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BG00012 Phase 2 Combination Study in Participants With Multiple Sclerosis (EXPLORE)

Primary Purpose

Relapsing-Remitting Multiple Sclerosis, Multiple Sclerosis

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
dimethyl fumarate
Sponsored by
Biogen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsing-Remitting Multiple Sclerosis focused on measuring BG00012, MS, RRMS

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

  • Must have a confirmed diagnosis of relapsing-remitting multiple sclerosis (RRMS) according to McDonald criteria #1-4 (Polman et al, 2005 [Appendix I]), and have a prior brain magnetic resonance imaging (MRI) demonstrating lesion (s) consistent with multiple sclerosis (MS) from any point in time.
  • Must have an Expanded Disability Status Scale (EDSS) between 0.0 and 5.0, inclusive.
  • Must be taking the same dose of a prescribed IFNβ (either Avonex, Betaseron, Rebif) or GA for at least 12 months consecutively at the time of enrollment and remain on this treatment for the duration of the study. Participants receiving Rebif must be prescribed 44 μg by subcutaneous injection three times per week.

Key Exclusion Criteria:

  • Primary progressive, secondary progressive, or progressive relapsing MS (as defined by Polman et al. 2005).
  • Other chronic disease of the immune system, malignancies, acute urologic, or pulmonary disease.
  • Pregnant or nursing women.
  • Participation within 6 months prior to study enrollment in any other drug, biologic, or device study.

NOTE: Other protocol-defined Inclusion/Exclusion criteria may apply.

Sites / Locations

  • Research Site
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Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Glatiramer acetate (GA) and dimethyl fumarate

Interferon beta (IFNβ) and dimethyl fumarate

Arm Description

Participants taking a stable dose of GA for at least 12 months prior to the study remain on that dose throughout the study. Dimethyl fumarate is administered at 120 mg three times a day (TID) on Days 1-7, and 240 mg TID on Day 8 until the end of treatment (approximately 6 months).

Participants taking a stable dose of one of the IFNβ products for at least 12 months prior to the study remain on that product and dose throughout the study. Dimethyl fumarate is administered at 120 mg three times a day (TID) on Days 1-7, and 240 mg TID on Day 8 until the end of treatment (approximately 6 months).

Outcomes

Primary Outcome Measures

Summary of Treatment-emergent Adverse Events (TEAEs) Occurring Post-BG00012 Dosing (Add-on Therapy Period)
An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug, whether or not related to the study drug. A serious adverse event (SAE) was any untoward medical occurrence that, at any dose: resulted in death; in the view of the Investigator, placed the participant at immediate risk of death (a life-threatening event); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; was any other medically important event that, in the opinion of the Investigator, jeopardized the participant or required intervention to prevent one of the other outcomes above. TEAE was defined as having an onset date that was on or after the start of study treatment (BG00012), or that worsened after the start of study treatment.
Potentially Clinically Significant Hematology Laboratory Abnormalities for Combination Therapy
Percentage of participants with potentially clinically significant hematology laboratory abnormalities.
Maximum Post-Baseline Values: Liver Enzymes for Combination Therapy
Percentage of participants with post-baseline liver enzyme values above the upper limit of normal (ULN). Liver enzymes included alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), and bilirubin. Elevated ALT/AST (ALT/AST ≥ 3*ULN) concurrent with elevated total bilirubin was also evaluated.
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy
Percentage of participants with post-baseline values for selected urinalysis parameters requiring further evaluation. For urine microscopy, results were categorized for male and female participants. For males, normal/negative was considered 0 to 3 red blood cells/high-power field (rbc/hpf), and positive was categorized in the following stages: 4 to 10, 11 to 20, 21 to 149, and ≥ 150 rbc/hpf. For females, normal/negative was considered 0 to 8 rbc/hpf, and positive was categorized in the following stages: 9 to 20, 21 to 30, 31 to 149, and ≥ 150 rbc/hpf.

