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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01156311
Recruitment Status : Completed
First Posted : July 2, 2010
Results First Posted : June 9, 2015
Last Update Posted : March 21, 2017
Sponsor:
Information provided by (Responsible Party):
Biogen

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Relapsing-Remitting Multiple Sclerosis
Multiple Sclerosis
Intervention Drug: dimethyl fumarate
Enrollment 108
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Monotherapy Period: Interferon Beta (IFNß) Monotherapy Period: Glatiramer Acetate (GA) Add-on Therapy Period: Dimethyl Fumarate Add-on to IFNß Add-on Therapy Period: Dimethyl Fumarate Add-on to GA
Hide Arm/Group Description Participants taking a stable dose of one of the IFNß products for at least 12 months prior to the study remained on that product and dose throughout the study. The monotherapy period included the 8 weeks prior to the first dose of dimethyl fumarate. Participants taking a stable dose of GA for at least 12 months prior to the study remained on that dose throughout the study. The monotherapy period included the 8 weeks prior to the first dose of dimethyl fumarate.

BG00012 (dimethyl fumarate) was to be 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) as an add-on to a stable dose of IFNß.

Participants taking a stable dose of one of the IFNß products for at least 12 months prior to the study remained on that product and dose throughout the study.

Dimethyl fumarate was to be administered at 120 mg 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 GA for at least 12 months prior to the study remained on that dose throughout the study.

Period Title: 2-Month Monotherapy Period
Started 59 49 0 0
Completed 57 47 0 0
Not Completed 2 2 0 0
Reason Not Completed
Withdrawal by Subject             1             1             0             0
Physician Decision             0             1             0             0
Not specified             1             0             0             0
Period Title: 6-month Add-on Therapy Period
Started 0 0 57 47
Completed BG00012 Combination Therapy 0 0 45 38
Completed 0 0 45 37
Not Completed 0 0 12 10
Reason Not Completed
Adverse Event             0             0             7             6
Lost to Follow-up             0             0             2             0
Disease Activity             0             0             1             2
Physician Decision             0             0             1             0
Not Specified             0             0             1             2
Arm/Group Title Interferon Beta (IFNß) and BG00012 (Dimethyl Fumarate) Glatiramer Acetate (GA) and BG00012 (Dimethyl Fumarate) Total
Hide Arm/Group Description Participants taking a stable dose of one of the IFNß products for at least 12 months prior to the study remained on that product and dose throughout the study. BG00012 (dimethyl fumarate) was to be administered at 120 mg 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 GA for at least 12 months prior to the study remained on that dose throughout the study. BG00012 (dimethyl fumarate) was to be administered at 120 mg TID on Days 1-7, and 240 mg TID on Day 8 until the end of treatment (approximately 6 months). Total of all reporting groups
Overall Number of Baseline Participants 57 47 104
Hide Baseline Analysis Population Description
Intent-to-Treat (ITT) Population: participants who took at least 1 capsule of BG00012 concurrently with the background therapy (combination therapy).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 57 participants 47 participants 104 participants
39.5  (7.58) 40.7  (8.44) 40.1  (7.96)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 57 participants 47 participants 104 participants
18 to 19 years 1 0 1
20 to 29 years 5 3 8
30 to 39 years 18 22 40
40 to 49 years 27 15 42
50 to 55 years 6 7 13
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 57 participants 47 participants 104 participants
Female
40
  70.2%
29
  61.7%
69
  66.3%
Male
17
  29.8%
18
  38.3%
35
  33.7%
1.Primary Outcome
Title Summary of Treatment-emergent Adverse Events (TEAEs) Occurring Post-BG00012 Dosing (Add-on Therapy Period)
Hide 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).
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Population for the Combination Therapy Period was defined as any participant who took at least 1 capsule of BG00012 concurrently with the background therapy.
