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

NCT02525874 | Completed Phase 3 Results

• 2 other identifiers: 109MS3102015-001973-42
• Study Type: interventional
• Target: 218
• Locations: 7 countries
• Sites: 34

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.

Conditions

Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis

Keywords

Tecfidera; DMF; dimethyl fumarate

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (4)

• 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

Study Arms (1)

dimethyl fumarate

EXPERIMENTAL

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

Drug: dimethyl fumarate

Interventions

dimethyl fumarate DRUG

Initial oral dose for 7 days with maintenance dose thereafter

Also known as: BG00012, Tecfidera, DMF

dimethyl fumarate

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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) \[Polman 2011\]

You may not qualify if:

• 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

Sponsors & Collaborators

• Biogen: lead

Study Sites (34)

Research Site

Gilbert, Arizona, 85234, United States

Location

Research Site

Long Beach, California, 90806, United States

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Ocala, Florida, 34471, United States

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Oldsmar, Florida, 34677, United States

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Tampa, Florida, 33609, United States

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Tampa, Florida, 33612, United States

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Atlanta, Georgia, 30342, United States

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Overland Park, Kansas, 66212, United States

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Baltimore, Maryland, 33612, United States

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Traverse City, Michigan, 49684, United States

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Raleigh, North Carolina, 27607, United States

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Spartanburg, South Carolina, 29307, United States

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San Antonio, Texas, 78258, United States

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Salt Lake City, Utah, 84103, United States

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Tacoma, Washington, 98405, United States

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La Louvière, Hainaut, 7100, Belgium

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Bruges, West-Vlaanderen, 8000, Belgium

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Brasschaat, 2930, Belgium

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Plaven, 5800, Bulgaria

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Pleven, 5800, Bulgaria

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Sofia, 1113, Bulgaria

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Sofia, 1606, Bulgaria

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Sofia, Bulgaria

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Kuwait City, 00001, Kuwait

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Kaunas, LT-50009, Lithuania

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Klaipėda, 92288, Lithuania

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Vilnius, LT-08661, Lithuania

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Bydgoszcz, 85-795, Poland

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Katowice, 40-595, Poland

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Katowice, 40-650, Poland

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Lodz, 90-324, Poland

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Plewiska, 62-064, Poland

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Szczecin, 70-215, Poland

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Umuttepe, Kocaeli, 41380, Turkey (Türkiye)

Location

Related Publications (1)

• Mao-Draayer Y, Bar-Or A, Balashov K, Foley J, Smoot K, Longbrake EE, Robertson D, Mendoza JP, Lewin JB, Everage N, Bozin I, Lyons J, Mokliatchouk O, Bame E, Giuliani F. Real-World Safety and Effectiveness of Dimethyl Fumarate in Patients with MS: Results from the ESTEEM Phase 4 and PROCLAIM Phase 3 Studies with a Focus on Older Patients. Adv Ther. 2025 Jan;42(1):395-412. doi: 10.1007/s12325-024-03047-w. Epub 2024 Nov 21.

  PMID: 39570545 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis

Interventions

Dimethyl Fumarate

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Fumarates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Results Point of Contact

• Title: US Biogen Clinical Trial Center
• Organization: Biogen

clinicaltrials@biogen.com

866-633-4636

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2015
• First Posted: August 18, 2015
• Study Start: August 11, 2015
• Primary Completion: April 24, 2017
• Study Completion: April 23, 2018
• Last Updated: June 27, 2019
• Results First Posted: June 27, 2019

Record last verified: 2019-06

Locations

TU (1); BU (5); LI (3); US (15); PL (6); BE (3); KU (1)