A Phase 2a, Multicenter, Open-Label Study of RVT-1401 for the Treatment of Patients With Moderate to Severe Active Graves' Ophthalmopathy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 7
- 试验地点
- 4
- 主要终点
- Number of Participants With a Change From Normal Physical Examination Findings at Baseline to Abnormal Physical Examination Findings at the End of the Study
研究概览
简要总结
The purpose of this study was to evaluate safety, tolerability, and pharmacodynamic parameters of RVT-1401 in graves' ophthalmopathy (GO) patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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.
- •Clinical diagnosis of Graves' disease with hyperthyroidism associated with active, moderate to severe GO with a Clinical Activity Score (CAS) ≥ 4 for the most severely affected eye at Screening (on the 7-item scale) and Baseline (on the 10-item scale).
- •Onset of active GO within 9 months of screening.
- •Moderate-to-severe active GO (not sight-threatening but has an appreciable impact on daily life), usually associated with one or more of the following: lid retraction ≥ 2 mm, moderate or severe soft tissue involvement, proptosis ≥ 3 mm above normal for race and gender, and/or inconstant or constant diplopia.
- •Other, more specific inclusion criteria are defined in the protocol
排除标准
- •Use of any steroid (intravenous [IV] or oral) with a cumulative dose equivalent to ≥ 1 g of methylprednisolone for the treatment of GO within 3 weeks prior to Screening.
- •Use of rituximab, tocilizumab, or any monoclonal antibody for immunomodulation within the past 9 months prior to Baseline.
- •Total IgG level < 6g/L at Screening.
- •Absolute neutrophil count <1500 cells/mm3 at Screening.
- •Participants with decreased best corrected visual acuity due to optic neuropathy as defined by a decrease in vision of 2 lines on the Snellen chart, new visual field defect, or color defect secondary to optic nerve involvement within the last 6 months at Screening.
- •Previous orbital irradiation or surgery for GO.
- •Other, more specific exclusion criteria are defined in the protocol
研究组 & 干预措施
RVT-1401
RVT-1401 680 milligrams (mg) weekly for two weeks followed by 340 mg weekly for four weeks, administered subcutaneously
干预措施: RVT-1401 (Drug)
结局指标
主要结局
Number of Participants With a Change From Normal Physical Examination Findings at Baseline to Abnormal Physical Examination Findings at the End of the Study
时间窗: up to Week 18
Abnormality was determined by the investigator.
Number of Participants With Clinically Significant Findings Related to Electrocardiograms (ECGs)
时间窗: up to Week 18
Clinical significance was determined by the investigator.
Percent Change From Baseline in Total Immunoglobulin G (IgG), IgG1, IgG2, IgG3, and IgG4 Levels
时间窗: Baseline; Week 7; Week 6 and 7 combined
The serum levels of total IgG and IgG subclasses (1-4) were determined. Percent change from Baseline was calculated as the mean value at the specified time frame (Week 7, Week 6 and 7 combined) minus the Baseline value, divided by the Baseline value x 100. A negative percent change from Baseline represents clinical improvement.
Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Serious AE (SAE), Treatment-related Adverse Event (AE), and Death During the 6-week Treatment Period
时间窗: from Baseline up to Week 6
AEs were defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs were defined as AEs that either started on or after the date of the first dose of study drug and on or before the date of the last dose of study drug + 42 days, or had no recorded start date and the stop date was in between the date of the first dose and the last dose of study drug + 42 days. 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.
Mean Change From Baseline in Levels of Anti-thyroid-stimulating Hormone Receptor (Anti-TSHR) Antibodies at Week 7
时间窗: Baseline; Week 7
The serum levels of anti-TSHR antibodies were determined. Change from Baseline was calculated as the Week 7 value minus the Baseline value. A negative change from Baseline represents clinical improvement.
Number of Participants With Clinically Significant Findings Related to Vital Signs
时间窗: up to Week 18
Clinical significance was determined by the investigator.
次要结局
- Number of Participants With an Overall Proptosis Response(Up to Week 18)
- 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)
- Mean Change From Baseline in Proptosis in the Study Eye and Non-study Eye at Week 7(Baseline; Week 7)
- 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)
- Serum Concentration at the End of the Dosing Interval (Ctrough) of RVT-1401(Week 2, Week 3, Week 4, Week 5, Week 6 Day 36, and Week 7)
- Number of Participants With Anti-RVT-1401 Antibody and Confirmed Anti-RVT-1401 Antibody at Week 7(Week 7)