Secondary Outcome Measures

Full Information

First Posted
July 1, 2010
Last Updated
February 14, 2017
Sponsor
Biogen
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1. Study Identification

Unique Protocol Identification Number
NCT01156311
Brief Title
BG00012 Phase 2 Combination Study in Participants With Multiple Sclerosis
Acronym
EXPLORE
Official Title
An Open-Label, Multicenter Study in Subjects With Relapsing-Remitting Multiple Sclerosis to Evaluate the Safety of 240 mg BG00012 TID Administered as Add-On Therapy to Beta Interferons (IFNβ) or Glatiramer Acetate (GA)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
June 2010 (undefined)
Primary Completion Date
March 2012 (Actual)
Study Completion Date
March 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biogen

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The primary objective of the study is to evaluate the safety and tolerability of BG00012 (dimethyl fumarate) administered in combination with interferon b (IFNß) or glatiramer acetate (GA) in participants with relapsing-remitting multiple sclerosis (RRMS).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsing-Remitting Multiple Sclerosis, Multiple Sclerosis
Keywords
BG00012, MS, RRMS

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
108 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Glatiramer acetate (GA) and dimethyl fumarate
Arm Type
Experimental
Arm Description
Participants taking a stable dose of GA for at least 12 months prior to the study remain on that dose throughout the study. Dimethyl fumarate is administered at 120 mg three times a day (TID) on Days 1-7, and 240 mg TID on Day 8 until the end of treatment (approximately 6 months).
Arm Title
Interferon beta (IFNβ) and dimethyl fumarate
Arm Type
Experimental
Arm Description
Participants taking a stable dose of one of the IFNβ products for at least 12 months prior to the study remain on that product and dose throughout the study. Dimethyl fumarate is administered at 120 mg three times a day (TID) on Days 1-7, and 240 mg TID on Day 8 until the end of treatment (approximately 6 months).
Intervention Type
Drug
Intervention Name(s)
dimethyl fumarate
Other Intervention Name(s)
Tecfidera, DMF, BG00012
Intervention Description
Days 1-7: 120 mg three times a day (TID) for a total daily dose of 360 mg. Day 8 to Week 24: 240 mg TID for a total daily dose of 720 mg. Drug supplied as a capsule taken orally.
Primary Outcome Measure Information:
Title
Summary of Treatment-emergent Adverse Events (TEAEs) Occurring Post-BG00012 Dosing (Add-on Therapy Period)
Description
An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug, whether or not related to the study drug. A serious adverse event (SAE) was any untoward medical occurrence that, at any dose: resulted in death; in the view of the Investigator, placed the participant at immediate risk of death (a life-threatening event); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; was any other medically important event that, in the opinion of the Investigator, jeopardized the participant or required intervention to prevent one of the other outcomes above. TEAE was defined as having an onset date that was on or after the start of study treatment (BG00012), or that worsened after the start of study treatment.
Time Frame
AEs were collected from enrollment until the final study visit (Week 26 +/-5 days).
Title
Potentially Clinically Significant Hematology Laboratory Abnormalities for Combination Therapy
Description
Percentage of participants with potentially clinically significant hematology laboratory abnormalities.
Time Frame
collected from the start of BG00012 administration through to Week 26 +/- 5 days
Title
Maximum Post-Baseline Values: Liver Enzymes for Combination Therapy
Description
Percentage of participants with post-baseline liver enzyme values above the upper limit of normal (ULN). Liver enzymes included alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), and bilirubin. Elevated ALT/AST (ALT/AST ≥ 3*ULN) concurrent with elevated total bilirubin was also evaluated.
Time Frame
collected from the start of BG00012 administration through to Week 26 +/- 5 days
Title
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy
Description
Percentage of participants with post-baseline values for selected urinalysis parameters requiring further evaluation. For urine microscopy, results were categorized for male and female participants. For males, normal/negative was considered 0 to 3 red blood cells/high-power field (rbc/hpf), and positive was categorized in the following stages: 4 to 10, 11 to 20, 21 to 149, and ≥ 150 rbc/hpf. For females, normal/negative was considered 0 to 8 rbc/hpf, and positive was categorized in the following stages: 9 to 20, 21 to 30, 31 to 149, and ≥ 150 rbc/hpf.
Time Frame
collected from the start of BG00012 administration through to Week 26 +/- 5 days
Other Pre-specified Outcome Measures:
Title
Summary of Adverse Events (AEs) Occurring Before BG00012 Dosing (Monotherapy Period)
Description
Percentage of participants with AEs, serious AEs (SAEs), and discontinuations due to AEs. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug, whether or not related to the study drug. An SAE was any untoward medical occurrence that, at any dose: resulted in death; in the view of the Investigator, placed the participant at immediate risk of death (a life-threatening event); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; was any other medically important event that, in the opinion of the Investigator, jeopardized the participant or required intervention to prevent one of the other outcomes above. AEs were categorized as mild, moderate, or severe. All AEs occurring from enrollment to the day before BG00012 dosing are included.
Time Frame
from time of enrollment until day before first administration of BG00012 (Week -8 to Week 0)
Title
Average Number of Gadolinium (Gd)-Enhancing Lesions: Week -8, -4, 0 Average Versus Week 16, 20, 24 Average
Description
The average is calculated as (total number of lesions in non-missing scans / number of non-missing magnetic resonance imaging [MRI] scans).
Time Frame
Week -8 through Week 24
Title
Average Number of New Gd-Enhancing Lesions: Weeks -4, 0 Average Versus Weeks 20, 24 Average
Description
The average is calculated as (total number of lesions in non-missing scans / number of non-missing MRI scans).
Time Frame
Week -4 through Week 24
Title
Number of New or Newly Enlarging T2 Lesions
Description
The number of new T2 lesions divided by the number of months since the reference visit during the Monotherapy Period and the Add-On Therapy Period.
Time Frame
Week -8 to Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Must have a confirmed diagnosis of relapsing-remitting multiple sclerosis (RRMS) according to McDonald criteria #1-4 (Polman et al, 2005 [Appendix I]), and have a prior brain magnetic resonance imaging (MRI) demonstrating lesion (s) consistent with multiple sclerosis (MS) from any point in time. Must have an Expanded Disability Status Scale (EDSS) between 0.0 and 5.0, inclusive. Must be taking the same dose of a prescribed IFNβ (either Avonex, Betaseron, Rebif) or GA for at least 12 months consecutively at the time of enrollment and remain on this treatment for the duration of the study. Participants receiving Rebif must be prescribed 44 μg by subcutaneous injection three times per week. Key Exclusion Criteria: Primary progressive, secondary progressive, or progressive relapsing MS (as defined by Polman et al. 2005). Other chronic disease of the immune system, malignancies, acute urologic, or pulmonary disease. Pregnant or nursing women. Participation within 6 months prior to study enrollment in any other drug, biologic, or device study. NOTE: Other protocol-defined Inclusion/Exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Biogen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Gilbert
State/Province
Arizona
Country
United States
Facility Name
Research Site
City
Phoenix
State/Province
Arizona
Country
United States
Facility Name
Research Site
City
Danbury
State/Province
Connecticut
Country
United States
Facility Name
Research Site
City
Atlanta
State/Province
Georgia
Country
United States
Facility Name
Research Site
City
Fort Wayne
State/Province
Indiana
Country
United States
Facility Name
Research Site
City
Baltimore
State/Province
Maryland
Country
United States
Facility Name
Research Site
City
Boston
State/Province
Massachusetts
Country
United States
Facility Name
Research Site
City
Golden Valley
State/Province
Minnesota
Country
United States
Facility Name
Research Site
City
Teaneck
State/Province
New Jersey
Country
United States
Facility Name
Research Site
City
Patchogue
State/Province
New York
Country
United States
Facility Name
Research Site
City
Cleveland
State/Province
Ohio
Country
United States
Facility Name
Research Site
City
Dayton
State/Province
Ohio
Country
United States
Facility Name
Research Site
City
Portland
State/Province
Oregon
Country
United States
Facility Name
Research Site
City
Cordova
State/Province
Tennessee
Country
United States
Facility Name
Research Site
City
Franklin
State/Province
Tennessee
Country
United States
Facility Name
Research Site
City
Milwaukee
State/Province
Wisconsin
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
27252601
Citation
Calkwood J, Vollmer T, Fox RJ, Zhang R, Novas M, Sheikh SI, Viglietta V. Safety and Tolerability of Delayed-Release Dimethyl Fumarate Administered with Interferon Beta or Glatiramer Acetate in Relapsing-Remitting Multiple Sclerosis. Int J MS Care. 2016 May-Jun;18(3):138-46. doi: 10.7224/1537-2073.2015-020.
Results Reference
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BG00012 Phase 2 Combination Study in Participants With Multiple Sclerosis

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