Arm/Group Title Interferon Beta (IFNß) and BG00012 (Dimethyl Fumarate) Glatiramer Acetate (GA) and BG00012 (Dimethyl Fumarate)
Hide Arm/Group Description:
Participants taking a stable dose of one of the IFNß products for at least 12 months prior to the study remained on that product and dose throughout the study. BG00012 (dimethyl fumarate) was to be administered at 120 mg 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 GA for at least 12 months prior to the study remained on that dose throughout the study. BG00012 (dimethyl fumarate) was to be administered at 120 mg TID on Days 1-7, and 240 mg TID on Day 8 until the end of treatment (approximately 6 months).
Overall Number of Participants Analyzed 57 47
Measure Type: Number
Unit of Measure: percentage of participants
Participants with a TEAE 95 100
Participants with a moderate or severe TEAE 72 70
Participants with a severe TEAE 14 15
Participants with a related TEAE 74 87
Participants with a serious TEAE 4 2
Participants discontinuing BG00012 due to a TEAE 14 17
Participants withdrawing from study due to a TEAE 14 17
2.Primary Outcome
Title Potentially Clinically Significant Hematology Laboratory Abnormalities for Combination Therapy
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the safety population with at least one post-baseline value. Safety Population for the Combination Therapy Period was defined as any participant who took at least 1 capsule of BG00012 concurrently with the background therapy.
Arm/Group Title Interferon Beta (IFNß) and BG00012 (Dimethyl Fumarate) Glatiramer Acetate (GA) and BG00012 (Dimethyl Fumarate)
Hide Arm/Group Description:
Participants taking a stable dose of one of the IFNß products for at least 12 months prior to the study remained on that product and dose throughout the study. BG00012 (dimethyl fumarate) was to be administered at 120 mg 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 GA for at least 12 months prior to the study remained on that dose throughout the study. BG00012 (dimethyl fumarate) was to be administered at 120 mg TID on Days 1-7, and 240 mg TID on Day 8 until the end of treatment (approximately 6 months).
Overall Number of Participants Analyzed 56 47
Measure Type: Number
Unit of Measure: percentage of participants
White Blood Cells (total) < 3.0*10^9/L 9 2
White Blood Cells (total) ≥ 16*10^9/L 2 2
Lymphocytes < 0.8*10^9/L 32 6
Lymphocytes < 0.5*10^9/L 7 4
Lymphocytes > 12*10^9/L 0 0
Neutrophils ≤ 1.0*10^9/L 0 0
Neutrophils < 1.5*10^9/L 13 2
Neutrophils ≥ 12*10^9/L 2 4
Red Blood Cells ≤ 3.3*10^12/L 0 0
Red Blood Cells ≥ 6.8*10^12/L 0 0
Hemoglobin g/L ≤ 100 0 0
Platelet Count ≤ 100*10^9/L 0 0
Platelet Count ≥ 600*10^9/L 0 0
3.Primary Outcome
Title Maximum Post-Baseline Values: Liver Enzymes for Combination Therapy
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the safety population with at least one post-baseline value. Safety Population for the Combination Therapy Period was defined as any participant who took at least 1 capsule of BG00012 concurrently with the background therapy.
Arm/Group Title Interferon Beta (IFNß) and BG00012 (Dimethyl Fumarate) Glatiramer Acetate (GA) and BG00012 (Dimethyl Fumarate)
Hide Arm/Group Description:
Participants taking a stable dose of one of the IFNß products for at least 12 months prior to the study remained on that product and dose throughout the study. BG00012 (dimethyl fumarate) was to be administered at 120 mg 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 GA for at least 12 months prior to the study remained on that dose throughout the study. BG00012 (dimethyl fumarate) was to be administered at 120 mg TID on Days 1-7, and 240 mg TID on Day 8 until the end of treatment (approximately 6 months).
