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

Primary Purpose

Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

dimethyl fumarate

About this trial

This is an interventional treatment trial for Multiple Sclerosis, Relapsing-Remitting focused on measuring Tecfidera, DMF, dimethyl fumarate

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

dimethyl fumarate

Arm Description

120 mg twice daily (BID) for the first 7 days and 240 mg BID thereafter

Outcomes

Primary Outcome Measures

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.

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.

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.

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+].

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.

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).

Secondary Outcome Measures

Change From Baseline in Immunoglobulin A (IgA) up to 48 Weeks

Change From Baseline in Immunoglobulin M (IgM) up to 48 Weeks

Change From Baseline in Immunoglobulin G (IgG) up to 48 Weeks

Change From Baseline in Immunoglobulin G (IgG) Subclasses up to 48 Weeks

Full Information

NCT ID

NCT02525874

First Posted

July 10, 2015

Last Updated

June 10, 2019

Sponsor

Biogen

1. Study Identification

Unique Protocol Identification Number

NCT02525874

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2019

Overall Recruitment Status

Completed

Study Start Date

August 11, 2015 (Actual)

Primary Completion Date

April 24, 2017 (Actual)

Study Completion Date

April 23, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Biogen

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis

Keywords

Tecfidera, DMF, dimethyl fumarate

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

218 (Actual)

8. Arms, Groups, and Interventions

Arm Title

dimethyl fumarate

Arm Type

Experimental

Arm Description

120 mg twice daily (BID) for the first 7 days and 240 mg BID thereafter

Intervention Type

Drug

Intervention Name(s)

dimethyl fumarate

Other Intervention Name(s)

BG00012, Tecfidera, DMF

Intervention Description

Initial oral dose for 7 days with maintenance dose thereafter

Primary Outcome Measure Information:

Title

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

Description

Lymphocyte subsets include T cell, B cell and Natural killer (NK) cells.

Time Frame