A Phase 2a, Randomized, Placebo Controlled, Proof of Mechanism Study to Evaluate the Safety and Efficacy of AMG 557/MEDI5872 in Subjects With Primary Sjögren's Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 14
- 主要终点
- Change From Baseline in European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI) Score at Day 99
研究概览
简要总结
A Phase 2a study to evaluate the efficacy and safety of AMG 557/MEDI5872 in Primary Sjögren's Syndrome
详细描述
This is a Phase 2a, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the clinical and biologic efficacy, as well as the safety of SC doses of AMG 557/MEDI5872 in adult subjects with Primary Sjögren's Syndrome.
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
- Triple (Participant, Investigator, Outcomes Assessor)
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
- •Age 18 through 75 years at the time of signing the ICF.
- •Fulfill American-European Consensus Group (AECG) criteria for pSS
- •ESSDAI score ≥
- •Positive anti-SS-A and/or anti-SS-B autoantibodies and at least IgG > 13 g/L or RF level > upper limit of normal (ULN) or positive test for cryoglobulins
- •Willingness to undergo protocol-required minor salivary gland biopsies.
- •Negative TB test during screening
- •Immunization up to date as determined by local standard of care.
排除标准
- •Previous treatment with AMG 557/MEDI
- •Evidence of signs or symptoms of a viral, bacterial, or fungal infection within 2 weeks (14 days) prior to randomization (Day 1) according to the assessment of the investigator; any infection requiring IV antibiotic or antiviral treatment within 8 weeks of randomization (Day 1); history of herpes zoster within 3 months prior to randomization (Day 1).
- •Evidence of significant renal insufficiency
- •Positive test at screening for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) antibody.
- •Prior administration of any of the following:
- •Belimumab in the past 6 months prior to randomization (Day 1);
- •Rituximab in the past 12 months or CD19+ B cells < 5/µL if rituximab treatment was more than 12 months prior to randomization (Day 1);
- •Abatacept in the past 6 months prior to randomization (Day 1);
- •Tumor necrosis factor inhibitors (adalimumab, certolizumab, etanercept, golimumab, infliximab) in the past 3 months prior to randomization (Day 1);
- •Tocilizumab in the past 3 months prior to randomization (Day 1);
- •Cyclophosphamide (or any other alkylating agent) in the past 6 months prior to randomization (Day 1); cyclosporine (except for eye drops), tacrolimus, sirolimus, mycophenolate mofetil, azathioprine, or leflunomide in the past 3 months prior to randomization (Day 1).
- •Receiving any of the following:
- •Corticosteroids: > 10 mg/day oral prednisone (or equivalent); Any change or initiation of new dose within 4 weeks prior to signing the ICF through randomization (Day 1); Intramuscular, IV, or intra-articular corticosteroids within 4 weeks prior to signing the ICF through randomization (Day 1); Any change or initiation of new dose of topical corticosteroids within 2 weeks prior to signing the ICF through randomization (Day 1);
- •Antimalarials: any increase or initiation of new dose of antimalarials (eg, chloroquine, hydroxychloroquine, quinacrine) within 12 weeks prior to signing the ICF through randomization (Day 1).
- •Methotrexate: > 20 mg/week methotrexate; Any change or initiation of new dose of methotrexate within 4 weeks prior to signing the ICF through randomization (Day 1); Any change in route of administration.
- •Any increase or initiation of new dose of regularly scheduled nonsteroidal anti inflammatory drugs (NSAIDs) within 2 weeks prior to signing the ICF through randomization (Day 1).
- •Cevimeline or pilocarpine and cyclosporine eye drops (Restasis): any increase or initiation of new doses within 2 weeks prior to signing the ICF through randomization (Day 1).
研究组 & 干预措施
MEDI5872 210 mg
Participants will receive a fixed SC dose of 210 mg MEDI5872 every week (QW) from Days 1 to 15 and then every 2 weeks (Q2W) from Days 29 to 85 in double-blind period. In open-label period, participants will continue dosing of MEDI5872 210mg Q2W from Days 99 to 183 and will receive an additional dose of blinded placebo on Day 106.
干预措施: AMG 557/MEDI5872 (Biological)
Placebo/MEDI5872 210 mg
Participants will receive a SC dose of placebo matching with MEDI5872 QW on Days 1, 8, and 15 and then Q2W from Days 29 to 85 in double-blind period. In open-label period, participants will receive a fixed SC dose of 210 mg MEDI5872 QW (Days 99 to 113) and Q2W (Days 127 to 183) in open-label period.
干预措施: Placebo (Other)
结局指标
主要结局
Change From Baseline in European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI) Score at Day 99
时间窗: Baseline (Day 1 predose) and Day 99
The European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI) is a clinical index that measures Sjogren's syndrome disease activity. A physician scores the disease activity level of 12 organ-specific domains (constitutional, lymphadenopathy, articular, muscular, cutaneous, glandular, pulmonary, renal, peripheral nervous system, central nervous system, hematological, and biological). Each domain is assessed for activity level in 3 or 4 levels (i.e., no, low, moderate, high) according to their severity (no disease activity equals to 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. Overall score is calculated as sum of all individual weighted domain scores (ranges from 0 (best) to 123 (worst activity). A higher score indicates worsening of the disease. Adjusted mean change and standard error are presented.
次要结局
- Ratio to Baseline in Peripheral Blood Biomarkers at Day 99(Baseline (Day 1 predose) and Day 99)
- Ratio to Baseline in Minor Salivary Gland Tissue Biomarkers at Day 99(Baseline (Day 1 predose) and Day 99)
- Ratio to Baseline in Focus Score at Day 99(Baseline (Day 1 predose) and Day 99)
- Change From Baseline in European League Against Rheumatism Sjogren's Syndrome Patient Reported Index (ESSPRI) Score at Day 99(Baseline (Day 1 predose) and Day 99)
- Percentage of ESSDAI Responders at Day 99(Baseline (Day 1 predose) and Day 99)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)(Placebo arm: Day 1 (postdose) through Day 99 (predose); Any MEDI5872 210 mg arm: Day 1 (postdose) through Day 296 for MEDI5872 210 mg arm, and Day 99 (postdose) through Day 296 for participants who received placebo at double-blind period)
- Number of Participants With Adverse Events of Special Interest (AESIs)(Placebo arm: Day 1 (postdose) through Day 99 (predose); Any MEDI5872 210 mg arm: Day 1 (postdose) through Day 296 for MEDI5872 210 mg arm, and Day 99 (postdose) through Day 296 for participants who received placebo at double-blind period)