Overall Number of Participants Analyzed 57 47
Measure Type: Number
Unit of Measure: percentage of participants
ALT ≤ 1*ULN 47 47
ALT > 1*ULN 53 53
ALT ≥ 3*ULN 5 2
ALT > 5*ULN 2 0
ALT > 10*ULN 0 0
ALT > 20*ULN 0 0
AST ≤ 1*ULN 68 64
AST > 1*ULN 32 36
AST ≥ 3*ULN 2 0
AST > 5*ULN 0 0
AST > 10*ULN 0 0
AST > 20*ULN 0 0
GGT ≤ 1*ULN 72 85
GGT > 1*ULN 28 15
GGT ≥ 3*ULN 4 0
GGT > 5*ULN 2 0
GGT > 10*ULN 0 0
GGT > 20*ULN 0 0
Total Bilirubin ≤ 1*ULN 98 94
Total Bilirubin > 1*ULN 2 6
Total Bilirubin > 1.5*ULN 0 4
Total Bilirubin > 2*ULN 0 2
ALT/AST ≥ 3*ULN + Total Bilirubin > 1.5*ULN 0 0
ALT/AST ≥ 3*ULN + Total Bilirubin > 2*ULN 0 0
4.Primary Outcome
Title Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Population for the Combination Therapy Period was defined as any participant who took at least 1 capsule of BG00012 concurrently with the background therapy; n=participants in the safety population with at least 1 post-baseline value.
Arm/Group Title Interferon Beta (IFNß) and BG00012 (Dimethyl Fumarate) Glatiramer Acetate (GA) and BG00012 (Dimethyl Fumarate)
Hide Arm/Group Description:
Participants taking a stable dose of one of the IFNß products for at least 12 months prior to the study remained on that product and dose throughout the study. BG00012 (dimethyl fumarate) was to be administered at 120 mg 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 GA for at least 12 months prior to the study remained on that dose throughout the study. BG00012 (dimethyl fumarate) was to be administered at 120 mg TID on Days 1-7, and 240 mg TID on Day 8 until the end of treatment (approximately 6 months).
Overall Number of Participants Analyzed 57 47
Measure Type: Number
Unit of Measure: percentage of participants
Urine blood: normal/negative; n=57, 47 75 64
Urine blood: trace; n=57, 47 7 9
Urine blood: 1+; n=57, 47 5 15
Urine blood: 2+; n=57, 47 7 11
Urine blood: 3+; n=57, 47 5 2
Urine protein: normal/negative; n=57, 47 39 38
Urine protein: trace; n=57, 47 35 45
Urine protein: 1+; n=57, 47 26 15
Urine protein: 2+; n=57, 47 0 2
Urine protein: 3+; n=57, 47 0 0
Urine protein: 4+; n=57, 47 0 0
Urine glucose: normal/negative; n=57, 47 93 94
Urine glucose: trace; n=57, 47 2 0
Urine glucose: 1+; n=57, 47 2 2
Urine glucose: 2+; n=57, 47 0 4
Urine glucose: 3+; n=57, 47 2 0
Urine glucose: 4+; n=57, 47 2 0
Urine ketone: normal/negative; n=57, 47 47 57
Urine ketone: trace; n=57, 47 9 11
Urine ketone: 1+; n=57, 47 26 28
Urine ketone: 2+; n=57, 47 11 4
Urine ketone: 3+; n=57, 47 4 0
Urine ketone: 4+; n=57, 47 4 0
Urine microscopy (male): 0-3 rbc/hpf; n=9, 16 100 75
Urine microscopy (male): 4-10 rbc/hpf; n=9, 16 0 6
Urine microscopy (male): 11-20 rbc/hpf; n=9, 16 0 13
Urine microscopy (male): 21-149 rbc/hpf; n=9, 16 0 6
Urine microscopy (male): ≥ 150 rbc/hpf; n=9, 16 0 0
Urine microscopy (female): 0-8 rbc/hpf; n=25, 28 76 86
Urine microscopy (female): 9-20 rbc/hpf; n=25, 28 8 4
Urine microscopy (female): 21-30 rbc/hpf; n=25, 28 4 0
Urine microscopy (female): 31-149 rbc/hpf;n=25, 28 0 7
Urine microscopy (female): ≥150 rbc/hpf; n=25, 28 12 4
5.Other Pre-specified Outcome
Title Summary of Adverse Events (AEs) Occurring Before BG00012 Dosing (Monotherapy Period)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Population for the Monotherapy Period was defined as any participant who took at least 1 dose of background therapy.
