An Open-Label, Single-Arm Study to Evaluate the Effectiveness and Safety of Ocrelizumab in Patients With Early Stage Relapsing Remitting Multiple Sclerosis
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 1,225
- 试验地点
- 193
- 主要终点
- Mean Change From Baseline in EDSS Score at Week 96
研究概览
简要总结
This is a prospective, multicenter, open-label, single-arm, phase 3b study which evaluates effectiveness and safety of ocrelizumab in participants with early stage RRMS. The study will consist of an open-label treatment period of 192 weeks and follow-up period of at least 48 weeks.
The optional shorter infusion substudy will evaluate the safety of a shorter infusion of ocrelizumab in a subgroup of participants with early stage RRMS enrolled in the main MA30143 study. Approximately 700 patients will be enrolled in the substudy, and will receive additional 600 mg ocrelizumab administered in a shorter time frame.
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 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have a definite diagnosis of RRMS, as per the revised McDonald 2010 criteria
- •Have a length of disease duration, from first documented clinical attack consistent with MS disease of less than or equal to (</=) 3 years
- •Within the last 12 months one or more clinically reported relapse(s) or one or more signs of MRI activity
- •EDSS of 0.0 to 3.5 inclusive, at screening
- •An agreement to use an acceptable birth control method for women of childbearing potential, during the treatment period and for at least 6 months or longer after the last dose of study drug
排除标准
- •Secondary progressive multiple sclerosis or history of primary progressive or progressive relapsing MS
- •Inability to complete an MRI
- •Known presence of other neurological disorders
- •Exclusions Related to General Health:
- •Pregnancy or lactation
- •Participants intending to become pregnant during the study or within 6 months after the last dose of the study drug
- •Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
- •History or currently active primary or secondary immunodeficiency
- •Lack of peripheral venous access
- •History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
- •Significant or uncontrolled somatic disease or any other significant disease that may preclude participant from participating in the study
- •Congestive heart failure (New York Heart Association III or IV functional severity)
- •Known active bacterial, viral, fungal, mycobacterial infection or other infection, (excluding fungal infection of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks prior to screening or oral antibiotics 2 weeks prior to screening
- •History of malignancy, major opportunistic infections, alcohol or drug abuse, recurrent or chronic infection, and/or coagulation disorders
- •Exclusions Related to Medications:
- •Received any prior approved disease modifying treatment (DMT) with a label for MS, for example, interferons, glatiramer acetate, natalizumab, alemtuzumab, daclizumab, fingolimod, teiflunomide and dimethylfumarate
- •Receipt of a live vaccine or attenuated live vaccine within 6 weeks prior to the baseline visit
- •Previous treatment with B-cell targeted therapies (i.e., rituximab, ocrelizumab, atacicept, belimumab, or ofatumumab)
- •Any previous treatment with immunosuppressants/ immunomodulators/ antineoplastic therapies (cyclophosphamide, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, cladribine, mitoxantrone, laquinimod, total body irradiation, or bone marrow transplantation)
- •Treatment with investigational DMT
- •Treatment with fampridine/dalfamipridine unless on stable dose for >/=30 days prior to screening
- •Exclusion related to Shorter Infusion Substudy:
- •Any previous serious IRRs experienced with ocrelizumab treatment
研究组 & 干预措施
Ocrelizumab
Ocrelizumab will be administered intravenously (IV) as two 300-milligram (mg) infusions (infusion length=2.5 hours) on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period.
干预措施: Ocrelizumab (Drug)
Substudy Group 1
At week 24 of the main study, eligible participants will be randomized to receive 600 mg ocrelizumab infused over approximately 3.5 hours every 24 weeks for the remainder of the study duration
干预措施: Ocrelizumab (Drug)
Substudy Group 2
At week 24 of the main study, eligible participants will be randomized to receive 600 mg ocrelizumab infused over approximately 2 hours followed by sodium chloride given as a slow infusion over the remaining 1.5 hours to mimic the standard-length infusion (3.5 hour) every 24 weeks for the remainder of the study duration
干预措施: Ocrelizumab (Drug)
结局指标
主要结局
Mean Change From Baseline in EDSS Score at Week 96
时间窗: Baseline, Week 96
Mean Change From Baseline in EDSS Score at Week 120
时间窗: Baseline, Week 120
Mean Change From Baseline in EDSS Score at Week 144
时间窗: Baseline, Week 144
Percentage of Participants Without Relapse
时间窗: Baseline up to 4 years
Relapse is defined as occurrence of new or worsening neurological symptoms attributable to MS, as determined using EDSS/FSS assessment.
