A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study With an Open-label Extension Period to Evaluate the Efficacy and Safety of Telitacicept in Patients With Generalized Myasthenia Gravis
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 180
- 试验地点
- 165
- 主要终点
- Change from baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) score at Week 24
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of telitacicept in the treatment of generalized myasthenia gravis.
详细描述
Myasthenia gravis (MG) is an autoimmune disease in which autoantibodies disrupt the postsynaptic membrane, impairing nerve-to-muscle signal transmission. The predominant manifestation is muscle weakness, which typically worsens with repeated muscle exertion, such that function is usually the best in the morning with more pronounced weakness at the end of the day. A major challenge in MG is the lack of therapies that effectively treat the disease.
Telitacicept is a fully human TACI-Fc fusion protein that targets B-lymphocyte stimulator (BLyS) and A proliferating-inducing ligand (APRIL), neutralizing their interactions with receptors on B cells. The blockage of BLyS and APRIL interaction with their respective cell membrane receptors (transmembrane activator and CAML interactor [TACI], B-cell maturation antigen, and BLyS receptors) by telitacicept can inhibit B-cell proliferation and maturation. This suppression at the proximal portion of the immune response could alleviate autoimmune symptoms.
This is a randomized, double-blind, placebo-controlled Phase 3 study with an open-label extension (OLE) to evaluate the efficacy and safety of telitacicept in a global patient population with gMG. The total duration of the study is variable but will include an approximately 4-week screening period, a 24-week double-blind treatment period (Week 0 through Week 24), a 48-week OLE (Week 24 through Week 72), followed by an extended OLE period (E-OLE), and an 8-week end-of-study follow-up period. The E-OLE is variable duration, defined as the period after the 48-week OLE period until telitacicept is approved for MG in the country or the further development in the indication is concluded.
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 65+ years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patient aged ≥18 years at screening.
- •Patients have prior confirmed diagnosis of gMG with generalized muscle weakness (typical pattern of weakness meeting the clinical criteria for diagnosis of MG as defined by the Myasthenia Gravis Foundation of America (MGFA) clinical classification II-IV.
- •Patients have positive antibodies against AChR or MuSK at screening.
- •MG-ADL score ≥6 points at screening and baseline with ocular-related score <50% of the total score.
- •QMG score ≥8 points, and ≥ 4 items score at least 2 points at screening and baseline.
排除标准
- •Patients have been diagnosed with any other autoimmune disease which can potentially pose a safety or efficacy confounding risk.
- •Patients having acute or chronic infection.
- •Patients having thymoma within 5 years or received thymectomy ≤6 months prior to screening. Patients with thymoma diagnosed 3-5 years prior to screening may be eligible if thymoma was at a localized stage and definitively treated with complete surgical resection.
- •Patients having current or history of primary immunodeficiency.
- •Patients having history of malignancy within the last 5 years.
- •Patient having prior or continuing diagnosis of serious cardiovascular, liver, kidney, respiratory system, endocrine or hematologic disease.
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
Change from baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) score at Week 24
时间窗: Week 24
The MG-ADL is an 8-item patient-reported outcome measure assessing MG symptoms and their effects on daily activities. Each item in the scale is scored on a 0 to 3 (0=normal, 3=severe disease) point scale. The total score is the sum of all individual item scores ranging from 0 to 24. Higher scores indicate more severe disability due to MG. A decrease from Baseline score indicates improvement.
次要结局
- Change from baseline in Quantitative Myasthenia Gravis (QMG) score at Week 24(Week 24)
- Change from baseline in MG Quality of Life scale (MG-QOL15r) at Week 24(Week 24)
- Proportion of patients with a decrease of ≥2 points from baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) score at Week 24(Week 24)
- Proportion of patients with a decrease of ≥3 points from baseline in Quantitative Myasthenia Gravis (QMG) score at Week 24(Week 24)
- Proportion of patients who achieved minimal symptomatic expression (MSE, defined as having MG-ADL score of 0 or 1) at Week 24(Week 24)
研究者
RemeGen clinical trial information desk
Scientific
Remegen Co. Ltd.