Arm/Group Title Monotherapy Period: IFNß Monotherapy Period: GA
Hide Arm/Group Description:
Participants taking a stable dose of one of the IFNß products for at least 12 months prior to the study remained on that product and dose throughout the study. The monotherapy period included the 8 weeks prior to the first dose of dimethyl fumarate.
Participants taking a stable dose of GA for at least 12 months prior to the study remained on that dose throughout the study. The monotherapy period included the 8 weeks prior to the first dose of dimethyl fumarate.
Overall Number of Participants Analyzed 59 49
Measure Type: Number
Unit of Measure: percentage of participants
Participants with an AE 56 49
Participants with a moderate or severe AE 22 27
Participants with a severe AE 3 0
Participants with an SAE 0 0
Participants withdrawing from study due to an AE 0 0
6.Other Pre-specified Outcome
Title Average Number of Gadolinium (Gd)-Enhancing Lesions: Week -8, -4, 0 Average Versus Week 16, 20, 24 Average
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Gd cohort: BG00012-dosed participants with at least 1 Gd-enhancing lesion in any 1 of the 3 scans (Weeks -8, -4, or 0) during the Monotherapy Period.
Arm/Group Title Interferon Beta (IFNß) and BG00012 (Dimethyl Fumarate) Glatiramer Acetate (GA) and BG00012 (Dimethyl Fumarate)
Hide Arm/Group Description:
Participants taking a stable dose of one of the IFNß products for at least 12 months prior to the study remained on that product and dose throughout the study. BG00012 (dimethyl fumarate) was to be administered at 120 mg 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 GA for at least 12 months prior to the study remained on that dose throughout the study. BG00012 (dimethyl fumarate) was to be administered at 120 mg TID on Days 1-7, and 240 mg TID on Day 8 until the end of treatment (approximately 6 months).
Overall Number of Participants Analyzed 16 18
Mean (Standard Deviation)
Unit of Measure: lesions
Average number of lesions from Weeks -8, -4, 0 1.06  (1.011) 1.72  (1.098)
Average number of lesions from Weeks 16, 20, 24 0.17  (0.243) 0.83  (2.115)
Change from average of Weeks -8, -4, 0 -0.90  (0.902) -0.89  (2.264)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Beta (IFNß) and BG00012 (Dimethyl Fumarate)
Comments Change from average of Weeks -8, -4, and 0 to average of Weeks 16, 20, 24 MRI scans.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Wilcoxon signed rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -0.92
Confidence Interval (2-Sided) 95%
-1.17 to -0.33
Estimation Comments based on Hodges-Lehmann estimate
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Glatiramer Acetate (GA) and BG00012 (Dimethyl Fumarate)
Comments Change from average of Weeks -8, -4, and 0 to average of Weeks 16, 20, 24 MRI scans.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0124
Comments [Not Specified]
Method Wilcoxon signed rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -1.17
Confidence Interval (2-Sided) 95%
-1.83 to -0.33
Estimation Comments based on Hodges-Lehmann estimate
7.Other Pre-specified Outcome
Title Average Number of New Gd-Enhancing Lesions: Weeks -4, 0 Average Versus Weeks 20, 24 Average
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Gd cohort: BG00012-dosed participants with at least 1 Gd-enhancing lesion in any 1 of the 3 scans (Weeks -8, -4, or 0) during the Monotherapy Period.
Arm/Group Title Interferon Beta (IFNß) and BG00012 (Dimethyl Fumarate) Glatiramer Acetate (GA) and BG00012 (Dimethyl Fumarate)
Hide Arm/Group Description:
Participants taking a stable dose of one of the IFNß products for at least 12 months prior to the study remained on that product and dose throughout the study. BG00012 (dimethyl fumarate) was to be administered at 120 mg 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 GA for at least 12 months prior to the study remained on that dose throughout the study. BG00012 (dimethyl fumarate) was to be administered at 120 mg TID on Days 1-7, and 240 mg TID on Day 8 until the end of treatment (approximately 6 months).
