Trial Outcomes & Findings for BG00012 Phase 2 Combination Study in Participants With Multiple Sclerosis (NCT NCT01156311)

Last Updated: 2017-03-21

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

108 participants

Primary outcome timeframe

AEs were collected from enrollment until the final study visit (Week 26 +/-5 days).

Results posted on

2017-03-21

Participant Flow

Participant milestones

Participant milestones
Measure	Monotherapy Period: Interferon Beta (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. The monotherapy period included the 8 weeks prior to the first dose of dimethyl fumarate.	Monotherapy Period: Glatiramer Acetate (GA) 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.	Add-on Therapy Period: Dimethyl Fumarate Add-on to IFNß 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.	Add-on Therapy Period: Dimethyl Fumarate Add-on to GA 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.
2-Month Monotherapy Period STARTED	59	49	0	0
2-Month Monotherapy Period COMPLETED	57	47	0	0
2-Month Monotherapy Period NOT COMPLETED	2	2	0	0
6-month Add-on Therapy Period STARTED	0	0	57	47
6-month Add-on Therapy Period Completed BG00012 Combination Therapy	0	0	45	38
6-month Add-on Therapy Period COMPLETED	0	0	45	37
6-month Add-on Therapy Period NOT COMPLETED	0	0	12	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Monotherapy Period: Interferon Beta (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. The monotherapy period included the 8 weeks prior to the first dose of dimethyl fumarate.	Monotherapy Period: Glatiramer Acetate (GA) 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.	Add-on Therapy Period: Dimethyl Fumarate Add-on to IFNß 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.	Add-on Therapy Period: Dimethyl Fumarate Add-on to GA 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.
2-Month Monotherapy Period Withdrawal by Subject	1	1	0	0
2-Month Monotherapy Period Physician Decision	0	1	0	0
2-Month Monotherapy Period Other	1	0	0	0
6-month Add-on Therapy Period Adverse Event	0	0	7	6
6-month Add-on Therapy Period Lost to Follow-up	0	0	2	0
6-month Add-on Therapy Period Disease Activity	0	0	1	2
6-month Add-on Therapy Period Physician Decision	0	0	1	0
6-month Add-on Therapy Period Other	0	0	1	2

Baseline Characteristics

BG00012 Phase 2 Combination Study in Participants With Multiple Sclerosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Interferon Beta (IFNß) and BG00012 (Dimethyl Fumarate) n=57 Participants 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).	Glatiramer Acetate (GA) and BG00012 (Dimethyl Fumarate) n=47 Participants 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 n=104 Participants Total of all reporting groups
Age, Continuous	39.5 years STANDARD_DEVIATION 7.58 • n=5 Participants	40.7 years STANDARD_DEVIATION 8.44 • n=7 Participants	40.1 years STANDARD_DEVIATION 7.96 • n=5 Participants
Age, Customized 18 to 19 years	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Age, Customized 20 to 29 years	5 participants n=5 Participants	3 participants n=7 Participants	8 participants n=5 Participants
Age, Customized 30 to 39 years	18 participants n=5 Participants	22 participants n=7 Participants	40 participants n=5 Participants
Age, Customized 40 to 49 years	27 participants n=5 Participants	15 participants n=7 Participants	42 participants n=5 Participants
Age, Customized 50 to 55 years	6 participants n=5 Participants	7 participants n=7 Participants	13 participants n=5 Participants
Sex: Female, Male Female	40 Participants n=5 Participants	29 Participants n=7 Participants	69 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	18 Participants n=7 Participants	35 Participants n=5 Participants

PRIMARY outcome

Timeframe: AEs were collected from enrollment until the final study visit (Week 26 +/-5 days).

Population: 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.

