline was computed as the value at Week 24 minus the baseline value. A negative value in change from baseline indicates an improvement and a positive value indicates worsening
次要结局
- Mean Change From Baseline in ESSDAI Scores at Week 4 and Week 8(At baseline, week 4 and week 8)
- Proportion of Subjects With a > = 3 Point Improvement From Baseline in ESSDAI at Week 12(At week 12)
- Proportion of Subjects With Both >= 3 Points Improvement in ESSDAI and >= 1 Point Improvement in ESSPRI From Baseline at Week 12(At week 12)
- Mean Change in Baseline in ESSPRI Individual Component of Pain(At baseline, week 4, week 8, and week 12)
- Mean Change From Baseline in Ocular Surface Staining(At baseline, week 4, week 8, and week 12)
- Mean Change From Baseline in Unstimulated Salivary Flow Rate(At baseline, week 4, week 8, and week 12)
- Mean Change From Baseline in Short Form-36 (SF-36)(At baseline, week 4, week 8, week 12, and week 18)
- Mean Change From Baseline in Stimulated Salivary Flow Rate(At baseline, week 4, week 8, and week 12)
- Mean Change Form Baseline in Physician Global Assessment of Disease Activity (phyGDA)(At baseline, week 2, week 4, week 6, week 8, week 10, week 12, and week 18)
- Mean Change From Baseline in ESSPRI Score at Week 4, Week 8, and Week 12.(At baseline, week 4, week 8, and week 12)
- Mean Change in Baseline in ESSPRI Individual Component of Dryness(At baseline, week 4, week 8, and week 12)
- Mean Change in Baseline in ESSPRI Individual Component of Fatigue(At baseline, week 4, week 8, and week 12)
- Mean Change From Baseline in Schrimer's Test(At baseline, week 4, week 8, and week 12)
- Proportions of Subjects With >=1 Point of Improvement From Baseline in ESSPRI(At week 12)
- Mean Change From Baseline in the Tear Break-up Time Test(At baseline, week 4, week 8, and week 12)
- Mean Change From Baseline in Numeric Rating Scale (NRS) for Mouth, Eye and Vaginal Dryness(At baseline, at week 2, week 4, week 6, week 8, week 10, week 12, and week 18)
- Mean Change From Baseline in Subject Global Assessment of Disease Activity (SubGDA)(At baseline, week 2, week 4, week 6, week 8, week 10, week 12, and week 18)
- Mean Change From Baseline in Female Sexual Function Index (FSFI)(At baseline, week 4, week 8, week 12, and week 18)
- Mean Change From Baseline in Work Participation and Activity Impairment Questionnaire (WPAI)(At baseline, week 4, week 8, week 12, and week 18)