A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of lGIV-C as a Corticosteroid Sparing Agent in Corticosteroid Dependent Patients With Generalized Myasthenia Gravis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 39
- 主要终点
- Percent of Subjects Achieving a 50% or Greater Reduction in CS Dose (Prednisone or Equivalent) From Baseline to Week 39
研究概览
简要总结
This is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of Immune Globulin (Human), 10% Caprylate/Chromatography Purified (IGIV-C) as a corticosteroid (CS)-sparing agent in subjects with CS-dependent Myasthenia Gravis (MG).
详细描述
This study consists of 2 phases: IGIV-C Run-in Phase and Corticosteroid Tapering/IGIV-C Maintenance Phase.
In the Run-in Phase, subjects will receive a total of 3 doses of IGIV-C (1 loading dose of 2 g/kg and 2 maintenance doses of 1 g/kg) while maintaining a stable dose of corticosteroids.
In the CS Tapering/IGIV-C Maintenance Phase, subjects will continue 1 g/kg IGIV-C and begin a prescribed CS tapering regimen where the CS dose is decreased every 3 weeks.
Approximately 60 subjects are planned to be enrolled in the study across multiple centers in North America and Europe. The total duration of study participation for each subject is up to 45 weeks.
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 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Anti-acetylcholine receptor antibody positive
- •Confirmed diagnosis of generalized MG historically meeting the clinical criteria for diagnosis of MG defined by the Myasthenia Gravis Foundation of America (MGFA) classification of Class II, III, IV, or V historically
- •At Screening, subjects may have symptoms controlled by CS or were MGFA Class II-IVa inclusive (Class IVb and Class V excluded). Subjects who only have a history of ocular MG may not enroll.
- •On systemic CS for a minimum period of at least 3 months and on a stable CS dose of >=15 mg/day and <=60 mg/day (prednisone equivalent) for the month prior to Screening.
- •Had a tapering CS dose that the study investigator considered to be appropriate.
- •At least 1 previous completed attempt to taper CS in order to minimize CS dose (lowest feasible dose based on observed MG signs and symptoms)
排除标准
- •Any dose change in concomitant immunosuppressant therapy, other than CS, in the prior 6 months
- •Any change in CS dose or acetylcholinesterase inhibitor (e.g., pyridostigmine) dose in the 1 month prior to Screening
- •A 3-point change in Quantitative Myasthenia Gravis score, increased or decreased, between the Screening/Week -3 (Visit 0) and Baseline (Week 0 [Visit 1])
- •Any episode of myasthenic crisis (MC) in the 1 month prior to Screening, or (at any time in the past) MC or hospitalization for MG exacerbation associated with a previous CS taper attempt
- •Evidence of malignancy within the past 5 years (non-melanoma skin cancer, carcinoma in situ of cervix is allowed) or thymoma potentially requiring surgical intervention during the course of the trial (intent to perform thymectomy)
- •Thymectomy within the preceding 6 months prior to Screening
- •Rituximab, belimumab, eculizumab or any monoclonal antibody used for immunomodulation within the past 12 months prior to Screening
- •Have received immune globulin treatment given by IV, subcutaneous, or intramuscular route within the last 3 months prior to Screening
- •Received plasma exchange performed within the last 3 months prior to Screening
- •History of anaphylactic reactions or severe reactions to any blood-derived product
- •History of recent (within the last year) myocardial infarction or stroke
- •Uncontrolled congestive heart failure; embolism; or historically documented (within the last year) electrocardiogram changes indicative of myocardial ischemia or atrial fibrillation
- •Current known hyperviscosity or hypercoagulable state
- •Currently receiving anti-coagulation therapy. Oral anti-platelet agents are allowed (e.g., aspirin, clopidogrel, ticlopidine)
- •Females of child-bearing potential who are pregnant, have a positive serum pregnancy test, breastfeeding, or are unwilling to practice a highly effective method of contraception throughout the study.
- •Renal impairment
- •Aspartate aminotransferase or alanine aminotransferase levels exceeding more than 2.5 times the upper limit of normal for the expected normal range for the testing laboratory.
- •Hemoglobin (Hb) levels <9 g/dL
研究组 & 干预措施
IGIV-C
An IGIV-C loading dose of 2 g/kg and maintenance dose of 1 g/kg will be administered in CS dependent subjects with MG.
干预措施: IGIV-C (Drug)
Placebo
0.9% sodium chloride injection, USP or equivalent
干预措施: Placebo (Drug)
结局指标
主要结局
Percent of Subjects Achieving a 50% or Greater Reduction in CS Dose (Prednisone or Equivalent) From Baseline to Week 39
时间窗: Baseline/Week 0 (Visit 1) and Week 39 (Visit 14).
The average daily CS dose was derived for each subject at each scheduled visit based on the prescribed dose and the time interval taking into account any prescribed dose changes between routinely scheduled visits. Subjects who discontinued the study early with adverse outcomes related to MG were considered as not achieving a 50% or greater reduction. The missing dose reduction at Week 39 was imputed using the worst observation carried forward (WOCF) method. For subjects who did not have CS dose prescribed at Week 39 due to other reasons, the last observation carried forward (LOCF) method was used to impute the prescribed CS dose at Week 39. Baseline was defined as the last non-missing measurement taken prior to first dose of study medication. The percent of subjects achieving ≥50% reduction in CS dose from baseline to Week 39 is presented for each treatment group overall and for the baseline daily prednisone equivalent dose level stratification categories.
次要结局
- Mean Percent Change in Daily CS Dose (Prednisone or Equivalent) From Baseline to Week 39(Baseline/Week 0 (Visit 1) and Week 39 (Visit 14).)
- Median Time to First Episode of MG Worsening(From Baseline/Week 0 (Visit 1) to Week 39 (Visit 14).)