A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Telitacicept in Adult Participants With Active Primary Sjögren's Disease
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 250
- 试验地点
- 43
- 主要终点
- To evaluate the efficacy of telitacicept versus placebo at Week 48 in the change from baseline in the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score at Week 48.
研究概览
简要总结
Phase 3 Study of Telitacicept in Active Primary Sjögren's Disease (UPSTREAM SjD)
详细描述
Telitacicept (RC18) is a recombinant fusion protein designed to target B-cell-mediated immune pathways. It consists of the extracellular domain of transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) linked to the Fc portion of human immunoglobulin G1 (IgG1).
Telitacicept binds with high affinity to the cytokines B-lymphocyte stimulator (BLyS, also known as BAFF) and A Proliferation-Inducing Ligand (APRIL). By binding these soluble factors, telitacicept prevents their interaction with cell-surface receptors on B cells, including TACI, B-cell maturation antigen (BCMA), and BAFF receptor (BAFF-R).
This inhibition reduces BLyS/APRIL signaling, leading to decreased B-cell survival, reduced differentiation of B cells into immunoglobulin-producing plasma cells, and lowering of autoantibody production, increased BLyS and APRIL levels, B-cell hyperactivity, and autoantibody production are associated with multiple autoimmune diseases.
Modulation of the BLyS/APRIL pathway is intended to reduce pathogenic B-cell activity and downstream immune effects that contribute to disease manifestations in Sjogren's disease and other B-cell-mediated autoimmune conditions.
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)
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
- •Male or female aged 18 to 75 years of age (both inclusive) at screening
- •Participants must meet the 2016 American College of Rheumatology (ACR)/EULAR classification criteria for primary Sjogren's Syndrome at the time of screening.
- •ESSDAI ≥5 at screening (score calculated excluding renal, pulmonary and neurological domains)
- •Participants are seropositive for antibodies to Sjogren's Syndrome A (SSA)/Anti-Sjogren's Syndrome A (Ro) at the Screening Visit.
- •Additional inclusion criteria are defined in the protocol
排除标准
- •Participants who have a systemic autoimmune disease other than Primary Sjogren's Disease, such as rheumatoid arthritis, systemic lupus erythematosus, or systemic sclerosis, that can better explain the majority of the symptoms (i.e., secondary Sjogren's Disease)
- •Participants who have another autoimmune disease or inflammatory condition that could interfere with assessment of response of Primary Sjogren's Disease to therapy (e.g., systemic sclerosis, inflammatory bowel disease, gout).
- •Participants with severe fibromyalgia that could interfere with the assessment of response of Primary Sjogren's Disease to therapy
- •Active life-threatening or organ-threatening complications of Primary Sjogren's Disease at the time of screening based on investigator evaluation
- •Significant, uncontrolled medical disease in any organ system not related to Primary Sjogren's Disease (e.g., poorly controlled asthma, cardiovascular disease, accelerated hypertension, major depression, etc.) that in the opinion of the investigator would preclude participant participation.
- •Additional exclusion criteria are defined in the protocol
研究组 & 干预措施
Placebo
Placebo
干预措施: Placebo (Drug)
Telitacicept
Telitacicept
干预措施: Telitacicept (Biological)
结局指标
主要结局
To evaluate the efficacy of telitacicept versus placebo at Week 48 in the change from baseline in the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score at Week 48.
时间窗: Week 48
Change from baseline in the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score at Week 48.
次要结局
- To evaluate the efficacy of telitacicept versus placebo at Week 48 in the treatment of adult participants with pSD.(Week 48)
- To evaluate the efficacy of telitacicept versus placebo in improving glandular function during the trial.(Week 48)
- To evaluate the effect of telitacicept versus placebo in improving patient-reported outcomes (i.e., how participants feel and function) during the trial.(Week 48)
- To evaluate the efficacy of telitacicept versus placebo at Week 48 in the change from baseline in the physician's global assessment of disease activity (Physician GDA) score at Week 48(Week 48)
- To evaluate the efficacy of telitacicept versus placebo at Week 48 in the change from baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score at Week 48(Week 48)
- To evaluate the efficacy of telitacicept versus placebo at Week 48 in the change from baseline in the participant's global assessment of disease activity (Patient GDA) at Week 48.(Week 48)