Outcome measures

Outcome measures
Measure	Monotherapy Period: IFNß n=57 Participants 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.	Monotherapy Period: GA n=47 Participants 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.
Summary of Treatment-emergent Adverse Events (TEAEs) Occurring Post-BG00012 Dosing (Add-on Therapy Period) Participants with a TEAE	95 percentage of participants	100 percentage of participants
Summary of Treatment-emergent Adverse Events (TEAEs) Occurring Post-BG00012 Dosing (Add-on Therapy Period) Participants with a moderate or severe TEAE	72 percentage of participants	70 percentage of participants
Summary of Treatment-emergent Adverse Events (TEAEs) Occurring Post-BG00012 Dosing (Add-on Therapy Period) Participants with a severe TEAE	14 percentage of participants	15 percentage of participants
Summary of Treatment-emergent Adverse Events (TEAEs) Occurring Post-BG00012 Dosing (Add-on Therapy Period) Participants with a related TEAE	74 percentage of participants	87 percentage of participants
Summary of Treatment-emergent Adverse Events (TEAEs) Occurring Post-BG00012 Dosing (Add-on Therapy Period) Participants with a serious TEAE	4 percentage of participants	2 percentage of participants
Summary of Treatment-emergent Adverse Events (TEAEs) Occurring Post-BG00012 Dosing (Add-on Therapy Period) Participants discontinuing BG00012 due to a TEAE	14 percentage of participants	17 percentage of participants
Summary of Treatment-emergent Adverse Events (TEAEs) Occurring Post-BG00012 Dosing (Add-on Therapy Period) Participants withdrawing from study due to a TEAE	14 percentage of participants	17 percentage of participants

PRIMARY outcome

Timeframe: collected from the start of BG00012 administration through to Week 26 +/- 5 days

Population: 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.

Percentage of participants with potentially clinically significant hematology laboratory abnormalities.

Outcome measures

Outcome measures
Measure	Monotherapy Period: IFNß n=56 Participants 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.	Monotherapy Period: GA n=47 Participants 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.
Potentially Clinically Significant Hematology Laboratory Abnormalities for Combination Therapy White Blood Cells (total) < 3.0*10^9/L	9 percentage of participants	2 percentage of participants
Potentially Clinically Significant Hematology Laboratory Abnormalities for Combination Therapy White Blood Cells (total) ≥ 16*10^9/L	2 percentage of participants	2 percentage of participants
Potentially Clinically Significant Hematology Laboratory Abnormalities for Combination Therapy Lymphocytes < 0.8*10^9/L	32 percentage of participants	6 percentage of participants
Potentially Clinically Significant Hematology Laboratory Abnormalities for Combination Therapy Lymphocytes < 0.5*10^9/L	7 percentage of participants	4 percentage of participants
Potentially Clinically Significant Hematology Laboratory Abnormalities for Combination Therapy Lymphocytes > 12*10^9/L	0 percentage of participants	0 percentage of participants
Potentially Clinically Significant Hematology Laboratory Abnormalities for Combination Therapy Neutrophils ≤ 1.0*10^9/L	0 percentage of participants	0 percentage of participants
Potentially Clinically Significant Hematology Laboratory Abnormalities for Combination Therapy Neutrophils < 1.5*10^9/L	13 percentage of participants	2 percentage of participants
Potentially Clinically Significant Hematology Laboratory Abnormalities for Combination Therapy Neutrophils ≥ 12*10^9/L	2 percentage of participants	4 percentage of participants
Potentially Clinically Significant Hematology Laboratory Abnormalities for Combination Therapy Red Blood Cells ≤ 3.3*10^12/L	0 percentage of participants	0 percentage of participants
Potentially Clinically Significant Hematology Laboratory Abnormalities for Combination Therapy Red Blood Cells ≥ 6.8*10^12/L	0 percentage of participants	0 percentage of participants
Potentially Clinically Significant Hematology Laboratory Abnormalities for Combination Therapy Hemoglobin g/L ≤ 100	0 percentage of participants	0 percentage of participants
Potentially Clinically Significant Hematology Laboratory Abnormalities for Combination Therapy Platelet Count ≤ 100*10^9/L	0 percentage of participants	0 percentage of participants
Potentially Clinically Significant Hematology Laboratory Abnormalities for Combination Therapy Platelet Count ≥ 600*10^9/L	0 percentage of participants	0 percentage of participants

PRIMARY outcome

Timeframe: collected from the start of BG00012 administration through to Week 26 +/- 5 days

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.

