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

Overview

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.

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

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: April 24, 2017

Interventions

  • Drug: dimethyl fumarate
    • Initial oral dose for 7 days with maintenance dose thereafter

Arms, Groups and Cohorts

  • Experimental: dimethyl fumarate
    • 120 mg twice daily (BID) for the first 7 days and 240 mg BID thereafter

Clinical Trial Outcome Measures

Primary Measures

  • 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 Measures

  • Change From Baseline in Immunoglobulin A (IgA) up to 48 Weeks
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 65 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Biogen
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Medical Director, Study Director, Biogen

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