Observational Study of Tysabri in Early Relapsing-Remitting Multiple Sclerosis in Anti-JC Virus Antibody Negative Participants

Biogen231 enrolled

Overview

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 \[MSIS-29\])

Study Type

OBSERVATIONAL

Enrollment

231

Conditions

Relapsing-Remitting Multiple Sclerosis

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * 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. Key Exclusion Criteria: * 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.

Outcomes

Primary Outcomes

Proportion of Participants who are overall disease activity-free at 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.

Time frame: Baseline and Months 12 and 24

Proportion of participants who are clinical disease activity-free at Months 36 and 48

Clinical disease activity-free is defined as no sustained EDSS progression and no relapses at Month 36 and 48.

Time frame: Baseline and Months 36 and 48

Secondary Outcomes

Identification of baseline prognostic factors that predict overall disease-free status

Time frame: Baseline and Month 12

Identification of yearly overall disease-free response factors that predict overall disease-free status

Time frame: Month 12 and Month 24

Number of Participants with Clinical Disease-Free Status Measured by Relapses

A clinical relapse is a 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.

Time frame: Months 12, 24, 36, and 48

Identification of baseline prognostic factors that predict clinical disease-free status

Time frame: Month 12

Identification of yearly clinical disease-free response factors that predict clinical disease-free status

Time frame: Months 24, 36 and 48

Annualized Relapse Rate

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. The ARR will be calculated by tabulating the total number of relapses experienced in the group divided by the number of days up to the end of study, and the ratio then multiplied by 365.

Time frame: Months 12, 24, 36, and 48

Percentage of participants with Sustained EDSS progression