Outcome measures

Outcome measures
Measure	Monotherapy Period: IFNß n=57 Participants 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.	Monotherapy Period: GA n=47 Participants 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.
Maximum Post-Baseline Values: Liver Enzymes for Combination Therapy ALT ≥ 3*ULN	5 percentage of participants	2 percentage of participants
Maximum Post-Baseline Values: Liver Enzymes for Combination Therapy ALT > 5*ULN	2 percentage of participants	0 percentage of participants
Maximum Post-Baseline Values: Liver Enzymes for Combination Therapy ALT > 10*ULN	0 percentage of participants	0 percentage of participants
Maximum Post-Baseline Values: Liver Enzymes for Combination Therapy ALT > 20*ULN	0 percentage of participants	0 percentage of participants
Maximum Post-Baseline Values: Liver Enzymes for Combination Therapy AST ≤ 1*ULN	68 percentage of participants	64 percentage of participants
Maximum Post-Baseline Values: Liver Enzymes for Combination Therapy AST > 1*ULN	32 percentage of participants	36 percentage of participants
Maximum Post-Baseline Values: Liver Enzymes for Combination Therapy AST ≥ 3*ULN	2 percentage of participants	0 percentage of participants
Maximum Post-Baseline Values: Liver Enzymes for Combination Therapy AST > 5*ULN	0 percentage of participants	0 percentage of participants
Maximum Post-Baseline Values: Liver Enzymes for Combination Therapy AST > 10*ULN	0 percentage of participants	0 percentage of participants
Maximum Post-Baseline Values: Liver Enzymes for Combination Therapy AST > 20*ULN	0 percentage of participants	0 percentage of participants
Maximum Post-Baseline Values: Liver Enzymes for Combination Therapy GGT ≤ 1*ULN	72 percentage of participants	85 percentage of participants
Maximum Post-Baseline Values: Liver Enzymes for Combination Therapy GGT > 1*ULN	28 percentage of participants	15 percentage of participants
Maximum Post-Baseline Values: Liver Enzymes for Combination Therapy GGT ≥ 3*ULN	4 percentage of participants	0 percentage of participants
Maximum Post-Baseline Values: Liver Enzymes for Combination Therapy GGT > 5*ULN	2 percentage of participants	0 percentage of participants
Maximum Post-Baseline Values: Liver Enzymes for Combination Therapy GGT > 10*ULN	0 percentage of participants	0 percentage of participants
Maximum Post-Baseline Values: Liver Enzymes for Combination Therapy GGT > 20*ULN	0 percentage of participants	0 percentage of participants
Maximum Post-Baseline Values: Liver Enzymes for Combination Therapy Total Bilirubin ≤ 1*ULN	98 percentage of participants	94 percentage of participants
Maximum Post-Baseline Values: Liver Enzymes for Combination Therapy ALT ≤ 1*ULN	47 percentage of participants	47 percentage of participants
Maximum Post-Baseline Values: Liver Enzymes for Combination Therapy ALT > 1*ULN	53 percentage of participants	53 percentage of participants
Maximum Post-Baseline Values: Liver Enzymes for Combination Therapy Total Bilirubin > 1*ULN	2 percentage of participants	6 percentage of participants
Maximum Post-Baseline Values: Liver Enzymes for Combination Therapy Total Bilirubin > 1.5*ULN	0 percentage of participants	4 percentage of participants
Maximum Post-Baseline Values: Liver Enzymes for Combination Therapy Total Bilirubin > 2*ULN	0 percentage of participants	2 percentage of participants
Maximum Post-Baseline Values: Liver Enzymes for Combination Therapy ALT/AST ≥ 3ULN + Total Bilirubin > 1.5ULN	0 percentage of participants	0 percentage of participants
Maximum Post-Baseline Values: Liver Enzymes for Combination Therapy ALT/AST ≥ 3ULN + Total Bilirubin > 2ULN	0 percentage of participants	0 percentage of participants

PRIMARY outcome

Timeframe: collected from the start of BG00012 administration through to Week 26 +/- 5 days

