An Open-Label Study to Assess the Effects of BG00012 on Lymphocyte Subsets in Subjects With Relapsing-Remitting Multiple Sclerosis
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Biogen
- Enrollment
- 218
- Locations
- 1
- Primary Endpoint
- Change From Baseline in Lymphocyte Subsets Counts up to 48 Weeks: T Cell, B Cell, Natural Killer Cell (TBNK)
Study Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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]
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
Arms & Interventions
dimethyl fumarate
120 mg twice daily (BID) for the first 7 days and 240 mg BID thereafter
Intervention: dimethyl fumarate (Drug)
Outcomes
Primary Outcomes
Change From Baseline in Lymphocyte Subsets Counts up to 48 Weeks: T Cell, B Cell, Natural Killer Cell (TBNK)
Time Frame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48
Lymphocyte subsets include T cell, B cell and Natural killer (NK) cells.
Change From Baseline in Lymphocyte Subsets Counts up to 48 Weeks: T-Cells Subsets
Time Frame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48
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.
Change From Baseline in Lymphocyte Subsets Counts up to 48 Weeks: B-Cell Subsets
Time Frame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48
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.
Change From Baseline in Lymphocyte Subsets Counts up to 48 Weeks: Myeloid and Natural Killer (NK) Cells
Time Frame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48
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 \[CD14+\].
Change From Baseline in Lymphocyte Subsets Counts up to 48 Weeks: T-Cell Cytokines
Time Frame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48
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.
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
Time Frame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48
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).
Secondary Outcomes
- 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 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 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)