Study Evaluating Rebif, Copaxone, and Tysabri for Active Multiple Sclerosis

Study Overview
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Brief Summary
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This was a multicenter, randomized, open-label, parallel-group, active-controlled study. Prior to randomization, participants were to have been treated with glatiramer acetate or interferon β-1a (44 μg). Participants were to be randomized to receive natalizumab, interferon β-1a 44 μg, or glatiramer acetate.

Detailed Description
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The protocol was amended in 15 March 2011 to discontinue participants' enrollment and efficacy assessments, and to offer the opportunity for participants already enrolled to continue receiving study treatment for their planned participation in the study. The study had been active in several countries for approximately 1 year, and enrollment had been significantly slower than expected. Thus, the decision was made by the Sponsor to terminate the study since current and projected future enrollment rates would not have provided valuable information in a reasonable timeframe. All clinical efficacy and magnetic resonance imaging (MRI) procedures were removed from the protocol, and safety assessments were to be managed through standard of care activities.

Official Title
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A Multicenter, Randomized, Open-Label, Parallel-Group, Active-Controlled Study to Evaluate the Benefits of Switching Therapy (Glatiramer Acetate or Interferon Beta-1a) to Natalizumab in Subjects With Relapsing Remitting Multiple Sclerosis

Conditions
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Relapsing Remitting Multiple Sclerosis

Intervention / Treatment
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* Drug: BG00002 (natalizumab)
* Drug: interferon beta-1a
* Drug: glatiramer acetate


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Have a diagnosis of relapsing remitting multiple sclerosis (MS) as defined by the revised McDonald Committee criteria (Polman 2005). Must have been treated with a stable regimen of either glatiramer acetate (20 mg per day subcutaneous) or interferon beta-1a (44 mcg 3 times per week subcutaneous) as their principal first therapy for MS for 6 to 18 months prior to randomization. (Note: prior treatment with another MS therapy of ≤ 30 days total duration is not exclusionary [e.g. titration to 44 mcg is allowed]). Have had disease activity within 12 months prior to screening while on therapy; disease activity must be observed after a minimum of 6 months on therapy. Qualifying disease activity is defined as: One or more clinical relapses OR Two or more new MRI lesions (gadolinium [Gd+] and/or T2 hyperintense) For inclusion purposes: (a) a relapse is defined as neurologic signs and/or symptoms documented in the medical record by a neurologist and of sufficient duration to be determined by the Investigator or the Treating Physician as consistent with an MS relapse or (b) MRI activity must be verified by the central reader center. Be naïve to natalizumab. Have a documented Expanded Disability Status Scale (EDSS) score between 0.0 and 5.5, inclusive. Key Exclusion Criteria: Have a diagnosis of primary progressive, secondary progressive, or progressive relapsing MS (as defined by Lublin and Reingold, 1996). These conditions require the presence of continuous clinical disease worsening over a period of at least 3 months. Patients with these conditions may also have superimposed relapses, but are distinguished from relapsing-remitting patients by the lack of clinically stable periods or clinical improvement. Have known intolerance, contraindication to, or history of non-compliance with, the use of glatiramer acetate or interferon beta-1a. Have had an MS exacerbation (relapse) within 30 days prior to randomization AND/OR the patient has not stabilized from a previous relapse, in the opinion of the Investigator, prior to randomization. The patient is considered by the Investigator to be immunocompromised based on medical history, physical examination, laboratory testing, or due to prior immunosuppressive or immunomodulating treatment. Subjects for whom MRI is contraindicated, i.e., have pacemakers or other contraindicated implanted metal devices, have suffered or are at risk for side effects from gadolinium (Gd), or have claustrophobia that cannot be medically managed. History of any clinically significant (as determined by the Investigator) cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, or other major disease that would preclude participation in a clinical trial. History of malignant disease, including solid tumors and hematologic malignancies (with the exception of basal cell and squamous cell carcinomas of the skin that have been completely excised and are considered cured). Known history of human immunodeficiency virus (HIV). Positive test result for hepatitis C virus (test for hepatitis C virus antibody [HCVAb]) or hepatitis B virus (test for hepatitis B surface antigen [HBsAg] and/or hepatitis B core antibody [HBcAb]). History of transplantation or any anti-rejection therapy. History of progressive multifocal leukoencephalopathy (PML). NOTE: Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Natalizumab<br> | Drug: BG00002 (natalizumab)<br>* 300 mg intravenous injection every 4 weeks<br>* Other names: Tysabri;|
| Active Comparator: Interferon Beta-1a<br> | Drug: interferon beta-1a<br>* 44 mcg subcutaneous injection 3 times per week<br>* Other names: Rebif;|
| Active Comparator: Glatiramer Acetate<br> | Drug: glatiramer acetate<br>* 20 mg subcutaneous injection once daily<br>* Other names: Copaxone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-emergent Serious Adverse Events (SAEs) | An SAE was defined as any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the subject at immediate risk of death (a life-threatening event; however, this does not include an event that, had it occurred in a more severe form, might have caused death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or results in a congenital anomaly/birth defect. An SAE may also have been any other medically important event that, in the opinion of the Investigator, may jeopardize the subject or may require intervention to prevent one of the other outcomes listed in the definition above. See Adverse Events section below for further details. | up to 108 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MS