Natalizumab High Titer Immunogenicity and Safety

Study Overview
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Brief Summary
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The primary objective of the study was to evaluate the immunogenicity of natalizumab (Tysabri®) produced by a modified manufacturing process (natalizumab high titer; BG00002-E) administered intravenously (IV) to participants with relapsing forms of multiple sclerosis (MS). The secondary objective of this study was to evaluate the safety of natalizumab high titer.

Official Title
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A Multicenter, Open-Label Immunogenicity and Safety Study of Natalizumab High Titer Material (BG00002-E) in Subjects With Relapsing Forms of Multiple Sclerosis

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Biological: BG00002-E (natalizumab high titer)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of a relapsing form of MS Must fall within the therapeutic indications stated in the locally approved label for natalizumab Other protocol-defined inclusion criteria may apply Exclusion Criteria: Prior treatment with natalizumab Considered by investigator to be immunocompromised Other protocol-defined 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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Design Details

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Natalizumab High Titer<br>natalizumab high titer 300 mg administered as intravenous (IV) infusion over 60 minutes once every 4 weeks for up to 9 doses | Biological: BG00002-E (natalizumab high titer)<br> <br> * Other names: Tysabri;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Anti-Natalizumab Antibody Negative, Transient Positive, and Persistent Positive Status | Negative: no detectable antibody at all post-baseline visits. Persistent positive: antibody positive at 2 or more post-baseline visits at least 42 days apart, or positive at the last post-baseline visit. Transient positive: antibody positive at only 1 post-baseline visit prior to the last visit. | Assessed every 12 weeks from Week 0 (Baseline) to Week 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs | AE: any sign, symptom, or diagnosis/disease that was unfavorable or unintended, new, or if pre-existing, worsened in a participant administered a study treatment and that did not necessarily have a causal relationship with this treatment. SAE: an event that resulted in death; an event that, in the view of the investigator, placed the participant at immediate risk of death (life-threatening event); an outcome that resulted in a congenital anomaly/birth defect diagnosed in a child of a participant in this study; an event that required or prolonged inpatient hospitalization; an event that resulted in persistent or significant disability/incapacity; any other medically important event that, in the opinion of the investigator, may have jeopardized the participant or may have required intervention to prevent one of the other outcomes listed above. Events were classified as 'related' or 'not related' to study drug, and categorized as 'mild' moderate' or 'severe' per protocol. | AEs: collected from Baseline (Week 0) until Week 36 or premature withdrawal. SAEs: collected from informed consent until Week 36 or premature withdrawal. | 
| Mean Change From Baseline in Expanded Disability Status Scale (EDSS) Scores at Week 36 | EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. The change in EDSS at Month 36 was calculated as EDSS at Month 36 minus EDSS at baseline. | Baseline, Week 36 | 
| Annualized Relapse Rate | Annualized relapse rate was calculated as the total number of relapses that occurred during the study divided by the total number of years the participant was followed in the study. The annualized relapse rate was based only on those relapses that were determined to meet the definition of relapse per the investigator's clinical judgment. New or recurrent symptoms that occurred less than 30 days following the onset of a protocol-defined relapse were considered part of the same relapse. | Through Week 36 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tysabri, natalizumab, Multiple Sclerosis, Relapsing Forms of Multiple Sclerosis