Overall Number of Participants Analyzed 16 17
Mean (Standard Deviation)
Unit of Measure: lesions
Average number of lesions from Weeks -4, 0 0.91  (0.953) 0.79  (0.985)
Average number of lesions from Weeks 20, 24 0.06  (0.171) 0.18  (0.303)
Change from average of Weeks -4, 0 -0.84  (0.978) -0.62  (1.054)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Beta (IFNß) and BG00012 (Dimethyl Fumarate)
Comments Change from average of Weeks -4, and 0 to average of Weeks 20, 24 MRI scans.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0010
Comments [Not Specified]
Method Wilcoxon signed rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -0.50
Confidence Interval (2-Sided) 95%
-1.50 to -0.25
Estimation Comments based on Hodges-Lehmann estimate
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Glatiramer Acetate (GA) and BG00012 (Dimethyl Fumarate)
Comments Change from average of Weeks -4, and 0 to average of Weeks 20, 24 MRI scans.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0339
Comments [Not Specified]
Method Wilcoxon signed rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -0.50
Confidence Interval (2-Sided) 95%
-1.25 to 0.00
Estimation Comments based on Hodges-Lehmann estimate
8.Other Pre-specified Outcome
Title Number of New or Newly Enlarging T2 Lesions
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Number of participants in the Gd cohort with analyzable data in both Monotherapy and Add-on Therapy Periods. Gd cohort: BG00012-dosed participants with at least 1 Gd-enhancing lesion in any 1 of the 3 scans (Weeks -8, -4, or 0) during the Monotherapy Period.
Arm/Group Title Interferon Beta 1a (IFNß) and BG00012 (Dimethyl Fumarate) Glatiramer Acetate (GA) and BG00012 (Dimethyl Fumarate)
Hide Arm/Group Description:
Participants taking a stable dose of one of the IFNß products for at least 12 months prior to the study remained on that product and dose throughout the study. BG00012 (dimethyl fumarate) was to be administered at 120 mg 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 GA for at least 12 months prior to the study remained on that dose throughout the study. BG00012 (dimethyl fumarate) was to be administered at 120 mg TID on Days 1-7, and 240 mg TID on Day 8 until the end of treatment (approximately 6 months).
Overall Number of Participants Analyzed 15 18
Mean (Standard Deviation)
Unit of Measure: lesions per month
New lesions in the Monotherapy Period 1.23  (1.498) 0.89  (1.243)
New lesions in the Add-on Therapy Period 0.67  (1.257) 0.25  (0.293)
Time Frame AEs for the Monotherapy Period collected from enrollment until prior to administration of BG00012. TEAEs for the Add-on Therapy Period collected from start of BG00012 until the final study visit (Week 26 +/-5 days).
Adverse Event Reporting Description AEs for the Monotherapy Period were summarized for all enrolled participants and were included for completeness only. No direct comparisons were made between the 2-month Monotherapy and the 6-month Add-on Therapy Periods due to the difference in the length of observation between these 2 periods.
 
Arm/Group Title Monotherapy Period: IFNß Monotherapy Period: GA Add-on Therapy Period: IFNß and BG00012 Add-on Therapy Period: GA and BG00012
Hide Arm/Group Description A stable dose of one of the IFNß products for up to 8 weeks (until the first dose of BG00012). A stable dose of GA for up to 8 weeks (until the first dose of BG00012). Participants taking a stable dose of one of the IFNß products for at least 12 months prior to the study remained on that product and dose throughout the study. BG00012 (dimethyl fumarate) was to be administered at 120 mg 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 GA for at least 12 months prior to the study remained on that dose throughout the study. BG00012 (dimethyl fumarate) was to be administered at 120 mg TID on Days 1-7, and 240 mg TID on Day 8 until the end of treatment (approximately 6 months).
