Study of Tysabri in Early Relapsing Remitting Multiple Sclerosis Participants

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the impact of an early treatment with Natalizumab on the management of the progressive nature of Relapsing Remitting Multiple Sclerosis (RRMS).

Official Title
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Tysabri in Early Relapsing Remitting Multiple Sclerosis Patients - TYPIFI (Tysabri Patient Initiation After Failure of the Initial DMT)

Conditions
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Relapsing Remitting Multiple Sclerosis

Intervention / Treatment
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* Drug: Natalizumab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Documented diagnosis of Relapsing Remitting Multiple Sclerosis (McDonald 2010 Criteria). EDSS ≤ 3.0. Must fulfill Tysabri indication (relapse and MRI criteria). Decision to start treatment with Natalizumab must precede enrollment. Up to four natalizumab infusions. Key Exclusion Criteria: Any prior treatment with Natalizumab. Prior imunossupressive treatment (Mitoxantrone, Azathioprine, Methotrexate, Cyclophosphamide, Mycophenolate, Cladribine, Rituximab). Contraindications to treatment with Natalizumab. History of Progressive Multifocal Leukoencephalopathy (PML) or other opportunistic infections, or an increased risk for such infections. Immunocompromised at the time of enrollment. Known active malignancies. Inability to comply with study requirements. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Natalizumab<br>Natalizumab 300 mg is administered by intravenous infusion once every 4 weeks. | Drug: Natalizumab<br>* As described in the treatment arm.<br>* Other names: BG00002;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Disease-Free Status at Month 12 |  | Month 12 | 
| Clinical Disease-Free Status at Month 12 in Comparison to the Previous Year |  | Month 12 | 
| Annualized Relapse Rate at Month 12 in Comparison to the Previous Year |  | Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Disease-Free Status at Months 24, 36 and 48 |  | Months 24, 36 and 48 | 
| Clinical Disease-free Status Every 6 Months |  | Every 6 months (Up to 48 months) | 
| Annualized Relapse Rate (ARR) |  | Months 12, 24, 36 and 48 | 
| Change From Baseline in Sustained Expanded Disability Status Scale (EDSS) Score (24-week Sustained) | The EDSS is used to quantify disability due to symptoms of MS and to track changes in disability status over time. Scores range from 0 (normal neurological exam) to 10 (death due to multiple sclerosis). | Months 12, 24, 36 and 48 | 
| MRI measures: T2, T1, T1 with Gadolinium (Gd) |  | Months 12, 24, 36 and 48 | 
| Cognitive Impairment Using Symbol Digit Modalities Test (SDMT) |  | Months 12, 24, 36 and 48 | 
| Change From Baseline in Ability to Work and Productivity as Assessed by Work Productivity and Activity Impairment (WPAI) Questionnaire | The WPAI questionnaire is a validated instrument to measure impairments in work and activities. The WPAI yields four types of scores: 1. Absenteeism (work time missed) 2. Presenteesism (impairment at work / reduced on-the-job effectiveness) 3. Work productivity loss (overall work impairment / absenteeism plus presenteeism) 4. Activity Impairment. WPAI outcomes are expressed as impairment percentages ranging from 0-100%, with higher numbers indicating greater impairment and less productivity. | Months 12, 24, 36 and 48 | 
| Quality of life (QoL) Assessed Using Fatigue Severity Scale | The FSS is a self-assessment questionnaire that provides a score as a measurement of the severity of fatigue. It consists of 9 questions scored from 1 to 7. A low value (e.g., 1); indicates strong disagreement with the statement, whereas a high value (e.g., 7); indicates strong agreement. A total score of 36 or more suggests presence of fatigue. | Months 12, 24, 36 and 48 | 
| QoL assessed using Multiple Sclerosis Functional Composite (MSFC) Test | MSFC has 2 component- timed 25-foot walk (T25FW) and 9-hole peg test (9HPT) [dominant and nondominant hands]. The MSFC Z-score is calculated by creating Z-scores for each component of the MSFC and averaging them to create an overall composite score. MSFC Z-score = (Z25-foot-walk + Z9HPT-2)/2, where Zj refers to Z-scores of component j. A Z-score represented the number of standard deviations participant's test result was higher (Z >0) or lower (Z <0) than the average test result (Z = 0) from the reference population. Higher scores indicate better outcomes. | Months 12, 24, 36 and 48 | 
| QoL Assessed Using Beck Depression Inventory, 2nd Edition (BDI-II) | BDI-II Scale is a 21-item self-reported questionnaire which measures the existence and severity of symptoms of depression. Each of the 21 items on BDI-II tool represents a depressive symptom. The symptoms are each scored on a 4-point Likert scale of 0 to 3 (0=symptom is absent; 3=symptom is severe). Scores for each symptom are added up to obtain the total scores for all 21 items. Total score ranges from 0-63; of which 0-8 is considered no depression, 0-13 is minimal depression, 14-19 is mild depression, 20-28 is moderate depression and 29-63 is severe depression. | Months 12, 24, 36 and 48 | 
| QoL Assessed Using Multiple Sclerosis Impact Scale (MSIS-29) | MSIS-29 is a brief self-administered instrument measuring physical (20 items) and psychological (9 items) impact of Multiple Sclerosis (MS). Each of the 29 items on MSIS-29 tool is a question that ask for participants views about the impact of MS on their day to day lives. Each item is scored on 1 to 5 (1=Not at all; 5=Extremely). | Months 12, 24, 36 and 48 |