A Phase 2a, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study With an Open-Label Extension of RVT-1401 in Myasthenia Gravis Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 20
- 主要终点
- Open-label Extension Period: Number of Participants With Clinically Significant Changes in Vital Signs
研究概览
简要总结
The purpose of the current study is to assess safety/tolerability and key pharmacodynamic (PD) effects that are considered to be associated with clinical benefit (reduction of total IgG and anti-AChR-IgG) in Myasthenia Gravis patients following treatment with RVT-1401 (also known as IMVT-1401) compared to placebo.
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
Blinded
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
- •Male or female ≥ 18 years of age.
- •Myasthenia Gravis Foundation of America (MGFA) Class II-IVa and likely not in need of a respirator for the duration of the study as judged by the Investigator.
- •QMG score ≥12 at Screening and Baseline.
- •Other, more specific inclusion criteria are defined in the protocol.
排除标准
- •Use of rituximab, belimumab, eculizumab or any monoclonal antibody for immunomodulation within 6 months prior to first dosing.
- •Immunoglobulins given by SC, IV (IVIG), or intramuscular route, or plasmapheresis/plasma exchange (PE) within 4 weeks before Screening.
- •Thymectomy performed < 12 months prior to screening.
- •Total IgG level <6 g/L (at screening).
- •Absolute neutrophil count <1500 cells/mm3(at screening).
- •Other, more specific exclusion criteria are defined in the protocol
研究组 & 干预措施
Regimen A
RVT-1401 680 mg weekly for 6 weeks + optional open-label extension (RVT-1401, 340 mg every 2 weeks for 6 weeks)
干预措施: RVT-1401 (Drug)
Regimen B
RVT-1401 340 mg weekly for 6 weeks + optional open-label extension (RVT-1401, 340 mg every 2 weeks for 6 weeks)
干预措施: RVT-1401 (Drug)
Placebo
Placebo for 6 weeks + optional open-label extension (RVT-1401, 340 mg every 2 weeks for 6 weeks)
干预措施: RVT-1401 (Drug)
Placebo
Placebo for 6 weeks + optional open-label extension (RVT-1401, 340 mg every 2 weeks for 6 weeks)
干预措施: Placebo (Drug)
结局指标
主要结局
Open-label Extension Period: Number of Participants With Clinically Significant Changes in Vital Signs
时间窗: Up to Week 18
Vital signs including SBP, DBP, pulse rate and temperature were measured after resting for at least 5 minutes in a semi-supine position.
Double-blind Treatment Period: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters
时间窗: Up to Week 7
Clinical laboratory parameters included clinical chemistry, hematology and urinalysis.
Double-Blind Treatment Period: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Up to Week 18
An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. SAEs were defined as any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event that may have jeopardized the participant or may have required medical or surgical intervention to prevent one of the other outcomes listed in the definition.
Double-Blind Treatment Period: Number of Participants With Clinically Significant Changes in Vital Signs
时间窗: Up to Week 7
Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate and temperature were measured after resting for at least 5 minutes in a semi-supine position.
Double-blind Treatment Period: Percent Change From Baseline in Levels of Total Immunoglobulin G (IgG)
时间窗: Baseline (Day 1) and Up to Week 7
Serum samples were collected for the analysis of total immunoglobulin G. Percent change from Baseline was calculated as the mean value at the specified time frame (Week 7) minus the Baseline value, divided by the Baseline value x 100.
Open-Label Extension Period: Number of Participants Reporting AEs and SAEs
时间窗: Up to Week 18
An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration. SAEs were defined as any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event that may have jeopardized the participant or may have required medical or surgical intervention to prevent one of the other outcomes listed in the definition.
Double-Blind Treatment Period: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG)
时间窗: Up to Week 7
Twelve-lead ECG was performed after 5 minutes of rest in the supine position.
Double-blind Treatment Period: Percent Change From Baseline in IgG Subclasses 1, 2, 3 and 4
时间窗: Baseline (Day 1) and Up to Week 7
Serum samples were collected for the analysis of IgG 1, 2, 3 and 4 levels. Percent change from Baseline was calculated as the mean value at the specified time frame (Week 7) minus the Baseline value, divided by the Baseline value x 100.
Open-label Extension Period: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters
时间窗: Up to Week 18
Clinical laboratory parameters included clinical chemistry, hematology and urinalysis.
Open-label Extension Period: Number of Participants With Clinically Significant Changes in ECG
时间窗: Up to Week 18
Twelve-lead ECG was performed after 5 minutes of rest in the supine position.
Double-Blind Treatment Period: Percent Change From Baseline in Anti-acetylcholine Receptor Immunoglobulin G (Anti-AChR-IgG) at Week 7
时间窗: Baseline (Day 1) and Week 7
Serum samples were collected for the analysis of Anti-AChR-IgG. Percent change from Baseline was calculated as the mean value at the specified time frame (Week 7) minus the Baseline value, divided by the Baseline value x 100.
次要结局
- Open-label Extension Period: Cmax of RVT-1401(Pre-dose; Day 1, Day 3, Day 5, Day 8, Day 15, Day 22, Day 29, Day 36, Day 38, Day 40, Week 7, Week 8, Week 9, Week 12 and Week 14)
- Open-label Extension Period: Ctrough of RVT-1401(Pre-dose)
- Double-Blind Treatment Period: Maximum Concentration (Cmax) of RVT-1401(Pre-dose; Day 1, Day 3, Day 5, Day 8, Day 15, Day 22, Day 29, Day 36, Day 38, Day 40, Week 7, Week 8)
- Double-Blind Treatment Period: Trough Concentrations (Ctrough) of RVT-1401(Pre-dose)
- Double-Blind Treatment Period: Percentage of Participants With an Improvement/ Response on the QMG Score From Baseline(Baseline (Day 1) to Week 7)
- Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Composite Score (MGC) Score(Baseline (Day 1) and at Week 2, Week 3, Week 4, Week 5, Week 6 (Day 36), Week 7)
- Double-Blind Treatment Period: Area Under the Concentration-time Curve From Time 0 to 168 Hours (AUC0-168h) of RVT-1401(Pre-dose; Day 1, Day 3, Day 5, Day 8, Day 15, Day 22, Day 29, Day 36, Day 38, Day 40, Week 7, Week 8)
- Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Quality of Life 15 Revised Score (MG-QOL 15r) Score(Baseline (Day 1) and at Week 4 and Week 7)
- Double-Blind Treatment Period: Number of Participants Reporting Confirmed Positive Anti-RVT-1401 Antibodies(Up to Week 7)
- Open-Label Extension Period: Number of Participants Reporting Confirmed Positive Anti-RVT-1401 Antibodies(Up to Week 18)
- Open-label Extension Period: AUC0-168h of RVT-1401(Pre-dose; Day 1, Day 3, Day 5, Day 8, Day 15, Day 22, Day 29, Day 36, Day 38, Day 40, Week 7, Week 8, Week 9, Week 12 and Week 14)
- Double-blind Treatment Period: Change From Baseline in the Quantitative Myasthenia Gravis Score (QMG) Score(Baseline (Day 1) and at Week 2, Week 3, Week 4, Week 5, Week 6 (Day 36) and Week 7)
- Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) Score(Baseline (Day 1) and at Week 2, Week 3, Week 4, Week 5, Week 6 (Day 36), Week 7)
- Double-Blind Treatment Period: Percentage of Participants With an Improvement/ Response on the MG-ADL Score(Baseline (Day 1) to Week 7)
- Double-Blind Treatment Period: Percentage of Participants With an Improvement on the MGC Score(Baseline (Day 1) to Week 7)