Evaluation of the Onset of Action in Highly Active MS (MAGNIFY)

Study Overview
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Brief Summary
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The main purpose of the study was to determine the onset of Mavenclad® action by frequent magnetic resonance imaging (MRI) assessment of the combined unique active (CUA) lesions in participants with highly active relapsing multiple sclerosis (MS).

Official Title
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A 2-year Prospective Study to Evaluate the Onset of Action of Mavenclad® in Subjects With Highly Active Relapsing Multiple Sclerosis (MAGNIFY)

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Mavenclad®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Highly active RMS as defined by: One relapse in the previous year and at least 1 T1 Gadolinium (Gd)+ lesion or 9 or more T2 lesions, while on therapy with other disease modifying drugs (DMDs) Two or more relapses in the previous year, whether on DMD treatment or not. Expanded Disability Status Scale (EDSS) score less than equals to (<=) 5.0. Other protocol defined inclusion criteria could apply. Exclusion Criteria: Previous exposure to drugs such as fingolimod, natalizumab, alemtuzumab, mitoxantrone and ocrelizumab. Positive hepatitis C or hepatitis B surface antigen test and/or hepatits B core antibody test for immunoglobulin G (IgG) and/or immunoglobulin M (IgM). Current or previous history of immune deficiency disorders including a positive human immunodeficiency virus (HIV) result. Currently receiving immunosuppressive or myelosuppressive therapy with, for example, monoclonal antibodies, methotrexate, cyclophosphamide, cyclosporine or azathioprine, or chronic use of corticosteroids. History of tuberculosis , presence of active tuberculosis, or latent tuberculosis Evidence or suspect of Progressive Multifocal Leukoencephalopathy (PML) in Magnetic Resonance Imaging (MRI). Active malignancy or history of malignancy. Other protocol defined exclusion criteria could apply.

Ages Eligible for Study
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Minimum Age: 18 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

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mavenclad®<br> | Drug: Mavenclad®<br>* Participants received Mavenclad® 3.5 milligram per kilogram (mg/kg) of body weight over 2 years, administered as 1 treatment course of 1.75 mg/kg per year.<br>* Other names: Cladribine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline Period (Period Screening to Baseline) in Counts of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions at Period 1 (Month 1-6) | CUA lesions were measured by using MRI scans. | Baseline period (the period screening to Baseline), Period 1 (Month 1-6) | 
| Change From Baseline Period (Period Screening to Baseline) in Counts of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions at Period 2 (Month 2-6) | CUA lesions were measured by using MRI scans. | Baseline period (the period screening to Baseline), Period 2 (Month 2-6) | 
| Change From Baseline Period (Period Screening to Baseline) in Counts of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions at Period 3 (Month 3-6) | CUA lesions were measured by using MRI scans. | Baseline period (the period screening to Baseline), Period 3 (Month 3-6) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Counts of Immune Cell Subsets - B Cells at Month 3, 6, 12, 15, 18 and 24 | B cell population counts are: CD19 B cells (TBNK panel), CD20 B cells (B cell panel), Memory B cells (B cell panel), Activated B cells (B cell panel), Total plasma cells (B cell panel), Short-lived plasma cells (B cell panel), Naïve B cells (B cell panel), Transitional B cells (B cell panel), and Regulatory B cells (B cell panel). | Baseline, Month 3, 6, 12, 15, 18 and 24 | 
| Percent Change From Baseline in Counts of Immune Cell Subsets - T Cells at Month 3, 6, 12, 15, 18 and 24 | T cell population counts are: Total CD4 T cells (TBNK panel), CD4 Th1 cells (T cell panel), CD4 Th17 T cells (T cell panel), CD4 Regulatory T cells (T cell panel), and Total CD8 T cells (TBNK panel). | Baseline, Month 3, 6, 12, 15, 18 and 24 | 
| Percent Change From Baseline in Counts of Immune Cell Subsets - NK Cells at Month 3, 6, 12, 15, 18 and 24 | NK cell population counts are: CD16+ CD56+ NK Cells, CD16+ NK Cells, NK p46 cells, CD16lowCD56bright, and CD16brightCD56dim. | Baseline, Month 3, 6, 12, 15, 18 and 24. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple sclerosis, Mavenclad ®, Cladribine