A Phase 3 Randomized, Rater-Blinded Study Comparing Two Annual Cycles of Intravenous Alemtuzumab to Three-Times Weekly Subcutaneous Interferon Beta-1a (Rebif®) in Treatment-Naïve Patients With Relapsing-Remitting Multiple Sclerosis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 581
- 试验地点
- 106
- 主要终点
- Percentage of Participants With Sustained Accumulation of Disability (SAD)
研究概览
简要总结
The purpose of this study was to establish the efficacy and safety of alemtuzumab (Lemtrada™) as a treatment for relapsing-remitting multiple sclerosis (MS), in comparison with subcutaneous (SC) interferon beta-1a (Rebif®). The study had enrolled participants who had not previously received MS disease-modifying therapies. Participants had monthly laboratory tests and comprehensive testing every 3 months.
详细描述
Every participant had received active treatment; there was no placebo. Participants who qualified were randomly assigned to treatment with either alemtuzumab or SC interferon beta-1a at a 2:1 ratio (that is, 2 given alemtuzumab for every 1 given interferon beta-1a). Alemtuzumab was administered in two annual courses, once at the beginning of the study and again 1 year later. Interferon beta-1a was self-injected 3 times per week for 2 years. All participants were required to return to their study site every 3 months for neurologic assessment. In addition, safety-related laboratory tests were performed at least monthly. Participation in this study ended 2 years after the start of treatment for each participant. Additionally, participants who received alemtuzumab might be followed in CAMMS03409 (NCT00930553) an extension study for safety and efficacy assessments. Participants who received interferon beta-1a and completed 2 years on study might be eligible to receive alemtuzumab on the extension study.
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Given written/signed informed consent
- •Age 18 to 50 years old (inclusive) as of the date the informed consent form (ICF) was signed
- •Diagnosis of MS per updated McDonald criteria, and cranial magnetic resonance imaging (MRI) scan demonstrating white matter lesions attributable to MS within 5 years of screening
- •Onset of MS symptoms (as determined by a neurologist, either at screening or retrospectively) within 5 years of the date the ICF was signed
- •Expanded Disability Status Scale (EDSS) score 0.0 to 3.0 (inclusive) at screening
- •Greater than or equal to (>=) 2 MS attacks (first episode or relapse) occurring in the 24 months prior to the date the ICF was signed, with >=1 attack in the 12 months prior to the date the ICF was signed, with objective neurological signs confirmed by a physician, nurse practitioner, or other Genzyme-approved health-care provider and the objective signs could be identified retrospectively
排除标准
- •Received prior therapy for MS other than corticosteroids, for example, alemtuzumab, interferons, intravenous immunoglobulin, glatiramer acetate, natalizumab, and mitoxantrone
- •Exposure to azathioprine, cladribine, cyclophosphamide, cyclosporine A, methotrexate, or any other immunosuppressive agent other than systemic corticosteroid treatment
- •Any progressive form of MS
- •History of malignancy (except basal skin cell carcinoma)
- •CD4 + , CD8 + count, B cell, or absolute neutrophil count less than (<) lower limit of normal (LLN) at screening
- •Known bleeding disorder (for example, dysfibrinogenemia, factor IX deficiency, hemophilia, Von Willebrand's disease, disseminated intravascular coagulation, fibrinogen deficiency, or clotting factor deficiency)
- •Significant autoimmune disease including but not limited to immune cytopenias, rheumatoid arthritis, systemic lupus erythematosus, other connective tissue disorders, vasculitis, inflammatory bowel disease, severe psoriasis
- •Presence of anti-thyroid stimulating hormone (TSH) receptor (TSHR) antibodies (that is, above the LLN)
- •Active infection or at high risk for infection
结局指标
主要结局
Percentage of Participants With Sustained Accumulation of Disability (SAD)
时间窗: Up to 2 years
EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score: 0 (normal neurological examination) to 10 (death due to MS). As measured by EDSS score, SAD was defined as increase of at least 1.5 points for participants with Baseline score of 0 and increase of at least 1.0 point for participants with a Baseline score of 1.0 or more; and the increase persisted for at least next 2 scheduled assessments, that is, 6 consecutive months. Onset date of SAD was date of first EDSS assessment that began 6 month consecutive period of SAD. Participants who did not reach SAD endpoint were censored at their last visit. Percentage of participants with SAD, estimated by Kaplan-Meier (KM) method, was reported.
Annualized Relapse Rate
时间窗: Up to 2 years
Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to multiple sclerosis that lasted for at least 48 hours, that were present at normal body temperature, and that were preceded by at least 30 days of clinical stability. Annualized relapse rate was estimated through negative binomial regression with robust variance estimation and covariate adjustment for geographic region using observed number of relapses as dependent variable, the log total amount of follow-up from date of first study treatment for each participant as an offset variable, and treatment group and geographic region as model covariates.
次要结局
- Percentage of Participants Who Were Relapse Free at Year 2(Year 2)
- Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Year 2(Baseline, Year 2)
- Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score at Year 2(Baseline, Year 2)
- Percent Change From Baseline in Magnetic Resonance Imaging Time Constant 2 (MRI-T2) Hyperintense Lesion Volume at Year 2(Baseline, Year 2)