A Randomized, Double-blind, Placebo-controlled Phase III Study to Evaluate the Efficacy, Safety, and Tolerability of Remibrutinib in Patients With Generalized Myasthenia Gravis, Followed by an Open-label Extension Phase
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 180
- 试验地点
- 153
- 主要终点
- Change from baseline to Month 6 in Myasthenia Gravis Activity of Daily Living (MG-ADL) total score
研究概览
简要总结
A study to evaluate the efficacy, safety and tolerability of Remibrutinib versus placebo in adult patients with Generalized Myasthenia Gravis who are on stable, standard-of-care (SOC) treatment.
详细描述
This study is a randomized, double-blind, placebo-controlled, multicenter, Phase III study, to evaluate the efficacy, safety and tolerability of remibrutinib in gMG patients who are on stable SOC treatment. Approximately 180 eligible participants will be randomized in a ratio of 1:1, to receive either remibrutinib or matching placebo.
The study consists of a Core Part (6-months double-blind treatment) and an Extension Part (up to 60-month open-label treatment).
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 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients with gMG (age 18-85 years)
- •Confirmed diagnosis of Myasthenia Gravis Foundation of America (MGFA) Class II-IV gMG at screening and likely not in need of a respirator for the duration of the study, as judged by the Investigator
- •Documented evidence of positive serologic testing for AChR+ antibody or MuSK+ antibody at screening, OR seronegative for both AChR and MuSK antibodies at screening
- •Baseline MG-ADL score ≥ 6 with ≥ 50% of the total score due to non ocular symptoms
- •Participants who have been receiving a standard-of-care treatment as specified in the protocol
- •Able to safely swallow the study medication according to investigator clinical judgement based on a bedside swallowing test or another formal swallowing test in line with local practice, both at Screening and Baseline
排除标准
- •Prior to baseline have been treated with intravenous immunoglobulins or plasma exchange (IVIg/PLEX) in the past month, with rituximab in the past 6 months, eculizumab in the past 2 months, ravulizumab or other complement inhibitors in the past 3 months, efgartigimod or other anti-FcRn therapies in the past 3 months, or had a thymectomy in the past 6 months or a planned thymectomy during the trial period
- •Women of child bearing potential, defined as all women physiologically capable of becoming pregnant, from menarche until becoming post-menopausal, unless they are using highly effective methods of contraception during dosing and for 1 week after stopping of study treatment
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Placebo arm
Core Part: Placebo tablet taken orally
[Extension Part: Open-label remibrutinib tablet taken orally]
干预措施: Placebo (Other)
Remibrutinib arm
Core Part: Remibrutinib tablet taken orally
[Extension Part: Open-label remibrutinib tablet taken orally]
干预措施: Remibrutinib (Blinded) (Drug)
Remibrutinib arm
Core Part: Remibrutinib tablet taken orally
[Extension Part: Open-label remibrutinib tablet taken orally]
干预措施: Remibrutinib (Open Label) (Drug)
Placebo arm
Core Part: Placebo tablet taken orally
[Extension Part: Open-label remibrutinib tablet taken orally]
干预措施: Remibrutinib (Open Label) (Drug)
结局指标
主要结局
Change from baseline to Month 6 in Myasthenia Gravis Activity of Daily Living (MG-ADL) total score
时间窗: Baseline to Month 6
The MG-ADL is a categorical scale that assesses MG symptoms and their effects on daily activities. MG-ADL is composed of items related to patient's assessment of functional disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb (2 items) impairment related to effects from MG. Each item is assessed on a 4-points scale where a score 0 represents normal function and a score 3 represents loss of ability to perform that function (total score 0 to 24).
次要结局
- Change from baseline to Month 6 in Quantitative Myasthenia Gravis (QMG) total score(Baseline to Month 6)
- Proportion of participants with ≥ 5 points reduction from baseline to Month 6 of QMG total score without rescue medication and/or strongly confounding prohibited medication(Baseline to Month 6)
- Proportion of participants with ≥ 3 points reduction from baseline to Month 6 of Myasthenia Gravis Activity of Daily Living (MG-ADL) scale total score without rescue medication and/or strongly confounding prohibited medication(Baseline to Month 6)
- Proportion of participants achieving Minimal Symptom Expression (MSE) at Month 6, defined as MG-ADL score of 0 or 1 at Month 6 without rescue therapy and/or strongly confounding prohibited medication(Month 6)
- Change from baseline to Month 6 in Myasthenia Gravis Composite score (MGC) total score(Baseline to Month 6)
- Change from baseline to Month 6 in revised Myasthenia Gravis Quality of Life Questionnaire (MG-QOL15r) survey score(Baseline to Month 6)
- Incidence of adverse events(Month 7 to month 66)
- Proportion of time during which participants showed a reduction of ≥ 2 points in MG-ADL total score, that was maintained up to Month 6(Baseline to Month 6)
- Proportion of early MG-ADL responders during treatment (early responders with first MG-ADL improvement from baseline of ≥ 2 points occurring by week 4）(Baseline to week 4)
- Change from baseline to Month 6 in EuroQol-5 Dimensions-5 Level (EQ-5D-5L)(Baseline to Month 6)
- Proportion of participants achieving a reduction from baseline of ≥ 3 points in MGC total score at Month 6(Baseline to Month 6)
- Change from baseline in MG-ADL total score(Baseline to Month 66)
- Proportion of participants achieving a reduction from core part in oral corticosteroids (OCS) dose till the end of extension part(Baseline to month 66)
- Change from baseline in QMG total score(Baseline to Month 66)
- Change from baseline in MGC total score(Baseline to Month 66)
- Incidence of adverse events(Baseline to Month 6)