A Randomized, Double-blind, Multicenter, Placebo-controlled Phase 3 Study With Open-label Period to Evaluate the Efficacy and Safety of Inebilizumab in Adults With Myasthenia Gravis
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- Amgen
- 入组人数
- 238
- 试验地点
- 104
- 主要终点
- Change From Baseline at Week 26 in Myasthenia Gravis Activities of Daily Living (MG-ADL) Score in the Overall Study Population
研究概览
简要总结
Randomized, double-blind, placebo-controlled, Phase 3, parallel-group study with optional open-label extension.
详细描述
This study is a phase 3, randomized, double-blind, placebo-controlled study, to be conducted at approximately 120 study sites. Approximately 230 participants (188 acetylcholine receptor antibody positive [AChR-Ab+] and 42 muscle-specific tyrosine kinase antibody positive [MuSK-Ab+]) will be enrolled. Participants with Myasthenia Gravis (MG) who are positive for anti-AChR or anti-MuSK antibodies will be enrolled and analyzed. Patients who do not have anti-AChR or anti-MuSK antibodies will not be enrolled. Patients with Myasthenia Gravis Foundation of America (MGFA) classification II, III, or IV disease, Myasthenia Gravis Activities of Daily Living (MG-ADL) score at screening and randomization between 6 and 10 with > 50% of this score attributed to non-ocular items, or an MG-ADL score >=11, Quantitative Myasthenia Gravis (QMG) score >= 11 at the time of screening and randomization, and use of a corticosteroid and/or non-steroidal immunosuppressant will be included in the study.
All subjects who complete the randomized controlled period (RCP) will have the option to enroll in a 3-year (156 weeks) open-label period.
Study acquired from Horizon in 2023.
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
This is a double-blind study in which the IV inebilizumab and the IV placebo are matching in appearance.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of MG with anti-AChR or anti-MuSK antibody.
- •MGFA Clinical Classification Class II, III, or IV.
- •MG-ADL score of 6 or greater at screening and at randomization with > 50% of this score attributed to non-ocular items.
- •QMG score of 11 or greater.
- •Participants must be on:
- •Corticosteroids only, with no dose increase within 4 weeks prior to randomization, or
- •One allowed non-steroidal immunosuppressive therapy (IST), with continuous use for at least 6 months prior to randomization and no dose increase within 4 months prior to randomization, or
- •Combination of (1) corticosteroids with no dose increase within 4 weeks prior to randomization and (2) one allowed non-steroidal IST with continuous use for at least 6 months prior to randomization and no dose increase within 4 months prior to randomization.
- •Allowed ISTs, alone or in combination with corticosteroids, are azathioprine, mycophenolate mofetil, and mycophenolic acid.
排除标准
- •Receipt of the following medications within the 4 weeks prior to Day 1:
- •Cyclosporine (except eye drops)
- •Tacrolimus (except topical)
- •Methotrexate
- •Current use of:
- •Corticosteroids (Prednisone > 40 milligram (mg)/day or > 80 mg over a 2-day period (or equivalent dose of other corticosteroids).
- •Acetylcholinesterase inhibitors (pyridostigmine) > 480 mg/day) or unstable dose in the 2 weeks prior to Day
- •Azathioprine > 3 mg/kilogram (kg)/day
- •Mycophenolate mofetil > 3 grams/day or mycophenolic acid > 1440 mg/day
- •Any IST, alone or in combination with corticosteroids, except for azathioprine, mycophenolate mofetil, and mycophenolic acid.
研究组 & 干预措施
Placebo, (AChR-Ab+) MG
Participants will receive placebo administered IV on Days 1, 15, and 183 of the RCP.
Participants who elect to enter the OLP will receive inebilizumab administered IV on OLP Days 1,15, 183, 365, 547, 729, and 911.
干预措施: IV Placebo (Drug)
Placebo, (MuSK-Ab+) MG
Participants will receive placebo administered IV on Days 1 and 15 of the RCP. Participants who elect to enter the OLP will receive inebilizumab administered IV on OLP Days 1,15, 183, 365, 547, 729, and 911.
干预措施: IV Placebo (Drug)
Inebilizumab, (AChR-Ab+) MG
Participants will receive inebilizumab administered intravenously (IV) on Days 1, 15, and 183 of the RCP.
Participants who elect to enter the open label phase (OLP) will receive inebilizumab administered IV on OLP Days 1, IV placebo on OLP Day 15 (to avoid potential unblinding), and inebilizumab IV on OLP Days 183, 365, 547, 729, and 911.
干预措施: inebilizumab (Drug)
Inebilizumab, (MuSK-Ab+) MG
Participants will receive inebilizumab administered IV on Days 1 and 15 of the RCP.
Participants who elect to enter the OLP will receive inebilizumab administered IV on OLP Day 1, IV placebo on OLP Day 15 (to avoid potential unblinding), and inebilizumab IV on OLP Days 183, 365, 547, 729, and 911.
干预措施: inebilizumab (Drug)
结局指标
主要结局
Change From Baseline at Week 26 in Myasthenia Gravis Activities of Daily Living (MG-ADL) Score in the Overall Study Population
时间窗: Baseline and Week 26
MG-ADL score is an 8-item questionnaire that focuses on relevant symptoms and functional performance of activities of daily living over the previous 7 days. The MG-ADL score assesses 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 response is graded 0 (normal) to 3 (most severe). The range of total MG-ADL scores is 0-24. A higher score represents more severe disease Outcome measure is reported for the overall population.
