A Multicenter, Observational, Open-Label, Single-Arm Study of Tysabri in Early Relapsing-Remitting Multiple Sclerosis in Anti-JCV Antibody Negative Patients
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- Biogen
- 入组人数
- 231
- 试验地点
- 1
- 主要终点
- Proportion of Participants who are overall disease activity-free at Months 12 and 24
研究概览
简要总结
The primary objective of the study is to determine which baseline and yearly response factors (clinical and para clinical) predict overall disease-free status at Month 12 and Month 24, and clinical disease-free status in subsequent Months 36 and 48. The secondary objectives are: To identify prognostic factors at Baseline that predict overall disease-free status at Month 12, and to assess if yearly overall disease-free response factors predict overall disease-free status at Month 24; To evaluate clinical disease-free status (relapse, Expanded Disability Status Scale [EDSS]) at each analysis time point of Months 12, 24, 36, and 48; To identify prognostic factors at Baseline that predict clinical disease-free status at Month 12, and to assess yearly clinical disease-free response factors that predict clinical disease-free status (relapse, EDSS) in subsequent years at Months 24, 36, and 48; To evaluate the impact of Tysabri at each analysis time point of Months 12, 24, 36, and 48 on the following: annualized relapse rate (ARR), sustained EDSS progression and improvement (24-week sustained); To evaluate the impact of Tysabri at each analysis time point of Months 12, 24, 36, and 48 on the following: magnetic resonance image (MRI) measures: T2, T1, T1 with Gadolinium (Gd), brain atrophy; To evaluate the impact of Tysabri at Month 24 and Month 48 on the following: optical coherence tomography (OCT), Low and High Contrast Visual Acuity Assessment; To evaluate the impact of Tysabri at each analysis time point of Months 12, 24, 36, and 48 on the following: cognitive impairment (Symbol Digit Modalities Test [SDMT]), capacity for work (Work Productivity and Activity Impairment Questionnaire [WPAI]), quality of life (QoL) (Multiple Sclerosis Impact Scale [MSIS-29])
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented diagnosis of Relapsing Multiple Sclerosis (McDonald 2010 Criteria ).
- •<3 year disease duration.
- •Must have an Expanded Disability Status Scale (EDSS) score from 0 to 4.0, inclusive.
- •Anti-JCV antibody negative test within 6 months of Screening Visit.
- •Must satisfy the approved therapeutic indications for Tysabri.
- •Must be treatment-naïve to disease-modifying therapy (DMT) or have been treated with DMT (including but not limited to Avonex, Betaseron, Rebif, Copaxone, Extavia, or Gilenya) for ≤36 months total prior to date of informed consent.
- •Decision to treat with Tysabri must precede enrollment.
排除标准
- •Any prior treatment with Tysabri.
- •Anti-JCV antibody positive at any timepoint prior to the Screening Visit.
- •Contraindications to treatment with Tysabri as described in the US Prescribing Information.
- •History of progressive multifocal leukoencephalopathy (PML) or other opportunistic infections, or an increased risk for such infections.
- •History of diagnosis of Primary Progressive Multiple Sclerosis (PPM) and/or Secondary Progressive Multiple Sclerosis (SPMS).
- •Receiving immunomodulatory or immunosuppressive therapy.
- •Prior history of immunosuppressive use (mitoxantrone, azathioprine, methotrexate, cyclophosphamide, mycophenolate, cladribine, rituximab).
- •Immunocompromised at the time of enrollment.
- •Known active malignancies (subjects with cutaneous basal cell carcinoma that has been completely excised prior to study entry remain eligible).
- •Women breastfeeding, pregnant, or planning to become pregnant; women who are not post-menopausal or surgically sterile who are unwilling to practice contraception.
- •Inability to comply with study requirements.
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
结局指标
主要结局
Proportion of Participants who are overall disease activity-free at Months 12 and 24
时间窗: Baseline and Months 12 and 24
Overall disease activity-free is defined as no relapses, no disability progression (RRMS), and absence of MRI disease activity (no gadolinium \[gd\])+ lesions, no new or enlarging T2-hyperintense lesions). A clinical relapse is defined as new or recurrent neurological symptoms, not associated with fever, lasting for at least 24 hours, and followed by a period of 30 days of stability or improvement. Sustained disability progression defined by at least a 1.0-point increase on the EDSS from a Baseline EDSS ≥1.0 that is sustained for 12 or 24 weeks, or at least a 1.5-point increase on the EDSS from a Baseline EDSS \<1.0 that is sustained for 12 or 24 weeks. The EDSS measures the disability status of people with multiple sclerosis on a scale that ranges from 0 to 10, with higher scores indicating more disability.
Proportion of participants who are clinical disease activity-free at Months 36 and 48
时间窗: Baseline and Months 36 and 48
Clinical disease activity-free is defined as no sustained EDSS progression and no relapses at Month 36 and 48.
次要结局
- Identification of baseline prognostic factors that predict overall disease-free status(Baseline and Month 12)
- Identification of yearly overall disease-free response factors that predict overall disease-free status(Month 12 and Month 24)
- Percentage of participants with Sustained EDSS progression(Baseline and Months 12, 24, 36, and 48)
- MRI brain atrophy as assessed by MRI(Baseline and Months 12, 24, 36, and 48)
- Change from baseline in low contrast visual acuity(Baseline and Month 24 and Month 48)
- Quality of Life as measured by MSIS-29(Baseline and Months 12, 24, 36 and 48)
- Number of Participants with Clinical Disease-Free Status Measured by Relapses(Months 12, 24, 36, and 48)
- Identification of baseline prognostic factors that predict clinical disease-free status(Month 12)
- Identification of yearly clinical disease-free response factors that predict clinical disease-free status(Months 24, 36 and 48)
- Sustained EDSS improvement(Baseline and Months 12, 24, 36, and 48)
- Change form baseline in number of new or newly enlarging T2 hyperintense lesions as assessed by MRI(Baseline and Months 12, 24, 36, and 48)
- Change from baseline in number of new T1 hypointense lesions as assessed by MRI(Baseline and Months 12, 24, 36, and 48)
- Change form baseline in number of T1 lesions with Gd-enhancing lesions as assessed by MRI(Baseline and Months 12, 24, 36, and 48)
- Change from baseline in retinal nerve fiber layer (RNFL) thickness as assessed by OCT(Baseline and Month 24 and Month 48)
- Cognitive impairment as assessed by change from baseline in SDMT(Baseline and Months 12, 24, 36 and 48)
- Capacity for work as assessed by change from baseline in WPAI questionnaire(Baseline and Months 12, 24, 36 and 48)
- Annualized Relapse Rate(Months 12, 24, 36, and 48)
- Change from baseline in high contrast visual acuity(Baseline and Month 24 and Month 48)
- Number of Participants with Clinical Disease-Free Status Measured by EDSS(Months 12, 24, 36 and 48)