A Phase IIIb Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 363
- 试验地点
- 65
- 主要终点
- 1. Time to onset of composite 12-week CDP defined as the time from randomization to the first occurrence of either 12-week CDP in 9-HPT, or 12-week CDP in EDSS
研究概览
简要总结
To evaluate the efficacy of ocrelizumab compared with placebo-in all randomized patients and in patients with MRI activity (MRI activity is defined as presence of T1 Gd+ lesion[s] and/or new and/or enlarging T2 lesion[s] as detected by MRI scans during the screening phase) on the basis of the following endpoint:Time to onset of composite 12-week CDP defined as the time from randomization to the first occurrence of at least one of the following progression events: 12-week CDP in 9-HPT, defined as a 20% worsening from baseline in 9-HPT confirmed for at least 12 weeks 12-week CDP in EDSS score, defined as an increase of ≥ 1.0 point from baseline EDSS score in patients with a baseline EDSS score ≤ 5.5 or an increase of ≥0.5 point in patients with a baseline EDSS score of > 5.5 that is confirmed for at least 12 weeks
研究设计
- 分配方式
- Not Applicable
- 主要目的
- B-cell Monitoring Phase
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 64 years（18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Diagnosis of PPMS in accordance with the McDonald criteria (Thompson et al. 2017)
- •EDSS score at screening and baseline ≥ 3.0 to 8.0, inclusive
- •Disease duration from the onset of multiple sclerosis (MS) symptoms relative to randomization date: o Less than 20 years in patients with an EDSS score at screening 7.0-8.0 o Less than 15 years in patients with an EDSS at screening 5.5-6.5 o Less than 10 years in patients with an EDSS at screening ≤ 5.0
- •Documented history or presence at screening of at least one of the following laboratory findings in a cerebrospinal fluid specimen o Elevated IgG index o One or more IgG oligoclonal bands detected by isoelectric focusing
- •Screening and baseline 9-HPT completed in > 25 seconds (average of the two hands)
- •Neurological stability for ≥ 30 days prior to baseline
排除标准
- •History of relapsing-remitting or secondary progressive MS at screening
- •Confirmed serious opportunistic infection
- •Patients who have or have had confirmed or a high degree of suspicion of progressive multifocal leukoencephalopathy
- •Known active malignancy or are being actively monitored for recurrence of malignancy
- •Immunocompromised state defined as one or more of the following: CD4 count < 250/μL, absolute neutrophil count <1.5 x 103/μL, Serum IgG < 4.6 g/L
- •Receipt of a live-attenuated vaccine within 6 weeks prior to randomization
结局指标
主要结局
1. Time to onset of composite 12-week CDP defined as the time from randomization to the first occurrence of either 12-week CDP in 9-HPT, or 12-week CDP in EDSS
1. Time to onset of composite 12-week CDP defined as the time from randomization to the first occurrence of either 12-week CDP in 9-HPT, or 12-week CDP in EDSS
次要结局
- 1. Time to 12-week CDP in EDSS, as a pre-defined increase in EDSS score confirmed for at least 12 weeks
- 2. Time to 24-week CDP in 9-HPT
- 3. Time to 24-week CDP in EDSS, as a pre-defined increase in EDSS score confirmed for at least 24 weeks
- 4. Annual rate of percent change from baseline in total volume of T2 lesions
- 5. Annual rate of percent change from Week 24 in total brain volume
- 6. Incidence and nature of adverse events, serious adverse events, adverse events leading to study treatment withdrawal
- 7. Change from baseline in laboratory test results for hematology and chemistry association of decrease in certain laboratory parameters, and serious infections
- 8. Presence of ADA during the study relative to baseline
- 9. Total plasma clearances (CL) of ocrelizumab
- 10. Volumes of distribution(Vd) of ocrelizumab
- 11. Area under the concentration-time curve (AUC) of ocrelizumab
研究者
Trial Information System - TISL
Scientific
F. Hoffmann-La Roche AG