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

Multiple Sclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02525874
• Other study ID #: 109MS310
• Secondary ID: 2015-001973-42
• Status: Completed
• Phase: Phase 3
• Start date: August 11, 2015
• Est. completion date: April 23, 2018

Study information

• Verified date: June 2019
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 218
• Est. completion date: April 23, 2018
• Est. primary completion date: April 24, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Sclerosis

Intervention

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

Locations

Country	Name	City	State
Belgium	Research Site	Brasschaat
Belgium	Research Site	Brugge	West-Vlaanderen
Belgium	Research Site	La Louviere	Hainaut
Bulgaria	Research Site	Plaven
Bulgaria	Research Site	Pleven
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Kuwait	Research Site	Kuwait City
Lithuania	Research Site	Kaunas
Lithuania	Research Site	Klaipeda
Lithuania	Research Site	Vilnius
Poland	Research Site	Bydgoszcz
Poland	Research Site	Katowice
Poland	Research Site	Katowice
Poland	Research Site	Lodz
Poland	Research Site	Plewiska
Poland	Research Site	Szczecin
Turkey	Research Site	Umuttepe	Kocaeli
United States	Research Site	Atlanta	Georgia
United States	Research Site	Baltimore	Maryland
United States	Research Site	Gilbert	Arizona
United States	Research Site	Long Beach	California
United States	Research Site	Ocala	Florida
United States	Research Site	Oldsmar	Florida
United States	Research Site	Overland Park	Kansas
United States	Research Site	Raleigh	North Carolina
United States	Research Site	Salt Lake City	Utah
United States	Research Site	San Antonio	Texas
United States	Research Site	Spartanburg	South Carolina
United States	Research Site	Tacoma	Washington
United States	Research Site	Tampa	Florida
United States	Research Site	Tampa	Florida
United States	Research Site	Traverse City	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Countries where clinical trial is conducted

United States,  Belgium,  Bulgaria,  Kuwait,  Lithuania,  Poland,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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