次要结局
- Change From Baseline in Quantitative Myasthenia Gravis (QMG) Score at Week 26 in the Overall Study Population(Baseline and Week 26)
- Change From Baseline at Week 26 in MG-ADL Score in Anti-AChR-Ab+ and Anti-MuSK-Ab+ Populations(Baseline and Week 26)
- Change From Baseline in QMG Score at Week 26 in Anti-AChR-Ab+ and Anti-MuSK-Ab+ Populations(Baseline and Week 26)
- Percentage of Participants With Both ≥ 3-point Improvement in MG-ADL Score at Week 26 and no Use of Rescue Therapy Between Day 28 and Week 26 in the Overall Study Population(Up to Week 26)
- Percentage of Participants With Both ≥ 3-point Improvement in MG-ADL Score at Week 26 and no Use of Rescue Therapy Between Day 28 and Week 26 in Anti-AChR-Ab+ and Anti-MuSK-Ab+ Populations(Up to Week 26)
- Percentage of Participants With Both ≥ 3-point Improvement in MG-ADL Score at Week 52 and no Use of Rescue Therapy Between Day 28 and Week 52 in Anti-AChR-Ab+ Population(Up to Week 52)
- Percentage of Participants With no Use of Rescue Therapy Between Day 28 and Week 52 in Anti-AChR-Ab+ Population(Up to Week 52)
- Change From Baseline in MG-ADL Score at Week 52 in the Anti-AChR-Ab+ Population(Baseline and Week 52)
- Change From Baseline in QMG Score at Week 52 in the Anti-AChR-Ab+ Population(Baseline and Week 52)
- Change From Baseline in Myasthenia Gravis Composite (MGC) Score at Week 26 in the Overall Study Population(Baseline and Week 26)
- Change From Baseline in MGC Score at Week 26 in Anti-AChR-Ab+ and Anti-MuSK-Ab+ Populations(Baseline and Week 26)
- Change From Baseline in MGC Score at Week 52 in Anti-AChR-Ab+ Population(Baseline and Week 52)
- Change From Baseline in Myasthenia Gravis Quality of Life-15, Revised (MGQOL-15r) Score at Week 26 in the Overall Study Population(Baseline and Week 26)
- Change From Baseline in MGQOL-15r Score at Week 26 in Anti-AChR-Ab+ and Anti-MuSK-Ab+ Populations(Baseline and Week 26)
- Change From Baseline in MGQOL-15r Score at Week 52 in Anti-AChR-Ab+ Population(Baseline and Week 52)
- Percentage of Participants With Patient Global Impression of Change (PGIC) Scores at Week 26 in the Overall Study Population(Week 26)
- Percentage of Participants With PGIC Scores at Week 26 in Anti-AChR-Ab+ and Anti-MuSK-Ab+ Populations(Week 26)
- Percentage of Participants With PGIC Scores at Week 52 in Anti-AChR-Ab+ Population(Week 52)
- Percentage of Participants Experiencing Exacerbation by Week 26 in the Overall Study Population(Up to Week 26)
- Percentage of Participants Experiencing Exacerbation by Week 26 in Anti-AChR-Ab+ and Anti-MuSK-Ab+ Populations(Up to Week 26)
- Percentage of Participants Experiencing Exacerbation by Week 52 in Anti-AChR-Ab+ Population(Up to Week 52)
- Percentage of Participants Achieving Minimal Symptom Expression (MSE) at Week 26(From Day 28 to Week 26)
- Percentage of Participants With Steroid Tapered to ≤ 5 mg/Day Steroid at Week 26 in the Overall Study Population(Week 26)
- Percentage of Participants With Steroid Tapered to ≤ 5 mg/Day Steroid at Week 26 in Anti-AChR-Ab+ and Anti-MuSK-Ab+ Populations(Week 26)
- Percentage of Participants With Steroid Tapered to ≤ 5 mg/Day Steroid at Week 52 in Anti-AChR-Ab+ Population(Week 52)
- Percentage of Participants Who Achieved ≥ 50% Steroid Reduction at Week 26 in the Overall Study Population(Week 26)
- Percentage of Participants Who Achieved ≥ 50% Steroid Reduction at Week 26 in the Anti-AChR-Ab+ and Anti-MuSK-Ab+ Populations(Week 26)
- Percentage of Participants Who Achieved ≥ 50% Steroid Reduction at Week 52 in the Anti-AChR-Ab+ Population(Week 52)
- Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs), AE of Special Interest (AESIs) and Serious TEAEs (SAEs).(For RCP AE reporting: from Day 1 to the end of RCP or cutoff date (up to 65.4 weeks))
- Percentage of Participants With Anti-drug Antibodies (ADA) by Week 26 in the Overall Study Population(From Baseline to Week 26)
- Percentage of Participants With ADA by Week 26 in Anti-AChR-Ab+ and Anti-MuSK-Ab+ Populations(From Baseline to Week 26)
- Percentage of Participants With ADA by Week 52 in Anti-AChR-Ab+ Population(From Baseline to Week 52)
- Time to Maximum Serum Concentration (Tmax) of Inebilizumab in Anti-AChR-Ab+ and Anti-MuSK-Ab+ Populations(Days 1 and 15 for Anti-MuSK-Ab+ population; Days 1, 15 and 183 (Week 26) for Anti-AChR-Ab+ population)
- Maximum Observed Serum Concentration (Cmax) of Inebilizumab in Anti-AChR-Ab+ and Anti-MuSK-Ab+ Populations(Days 1 and 15 for Anti-MuSK-Ab+ population; Days 1, 15 and 183 (Week 26) for Anti-AChR-Ab+ population)
- Area Under the Serum Concentration Time Curve of the Dosing Interval (AUC0-14d) of Inebilizumab(Days 1 and 15 for Anti-MuSK-Ab+ population; Days 1, 15 and 183 (Week 26) for Anti-AChR-Ab+ population)