Annualized Relapse Rate
时间窗: Baseline up to 4 years
Relapse is defined as occurrence of new or worsening neurological symptoms attributable to MS, as determined using EDSS/FSS assessment. The adjusted annualized relapse rate is reported which is: Adjusted by age at disease diagnosis, Baseline EDSS, Presence of T1 Gd-enhanced lesion at screening and Presence of relapses in the last year prior to enrollment. Log-transformed exposure time is included as an offset variable. The report contains data up to week 192 of the treatment period of each individual participant.
Mean Change From Baseline in EDSS Score at Week 168
时间窗: Baseline, Week 168
Mean Change From Baseline in EDSS Score at Week 192
时间窗: Baseline, Week 192
Sub Study: Number of Participants With IRRs Occurring During or Within 24 Hours Following the First Infusion After Randomization to the Shorter Infusion Substudy
时间窗: Week 24 through Week 144
Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 24 Weeks and 48 Weeks as Measured Using Expanded Disability Status Scale (EDSS)
时间窗: Baseline up to 4 years
The EDSS-Expanded Disability Status Scale is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death). Disability progression as measured by EDSS is defined as ≥1 point increase in EDSS score from a baseline EDSS score of 1-5 inclusive, a 0.5-increase from a baseline EDSS score higher than 5 and a 1.5-increase from a baseline EDSS score from 0 to 1 exclusive. Disability progression was considered confirmed if a sustained change in EDSS for a minimum of 24 weeks (-2 weeks) from the initial progression event was seen i.e. the change in EDSS must have been sustained at all available visits for a minimum of 24 weeks/48 weeks.
Percentage of Participants With 24-Week and 48-Week Confirmed Disability Improvement (CDI) During the Year 1 Treatment Period, as Measured Using EDSS
时间窗: At Weeks 24 and 48 during Year 1
CDI is defined as an improvement of ≥1 point on the EDSS score confirmed at a regular scheduled visit at least 24/48 weeks after the initial documentation of neurological worsening (measured only participants with a baseline EDSS of ≥2.0). EDSS is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death).
Percentage of Participants Event-Free for CDP Sustained for at Least 24 and 48 Weeks at Year 1, as Measured Using EDSS
时间窗: Year 1 (Weeks 24 and 48)
The EDSS-Expanded Disability Status Scale is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death). Disability progression as measured by EDSS is defined as ≥1 point increase in EDSS score from a baseline EDSS score of 1-5 inclusive, a 0.5-increase from a baseline EDSS score higher than 5 and a 1.5-increase from a baseline EDSS score from 0 to 1 exclusive. Disability progression was considered confirmed if a sustained change in EDSS for a minimum of 24 weeks (-2 weeks) from the initial progression event was seen i.e. the change in EDSS must have been sustained at all available visits (during Year 1) for a minimum of 24 weeks/48 weeks. Percentage of participants who did not have CPD sustained for 24 and 48 weeks are reported here.
Percentage of Participants With 24-Week and 48-Week CDI During the Year 2 Treatment Period, as Measured Using EDSS
时间窗: At Weeks 48, 72 and 96 during Year 2
CDI is defined as an improvement of 1 point on the EDSS score confirmed at a regular scheduled visit at least 24/48 weeks after the initial documentation of neurological worsening (measured only participants with a baseline EDSS of ≥2.0). EDSS is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death).
Percentage of Participants Event-free for CDP Sustained for at Least 24 and 48 Weeks at Year 2, as Measured Using EDSS
时间窗: Year 2 (Weeks 72 and 96)
The EDSS-Expanded Disability Status Scale is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death). Disability progression as measured by EDSS is defined as ≥1 point increase in EDSS score from a baseline EDSS score of 1-5 inclusive, a 0.5-increase from a baseline EDSS score higher than 5 and a 1.5-increase from a baseline EDSS score from 0 to 1 exclusive. Disability progression was considered confirmed if a sustained change in EDSS for a minimum of 24 weeks (-2 weeks) from the initial progression event was seen i.e. the change in EDSS must have been sustained at all available visits (during Year 1) for a minimum of 24 weeks/48 weeks. Percentage of participants who did not have CPD sustained for 24 and 48 weeks are reported here.
Percentage of Participants With 24-Week and 48-Week CDI at Year 4, as Measured Using EDSS
时间窗: At Weeks 144, 168 and 192 during Year 4
CDI is defined as an improvement of 1 point on the EDSS score confirmed at a regular scheduled visit at least 24 weeks after the initial documentation of neurological worsening (measured only participants with a baseline EDSS of ≥2.0). EDSS is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death).
