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

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

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 Overview

• Status: Completed
• Conditions: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting
• Intervention / Treatment: Drug: dimethyl fumarate

• Study Type: Interventional
• Enrollment (Actual): 218
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brasschaat, Belgium, 2930
    • Research Site
  • Hainaut
    • La Louviere, Hainaut, Belgium, 7100
      • Research Site
  • West-Vlaanderen
    • Brugge, West-Vlaanderen, Belgium, 8000
      • Research Site
• Bulgaria
  • Plaven, Bulgaria, 5800
    • Research Site
  • Pleven, Bulgaria, 5800
    • Research Site
  • Sofia, Bulgaria
    • Research Site
  • Sofia, Bulgaria, 1606
    • Research Site
  • Sofia, Bulgaria, 1113
    • Research Site
• Kuwait
  • Kuwait City, Kuwait, 00001
    • Research Site
• Lithuania
  • Kaunas, Lithuania, LT-50009
    • Research Site
  • Klaipeda, Lithuania, 92288
    • Research Site
  • Vilnius, Lithuania, LT-08661
    • Research Site
• Poland
  • Bydgoszcz, Poland, 85-795
    • Research Site
  • Katowice, Poland, 40-595
    • Research Site
  • Katowice, Poland, 40-650
    • Research Site
  • Lodz, Poland, 90-324
    • Research Site
  • Plewiska, Poland, 62-064
    • Research Site
  • Szczecin, Poland, 70-215
    • Research Site
• Turkey
  • Kocaeli
    • Umuttepe, Kocaeli, Turkey, 41380
      • Research Site
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Research Site
  • California
    • Long Beach, California, United States, 90806
      • Research Site
  • Florida
    • Ocala, Florida, United States, 34471
      • Research Site
    • Oldsmar, Florida, United States, 34677
      • Research Site
    • Tampa, Florida, United States, 33612
      • Research Site
    • Tampa, Florida, United States, 33609
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Research Site
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 33612
      • Research Site
  • Michigan
    • Traverse City, Michigan, United States, 49684
      • Research Site
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • Research Site
  • South Carolina
    • Spartanburg, South Carolina, United States, 29307
      • Research Site
  • Texas
    • San Antonio, Texas, United States, 78258
      • Research Site
  • Utah
    • Salt Lake City, Utah, United States, 84103
      • Research Site
  • Washington
    • Tacoma, Washington, United States, 98405
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: dimethyl fumarate; 120 mg twice daily (BID) for the first 7 days and 240 mg BID thereafter	Drug: dimethyl fumarate; Initial oral dose for 7 days with maintenance dose thereafter; Other Names: BG00012; DMF; Tecfidera

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Biogen

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2015
• Primary Completion (Actual): April 24, 2017
• Study Completion (Actual): April 23, 2018

Study Registration Dates

• First Submitted: July 10, 2015
• First Submitted That Met QC Criteria: August 14, 2015
• First Posted (Estimate): August 18, 2015

Study Record Updates

• Last Update Posted (Actual): June 27, 2019
• Last Update Submitted That Met QC Criteria: June 10, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Tecfidera; dimethyl fumarate; DMF
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Dimethyl Fumarate
• Other Study ID Numbers: 109MS310; 2015-001973-42 (EudraCT Number)