All-Cause Mortality
Monotherapy Period: IFNß Monotherapy Period: GA Add-on Therapy Period: IFNß and BG00012 Add-on Therapy Period: GA and BG00012
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Monotherapy Period: IFNß Monotherapy Period: GA Add-on Therapy Period: IFNß and BG00012 Add-on Therapy Period: GA and BG00012
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/59 (0.00%)   0/49 (0.00%)   2/57 (3.51%)   1/47 (2.13%) 
Gastrointestinal disorders         
Abdominal pain upper  1  0/59 (0.00%)  0/49 (0.00%)  1/57 (1.75%)  0/47 (0.00%) 
Gastrointestinal pain  1  0/59 (0.00%)  0/49 (0.00%)  1/57 (1.75%)  0/47 (0.00%) 
Infections and infestations         
Clostridial infection  1  0/59 (0.00%)  0/49 (0.00%)  0/57 (0.00%)  1/47 (2.13%) 
Metabolism and nutrition disorders         
Diabetes mellitus  1  0/59 (0.00%)  0/49 (0.00%)  1/57 (1.75%)  0/47 (0.00%) 
Musculoskeletal and connective tissue disorders         
Muscular weakness  1  0/59 (0.00%)  0/49 (0.00%)  1/57 (1.75%)  0/47 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Monotherapy Period: IFNß Monotherapy Period: GA Add-on Therapy Period: IFNß and BG00012 Add-on Therapy Period: GA and BG00012
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   13/59 (22.03%)   7/49 (14.29%)   53/57 (92.98%)   45/47 (95.74%) 
Cardiac disorders         
Palpitations  1  0/59 (0.00%)  0/49 (0.00%)  3/57 (5.26%)  1/47 (2.13%) 
Gastrointestinal disorders         
Diarrhoea  1  0/59 (0.00%)  0/49 (0.00%)  18/57 (31.58%)  7/47 (14.89%) 
Abdominal Pain  1  0/59 (0.00%)  0/49 (0.00%)  12/57 (21.05%)  3/47 (6.38%) 
Nausea  1  0/59 (0.00%)  0/49 (0.00%)  11/57 (19.30%)  4/47 (8.51%) 
Abdominal Pain Upper  1  0/59 (0.00%)  0/49 (0.00%)  8/57 (14.04%)  4/47 (8.51%) 
Abdominal Discomfort  1  0/59 (0.00%)  0/49 (0.00%)  7/57 (12.28%)  4/47 (8.51%) 
Flatulence  1  0/59 (0.00%)  0/49 (0.00%)  4/57 (7.02%)  6/47 (12.77%) 
Abdominal Distension  1  0/59 (0.00%)  0/49 (0.00%)  4/57 (7.02%)  5/47 (10.64%) 
Constipation  1  0/59 (0.00%)  0/49 (0.00%)  5/57 (8.77%)  2/47 (4.26%) 
Vomiting  1  0/59 (0.00%)  0/49 (0.00%)  5/57 (8.77%)  2/47 (4.26%) 
General disorders         
Fatigue  1  0/59 (0.00%)  0/49 (0.00%)  8/57 (14.04%)  4/47 (8.51%) 
Pyrexia  1  0/59 (0.00%)  0/49 (0.00%)  5/57 (8.77%)  1/47 (2.13%) 
Pain  1  0/59 (0.00%)  0/49 (0.00%)  3/57 (5.26%)  2/47 (4.26%) 
Chills  1  0/59 (0.00%)  0/49 (0.00%)  4/57 (7.02%)  0/47 (0.00%) 
Infections and infestations         
Urinary Tract Infection  1  3/59 (5.08%)  4/49 (8.16%)  2/57 (3.51%)  7/47 (14.89%) 
Nasopharyngitis  1  3/59 (5.08%)  1/49 (2.04%)  8/57 (14.04%)  7/47 (14.89%) 
Upper Respiratory Tract Infection  1  0/59 (0.00%)  0/49 (0.00%)  7/57 (12.28%)  6/47 (12.77%) 