Percentage of Participants Event-free for CDP Sustained for at Least 24 and 48 Weeks at Year 4, as Measured Using EDSS
时间窗: Year 4 (Weeks 168 and 192)
The EDSS-Expanded Disability Status Scale is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death). Disability progression as measured by EDSS is defined as ≥1 point increase in EDSS score from a baseline EDSS score of 1-5 inclusive, a 0.5-increase from a baseline EDSS score higher than 5 and a 1.5-increase from a baseline EDSS score from 0 to 1 exclusive. Disability progression was considered confirmed if a sustained change in EDSS for a minimum of 24 weeks (-2 weeks) from the initial progression event was seen i.e. the change in EDSS must have been sustained at all available visits (during Year 1) for a minimum of 24 weeks/48 weeks. Percentage of participants who did not have CPD sustained for 24 and 48 weeks are reported here.
Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 1, As Measured Using EDSS
时间窗: Year 1 (Week 48)
Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 2, As Measured Using EDSS
时间窗: Year 2 (Week 96)
Percentage of Participants Who Have Improved, Stable, or Worsened Disability at Year 3, As Measured Using EDSS
时间窗: Year 3
Percentage of Participants Who Have Improved, Stable, or Worsened Disability at Year 4, As Measured Using EDSS
时间窗: Year 4
Mean Change From Baseline in EDSS Score at Week 24
时间窗: From Baseline to Week 24
Mean Change From Baseline in EDSS Score at Week 48
时间窗: From Baseline to Week 48
Mean Change From Baseline in EDSS Score at Week 72
时间窗: From Baseline to Week 72
Percentage of Participants Without Protocol-Defined Event of Disease Activity
时间窗: Baseline up to 4 years
Protocol-defined event of disease activity is defined as having at least one of the following: (1). protocol defined relapse (occurrence of new or worsening neurological symptoms attributable to Multiple Sclerosis \[MS\], as determined using EDSS/Functional Systems Score \[FSS\] assessment). (2). CDP, as determined using EDSS. (3). a T1 Gd-enhanced lesion after Week 8 (4). a new and/or enlarging T2 hyperintense lesion on magnetic resonance imaging (MRI) after Week 8 compared to the Week 8 MRI scan.
次要结局
- Substudy: IRRs Leading to Treatment Discontinuation(From Week 24 to Week 144)
- Percentage of Participants With no Evidence of Progression Sustained for At Least 24 Weeks and no Active Disease (NEPAD)(Weeks 96, 192)
- Substudy: Severity of IRRs(From Week 24 to Week 144)
- Percentage of Participants Without Protocol-defined Event of Evidence of Progression (NEP)(Weeks 96, 192)
- Percentage of Participants Who Are Relapse Free(Week 192)
- Percentage of Participants With No Evidence of Protocol Defined Disease Activity(Weeks 96, 144, 192)
- Secondary: Change From Baseline in Multiple Sclerosis Functional Composite Score (MSFC) Total(Weeks 24, 48, 72, 96, 120, 144, 168, 192)
- Change From Baseline in MSFC Composite Timed 25 Foot Walk Test (T25FW) Score.(Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192)
- Change From Baseline in MSFC Composite 9 Hole Peg Test (9HPT) Score(Weeks 24, 48, 72, 96, 120, 144, 168, 192)
- Change From Baseline in MSFC Composite (Paced Auditory Serial Addition Test [PASAT]) Score(Weeks 24, 48, 72, 96, 120, 144, 168, 192)
- Change From Baseline in Cognitive Performance as Measured by Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) - Symbol Digits Modalities Test (SDMT)(Baseline, Weeks 48, 96, 144, 192)
- Change From Baseline in Cognitive Performance as Measured by BICAMS -California Verbal Learning Test-II (CVLT-II)(Baseline, Weeks 48, 96, 144, 192)
- Change From Baseline in Cognitive Performance as Measured by BICAMS - Brief Visuospatial Memory Test-Revised (BVMT-R)(Baseline, Weeks 48, 96, 144, 192)
- Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI(Weeks 24, 48, 96, 144, 192)
- Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI(Baseline, Weeks 24, 48, 96, 144, 192)
- Change From Baseline in Total T1 Hypointense Lesion Volume as Detected by Brain MRI(Baseline, Weeks 48, 96, 144, 192)
- Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI(Baseline, Weeks 8, 24, 48, 96, 144, 192)
- Change From Baseline in Brain Volume as Detected by Brain MRI(From Baseline to Weeks 24, 48, 96, 144, 192)
- Percentage of Participants Without Treatment Discontinuation(Baseline up to 4 years)
- Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score(Baseline, Weeks 24, 48, 96, 120, 144, 192)
- SymptoMScreen Composite Score(Baseline, Weeks 24, 48, 96, 144, 192)
- Quality of Life: Multiple Sclerosis Impact Scale (MSIS)-29 Questionnaire Score(Baseline, Weeks 24, 48, 96, 144, 192)
- Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Baseline up to 4 years)
- Substudy: Number of Participants With IRR Overall and by Dose at Randomization(From Week 24 to Week 144)
- Substudy: Number of IRR Symptoms(From Week 24 to Week 144)