A Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Phase 2A Study to Assess the Efficacy of RO5459072 in Patients With Primary Sjogren's Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 75
- 试验地点
- 31
- 主要终点
- Percentage of Participants With a Clinically Relevant Decrease in European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI) Score
研究概览
简要总结
This is a randomized, double-blind, placebo-controlled, two-treatment arm, parallel-group study designed to evaluate the effects of RO5459072 treatment on disease activity and symptoms of Sjogren's syndrome in adult participants with moderate to severe primary Sjogren's syndrome. The total duration of the study for each participant will be approximately 18 weeks (including screening).
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A diagnosis of primary Sjogren's syndrome according to the revised American-European Consensus Group (AECG) criteria
- •ESSDAI score greater than or equal to (>/=) 5
- •ESSPRI score >/=5
- •Elevated serum titers of anti-Sjogren's-syndrome-related antigen A (anti-SSA) and/or anti-Sjogren's-syndrome-related antigen B (anti-SSB) antibodies at screening
- •Negative pregnancy test at screening and baseline (for women only)
- •Willing to comply with the study procedures and restrictions, including measures to prevent pregnancy and restrictions on sperm donation
排除标准
- •A diagnosis of secondary Sjogren's syndrome according to the revised AECG criteria
- •Severe complications of Sjogren's syndrome
- •Systemic immunosuppressant therapy, cyclophosphamide, or B-cell depleting therapy within 6 months prior to the screening visit
- •Corticosteroid therapy exceeding 7.5 mg prednisone equivalents per day
- •A positive test result for hepatitis B (HBV), hepatitis C (HCV), or human immunodeficiency virus (HIV), or tuberculosis, or any other active viral, fungal, yeast or bacterial infection at screening
- •A history suggesting reduced immune function or any other conditions predisposing participants to serious infection
- •A history of lymphoma, myeloma or monoclonal gammopathy of unknown significance (MGUS), or any other malignancies within the past 5 years
- •A diagnosis of fibromyalgia or significant depression
- •Having any concomitant disease or condition that could interfere with the conduct of the study, or that would pose an unacceptable risk to the individual
- •Participation in an investigational drug or device study within 3 months prior to screening
- •Inability to comply with the study protocol for any other reason
- •Women who are lactating, breastfeeding or planning to nurse
- •Using other prohibited medication (moderate or potent inhibitors of CYP3A4; strong inducers of CYP3A4; strong inhibitors of the transporter P-glycoprotein [P-gp]; sensitive substrates of CYP3A4 with a narrow therapeutic index)
研究组 & 干预措施
Placebo
Matching-placebo capsules will be administered orally, 2 times a day, for up to 12 weeks.
干预措施: Placebo (Drug)
RO5459072
RO5459072 at a dose of 100 milligrams (as capsules) will be administered orally, 2 times a day, for up to 12 weeks.
干预措施: RO5459072 (Drug)
结局指标
主要结局
Percentage of Participants With a Clinically Relevant Decrease in European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI) Score
时间窗: 12 weeks
Percentage of participants with a clinically relevant decrease in European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI) Score is defined as participants with absolute decrease of ≥ 3-points in ESSDAI score. ESSDAI is physician-assessed disease activity index developed by EULAR consortium consisting of 44 items in 12 organ-specific 'domains' (constitutional,lymphadenopathy, articular,muscular,cutaneous,glandular,pulmonary,renal,peripheral nervous system,central nervous system,hematological,biological). Each domain is assessed for activity level (i.e., no, low, moderate, high) and assigned a numerical score based on pre-determined weighting of each individual domain. Overall score is calculated as sum of all individual weighted domain scores (ranges from 0 (best) to 123 (worst activity). A score ≥ 5 is considered moderate or severe disease activity and a clinically relevant change in ESSDAI score is defined as absolute decrease of ≥ 3-points.
次要结局
- Change From Baseline in SF-36 Physical Score at Week 12(Baseline (Week -1), Week 12)
- Change From Baseline in EULAR Sjogren's Syndrome Patient-Reported Index (ESSPRI) Pain Component Score at Week 12(Baseline (Week -1), Week 12)
- Average Concentration (Caverage) of RO5459072(Week 2, Week 6, and Week 12)
- Percentage of Participants With a Clinically Relevant Decrease in EULAR Sjogren's Syndrome Patient-Reported Index (ESSPRI) Score(12 weeks)
- Change From Baseline in ESSDAI Score at Week 12(Baseline (Week -1), Week 12)
- Change From Baseline in Short Form 36 Health Survey (SF-36) Mental Score at Week 12(Baseline (Week -1), Week 12)
- Change From Baseline in ESSPRI Dryness Component Score at Week 12(Baseline (Week -1), Week 12)
- Change From Baseline in ESSPRI Fatigue Component Score at Week 12(Baseline (Week -1), Week 12)
- Change From Baseline in Mechanically Stimulated Salivary Flow Rate at Weeks 2, 6, and 12(Baseline, Week 2, Week 6, and Week 12)
- Change From Baseline in Anti-Sjögren's-Syndrome-Related Antigen A at Weeks 6, and 12(Baseline, Week 6, and Week 12)
- Change From Baseline in Rheumatoid Factor at Weeks 6, and 12(Baseline, Week 6, and Week 12)
- Change From Baseline in ESSPRI Score at Week 12(Baseline (Week -1), Week 12)
- Change From Baseline in Total Immunoglobulin M (IgM) at Weeks 6, and 12(Baseline, Week 6, and Week 12)
- Minimum Concentration (Cmin) of RO5459072(Week 2, Week 6, and Week 12)
- Maximum Concentration (Cmax) of RO5459072(Week 2, Week 6, and Week 12)
- Change From Baseline in Total Immunoglobulin G (IgG) at Weeks 6, and 12(Baseline, Week 6, and Week 12)
- Change From Baseline in Tear Flow Rate at Weeks 2, 6, and 12(Baseline, Week 2, Week 6, and Week 12)
- Change From Baseline in Anti-Sjögren's-Syndrome-Related Antigen B at Weeks 6, and 12(Baseline, Week 6, and Week 12)
- Percentage of Participants With Adverse Events(Baseline up to Week 14)