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

Phase 3

Completed

Conditions: Multiple Sclerosis, Relapsing-Remitting
Multiple Sclerosis

Interventions: Drug: dimethyl fumarate

Registration Number: NCT02525874

Lead Sponsor: Biogen

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 218

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
dimethyl fumarate	dimethyl fumarate	120 mg twice daily (BID) for the first 7 days and 240 mg BID thereafter

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Lymphocyte Subsets Counts up to 48 Weeks: T Cell, B Cell, Natural Killer Cell (TBNK)	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	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	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	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	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	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 Outcome Measures

Name	Time	Method
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