Sinusitis  1  0/59 (0.00%)  0/49 (0.00%)  4/57 (7.02%)  6/47 (12.77%) 
Ear Infection  1  0/59 (0.00%)  0/49 (0.00%)  3/57 (5.26%)  3/47 (6.38%) 
Investigations         
Alanine Aminotransferase Increased  1  0/59 (0.00%)  0/49 (0.00%)  6/57 (10.53%)  7/47 (14.89%) 
Aspartate Aminotransferase Increased  1  0/59 (0.00%)  0/49 (0.00%)  4/57 (7.02%)  4/47 (8.51%) 
Gamma-glutamyltransferase Increased  1  0/59 (0.00%)  0/49 (0.00%)  2/57 (3.51%)  3/47 (6.38%) 
White Blood Cell Count Decreased  1  0/59 (0.00%)  0/49 (0.00%)  5/57 (8.77%)  0/47 (0.00%) 
Neutrophil Count Decreased  1  0/59 (0.00%)  0/49 (0.00%)  3/57 (5.26%)  1/47 (2.13%) 
Lymphocyte Count Decreased  1  0/59 (0.00%)  0/49 (0.00%)  3/57 (5.26%)  0/47 (0.00%) 
Metabolism and nutrition disorders         
Decreased Appetite  1  0/59 (0.00%)  0/49 (0.00%)  4/57 (7.02%)  0/47 (0.00%) 
Musculoskeletal and connective tissue disorders         
Muscle Spasms  1  0/59 (0.00%)  0/49 (0.00%)  6/57 (10.53%)  1/47 (2.13%) 
Pain In Extremity  1  0/59 (0.00%)  0/49 (0.00%)  5/57 (8.77%)  1/47 (2.13%) 
Muscular Weakness  1  0/59 (0.00%)  0/49 (0.00%)  3/57 (5.26%)  2/47 (4.26%) 
Nervous system disorders         
Multiple Sclerosis Relapse  1  8/59 (13.56%)  2/49 (4.08%)  10/57 (17.54%)  7/47 (14.89%) 
Headache  1  0/59 (0.00%)  0/49 (0.00%)  9/57 (15.79%)  7/47 (14.89%) 
Dizziness  1  0/59 (0.00%)  0/49 (0.00%)  8/57 (14.04%)  3/47 (6.38%) 
Hypoaesthesia  1  0/59 (0.00%)  0/49 (0.00%)  4/57 (7.02%)  3/47 (6.38%) 
Balance Disorder  1  0/59 (0.00%)  0/49 (0.00%)  4/57 (7.02%)  2/47 (4.26%) 
Migraine  1  0/59 (0.00%)  0/49 (0.00%)  2/57 (3.51%)  4/47 (8.51%) 
Paraesthesia  1  0/59 (0.00%)  0/49 (0.00%)  3/57 (5.26%)  1/47 (2.13%) 
Decreased Vibratory Sense  1  0/59 (0.00%)  0/49 (0.00%)  3/57 (5.26%)  0/47 (0.00%) 
Psychiatric disorders         
Anxiety  1  0/59 (0.00%)  0/49 (0.00%)  4/57 (7.02%)  0/47 (0.00%) 
Insomnia  1  0/59 (0.00%)  0/49 (0.00%)  3/57 (5.26%)  0/47 (0.00%) 
Skin and subcutaneous tissue disorders         
Rash  1  0/59 (0.00%)  0/49 (0.00%)  3/57 (5.26%)  3/47 (6.38%) 
Pruritus  1  0/59 (0.00%)  0/49 (0.00%)  1/57 (1.75%)  3/47 (6.38%) 
Vascular disorders         
Flushing  1  0/59 (0.00%)  0/49 (0.00%)  24/57 (42.11%)  25/47 (53.19%) 
Hot Flush  1  0/59 (0.00%)  0/49 (0.00%)  5/57 (8.77%)  1/47 (2.13%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
Results Point of Contact
Name/Title: Biogen Study Medical Director
Organization: Biogen
Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT01156311     History of Changes
Other Study ID Numbers: 109MS201
First Submitted: July 1, 2010
First Posted: July 2, 2010
Results First Submitted: May 26, 2015
Results First Posted: June 9, 2015
Last Update Posted: March 21, 2017