NCT03905525已完成2 期
A 48-week, 6-arm, Randomized, Double-blind, Placebo-controlled Multicenter Trial to Assess the Safety and Efficacy of Multiple CFZ533 Doses Administered Subcutaneously in Two Distinct Populations of Patients With Sjogren's Syndrome (TWINSS)
适应症
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 273
- 试验地点
- 72
- 主要终点
- Change in EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) score from baseline at 24 weeks as compared to placebo
研究概览
简要总结
This study was to evaluate the safety, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of multiple doses of CFZ533 (iscalimab) in patients with Sjögren's Syndrome (SjS).
详细描述
This study consisted of a 6-week screening, 2 treatment periods of 24 weeks each, and a follow-up period of 12 weeks. In Periods 1 and 2, thirteen (13) treatment administration visits were planned, including a weekly loading regimen (2 visits) at the start of each treatment period. One administration equaled to two subcutaneous (s.c.) injections.
This study included two distinct cohorts termed Cohort 1 and Cohort 2.
- Cohort 1: subjects with moderate-to-severe systemic and symptomatic disease involvement.
- Cohort 2: subjects with low systemic disease involvement but high symptom burden.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Patients, investigator staff, persons performing the assessments, were blinded to the identity of the treatment within each cohort from the time of randomization until end of the study visit (week 60)
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Both cohorts must have met all the following criteria:
- •Signed informed consent must be obtained prior to participation in the study
- •Male or female patient >= 18 years of age
- •Classification of Sjögren's Syndrome according to ACR/EULAR 2016 criteria (Shiboski et al 2016)
- •Seropositive for anti-Ro/SSA antibodies
- •Stimulated whole salivary flow rate of >= 0.1 mL/min
- •Able to communicate well with the Investigator to understand and comply with the requirements of the study
- •Inclusion criteria specific for Cohort 1:
- •Screening ESSDAI value >= 5 within the following 8 organ domains: constitutional, lymphadenopathy, glandular, articular, cutaneous, renal, hematologic and biologic
- •Patients with involvement of one or more of the remaining 4 domains are eligible but scores of these domains will not contribute to the assessment for eligibility for Cohort 1
- •At selected sites participating in Cohort 2, patients who based on the above criterion 7, do not qualify for Cohort 1, should be further evaluated for Cohort 2
- •Screening ESSPRI score of >= 5
- •Inclusion criteria specific for Cohort 2:
- •Screening ESSDAI value < 5 within 8 domains scored for inclusion criterion #7 Cohort 1
- •Screening ESSPRI fatigue subscore >= 5 or ESSPRI dryness subscore >= 5
- •Hypergammaglobulinemia defined by IgG greater than upper limit of normal (ULN) or lymphocytopenia (less than lower limit of normal (LLN)) or hypocomplementemia (low C3, or low C4 - when considered due to disease activity and not due to genetic factors)
- •Score of >= 30 on IDEEL symptom bother questionnaire at Screening
排除标准
- •Sjögren's Syndrome overlap syndromes where another autoimmune rheumatic disease constitutes the principal illness
- •Use of other investigational drugs within 5 half-lives of enrollment or within 30 days whichever is longer, or longer if required by local regulations
- •Prior treatment with any of the following within 6 months prior to randomization:
- •B-cell depletors (e.g. rituximab, ianalumab) unless CD19+ B cell count have returned to ≥ 50 cells/µL
- •abatacept
- •anti-tumor necrosis factor alpha monoclonal anti-body
- •intravenous/subcutaneous Ig; plasmapheresis; i.v. or oral cyclophosphamide
- •i.v. or oral cyclosporine A
- •any other immunosuppressants unless explicitly allowed in criterion #5
- •Use of steroids (predniso(lo)ne or equivalent corticosteroid) at dose > 10 mg/day
- •Use of steroids and synthetic DMARDS at inconsistent dose and within 3 months prior to randomization
结局指标
主要结局
Change in EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) score from baseline at 24 weeks as compared to placebo
时间窗: 24 weeks
Cohort 1 - Efficacy
Change in EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) score from baseline at 24 weeks as compared to placebo.
时间窗: 24 weeks
Cohort 2 - Efficacy
次要结局
- Change from baseline in ESSPRI at Week 24(24 weeks)
- Change from baseline in score of Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) questionnaire at Week 24(24 weeks)
- Percent change from baseline in plasma CXCL-13 levels at analysis visits up to end of study(60 weeks)
- Change from baseline in Physician Global Assessment (PhGA) at Week 24(24 weeks)
- Change from baseline in ESSDAI at Week 24(24 weeks)
- Proportion of subjects with at least 12 points improvement measured by score of Impact of Dry Eye on Everyday Life (IDEEL) questionnaire symptom bother module at Week 24.(24 weeks)
- Incidence of adverse events (AEs), serious adverse events (SAEs) from baseline to Week 24 and from week 24 to the end of study(60 weeks)
- Serum Free Light Chain (FLC) levels at analysis visit up to end of study(60 weeks)
- Immunoglobulin IgG and IgM levels at analysis visits up to end of study(60 weeks)
研究者
研究点 (72)
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