Effect of BG00012 on Lymphocyte Subsets and Immunoglobulins in Subjects With Relapsing Remitting Multiple Sclerosis (RRMS).

Study Overview
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Brief Summary
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The primary objective of the study is to evaluate the effect of BG00012 on lymphocyte subset counts during the first year of treatment in subjects with relapsing-remitting multiple sclerosis (RRMS). A secondary objective is to evaluate the pharmacodynamic effect on absolute lymphocyte counts (ALCs) and immunoglobulins (Igs) during the first year of treatment.

Official Title
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An Open-Label Study to Assess the Effects of BG00012 on Lymphocyte Subsets in Subjects With Relapsing-Remitting Multiple Sclerosis

Conditions
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Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis

Intervention / Treatment
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* Drug: dimethyl fumarate


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Subjects of childbearing potential (including female subjects who are post-menopausal for less than 1 year) must practice effective contraception during the study and be willing and able to continue contraception for 30 days after their last dose of study treatment. Must have a confirmed diagnosis of RRMS according to the revised McDonald criteria (2010) [Polman 2011] Key Exclusion Criteria: History of or positive test result at Screening for: human immunodeficiency virus hepatitis C virus antibody hepatitis B infection Drug or alcohol abuse within 1 year prior to Screening. Prior treatment with any of the following: cladribine mitoxantrone total lymphoid irradiation alemtuzumab T-cell or T-cell receptor vaccination any therapeutic monoclonal antibody, with the exception of natalizumab or daclizumab Treatment with any of the following medications or procedures within 6 months prior to Baseline (Day 1): DMF (given as Fumaderm®) or BG00012; enrollment will be limited to no more than 40 subjects (out of 200) with prior DMF exposure cyclosporine azathioprine methotrexate mycophenolate mofetil intravenous (IV) Ig plasmapheresis or cytapheresis NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: dimethyl fumarate<br>120 mg twice daily (BID) for the first 7 days and 240 mg BID thereafter | Drug: dimethyl fumarate<br>* Initial oral dose for 7 days with maintenance dose thereafter<br>* Other names: DMF;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Lymphocyte Subsets Counts up to 48 Weeks: T Cell, B Cell, Natural Killer Cell (TBNK) | Lymphocyte subsets include T cell, B cell and Natural killer (NK) cells. | Baseline, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48 | 
| Change From Baseline in Lymphocyte Subsets Counts up to 48 Weeks: T-Cells Subsets | T-cells subsets includes Activated CD4+ T-cell, Activated CD8+ T-cell, Activated CD8+ T-cell [CD38+], Activated Th (T helper) 1 phenotype, Activated Th17 phenotype, Activated Th2-enriched phenotype, Activated CD4+ T-cell [CD38+HLA-DR+], Activated CD4+ T-cell [HLA-DR+], Activated CD8+ T-cell [HLA-DR+], Central Memory (CM) CD4+ T-cell [CD45RA-CCR7+], CM CD4+ T-cell [CD45RA-CCR7+], CM CD8+ T-cell [CD45RA-CCR7+], Effector CD4+ T-cell [CD45RA+CCR7-], Effector CD8+ T-cell [CD45RA+CCR7-], Effector Memory (EM) CD4+ T-cell [CD45RA-CCR7-], EM CD8+ T-cell [CD45RA-CCR7-], Effector Regulatory T-cells, Effector CD4+ T-cell [CD45RA+CCR7-], Effector CD8+ T-cell [CD45RA+CCR7-], Naïve CD4+ T-cell [CD45RA+], Naïve CD8+ T-cell [CD45RA+], Naïve (N) CD8+ T-cell [CD45RA+], Naïve Regulatory T-cells, Terminal Effector Regulatory T-cells, Th1 phenotype, Th17 phenotype, Th2-enriched phenotype. Here, Change at week is represented as CW. | Baseline, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48 | 
| Change From Baseline in Lymphocyte Subsets Counts up to 48 Weeks: B-Cell Subsets | B-cell subsets include CD10+ Transitional B cells, CD138+ Plasma Cells, Ig (Immunoglobulin) D+ Memory B cells [non-class switched], IgD- Memory B cells [class switched], Naïve B cells, Plasma Cells [CD10-], Transitional B-cells and Plasmablasts. Here, Change at week is represented as CW. | Baseline, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48 | 
| Change From Baseline in Lymphocyte Subsets Counts up to 48 Weeks: Myeloid and Natural Killer (NK) Cells | Myeloid and natural killer cell subsets include CD56Bright NK cells, CD56Dim NK cells, Classical Monocytes, Myeloid dendritic cells, Non-classical Monocytes, Plasmacytoid dendritic cells, Total dendritic cells and Total monocytes [CD14+]. | Baseline, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48 | 
| Change From Baseline in Lymphocyte Subsets Counts up to 48 Weeks: T-Cell Cytokines | T-cell cytokine subsets include IFN (interferon) g+ (% of CD4+ T cells), IFNg+ (% of CD8+ T cells), IFNg+ (% of memory CD4+ T cells), IFNg+ (% of memory CD8+ T cells), IL- (interleukin) 17A+/IFNg- (% of CD4+ T cells), IL-17A+/IFNg- (% of CD8+ T cells), IL-17A+/IFNg- (% of memory CD4+ T cells), IL-17A+/IFNg- (% of memory CD8+ T cells), IL-2+ (% of CD4+ T cells), IL-2+ (% of CD8+ T cells), IL-2+ (% of memory CD4+ T cells), IL-2+ (% of memory CD8+ T cells), IL-4+ (% of CD4+ T cells), IL-4+ (% of CD8+ T cells), IL-4+ (% of memory CD4+ T cells) and IL-4+ (% of memory CD8+ T cells). Here, Change at week is represented as CW. | Baseline, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48 | 
| Change From Baseline in Lymphocyte Subsets Counts up to 48 Weeks: Very Late Antigen-4 (VLA-4/Lymphocyte Function-Associated Antigen-1 (LFA-1) Antigen | VLA-4/LFA-1 antigen subsets include CD11a+ (% of B cells), CD11a+ (% of T cells), CD11a+ (% of MNC), CD11a+ (% of dendritic cells [CD11c++]), CD11a+ (% of lymphocytes), CD11a+ (% of monocytes), CD11a+ (% of neutrophils), CD49d+ (% of B cells), CD49d+ (% of T cells), CD49d+ (% of MNC), CD49d+ (% of dendritic cells [CD11c++]), CD49d+ (% of lymphocytes), CD49d+ (% of monocytes) and CD49d+ (% of neutrophils). | Baseline, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Immunoglobulin A (IgA) up to 48 Weeks |  | Baseline, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48 | 
| Change From Baseline in Immunoglobulin M (IgM) up to 48 Weeks |  | Baseline, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48 | 
| Change From Baseline in Immunoglobulin G (IgG) up to 48 Weeks |  | Baseline, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48 | 
| Change From Baseline in Immunoglobulin G (IgG) Subclasses up to 48 Weeks |  | Baseline, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tecfidera, DMF, dimethyl fumarate