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Monotherapy Period: IFNß n=57 Participants 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.	Monotherapy Period: GA n=47 Participants 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.
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy Urine microscopy (male): 0-3 rbc/hpf; n=9, 16	100 percentage of participants	75 percentage of participants
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy Urine microscopy (male): 4-10 rbc/hpf; n=9, 16	0 percentage of participants	6 percentage of participants
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy Urine microscopy (male): 11-20 rbc/hpf; n=9, 16	0 percentage of participants	13 percentage of participants
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy Urine microscopy (male): 21-149 rbc/hpf; n=9, 16	0 percentage of participants	6 percentage of participants
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy Urine microscopy (male): ≥ 150 rbc/hpf; n=9, 16	0 percentage of participants	0 percentage of participants
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy Urine microscopy (female): 0-8 rbc/hpf; n=25, 28	76 percentage of participants	86 percentage of participants
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy Urine microscopy (female): 9-20 rbc/hpf; n=25, 28	8 percentage of participants	4 percentage of participants
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy Urine microscopy (female): 21-30 rbc/hpf; n=25, 28	4 percentage of participants	0 percentage of participants
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy Urine microscopy (female): 31-149 rbc/hpf;n=25, 28	0 percentage of participants	7 percentage of participants
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy Urine microscopy (female): ≥150 rbc/hpf; n=25, 28	12 percentage of participants	4 percentage of participants
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy Urine blood: normal/negative; n=57, 47	75 percentage of participants	64 percentage of participants
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy Urine blood: trace; n=57, 47	7 percentage of participants	9 percentage of participants
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy Urine blood: 1+; n=57, 47	5 percentage of participants	15 percentage of participants
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy Urine blood: 2+; n=57, 47	7 percentage of participants	11 percentage of participants
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy Urine blood: 3+; n=57, 47	5 percentage of participants	2 percentage of participants
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy Urine protein: normal/negative; n=57, 47	39 percentage of participants	38 percentage of participants
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy Urine protein: trace; n=57, 47	35 percentage of participants	45 percentage of participants
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy Urine protein: 1+; n=57, 47	26 percentage of participants	15 percentage of participants
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy Urine protein: 2+; n=57, 47	0 percentage of participants	2 percentage of participants
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy Urine protein: 3+; n=57, 47	0 percentage of participants	0 percentage of participants
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy Urine protein: 4+; n=57, 47	0 percentage of participants	0 percentage of participants
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy Urine glucose: normal/negative; n=57, 47	93 percentage of participants	94 percentage of participants
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy Urine glucose: trace; n=57, 47	2 percentage of participants	0 percentage of participants
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy Urine glucose: 1+; n=57, 47	2 percentage of participants	2 percentage of participants
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy Urine glucose: 2+; n=57, 47	0 percentage of participants	4 percentage of participants
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy Urine glucose: 3+; n=57, 47	2 percentage of participants	0 percentage of participants
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy Urine glucose: 4+; n=57, 47	2 percentage of participants	0 percentage of participants
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy Urine ketone: normal/negative; n=57, 47	47 percentage of participants	57 percentage of participants
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy Urine ketone: trace; n=57, 47	9 percentage of participants	11 percentage of participants
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy Urine ketone: 1+; n=57, 47	26 percentage of participants	28 percentage of participants
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy Urine ketone: 2+; n=57, 47	11 percentage of participants	4 percentage of participants
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy Urine ketone: 3+; n=57, 47	4 percentage of participants	0 percentage of participants
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy Urine ketone: 4+; n=57, 47	4 percentage of participants	0 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: from time of enrollment until day before first administration of BG00012 (Week -8 to Week 0)

Population: The Safety Population for the Monotherapy Period was defined as any participant who took at least 1 dose of background therapy.

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.

Outcome measures

Outcome measures
Measure	Monotherapy Period: IFNß n=59 Participants 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.	Monotherapy Period: GA n=49 Participants 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.
Summary of Adverse Events (AEs) Occurring Before BG00012 Dosing (Monotherapy Period) Participants with an AE	56 percentage of participants	49 percentage of participants
Summary of Adverse Events (AEs) Occurring Before BG00012 Dosing (Monotherapy Period) Participants with a moderate or severe AE	22 percentage of participants	27 percentage of participants
Summary of Adverse Events (AEs) Occurring Before BG00012 Dosing (Monotherapy Period) Participants with a severe AE	3 percentage of participants	0 percentage of participants
Summary of Adverse Events (AEs) Occurring Before BG00012 Dosing (Monotherapy Period) Participants with an SAE	0 percentage of participants	0 percentage of participants
Summary of Adverse Events (AEs) Occurring Before BG00012 Dosing (Monotherapy Period) Participants withdrawing from study due to an AE	0 percentage of participants	0 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Week -8 through Week 24

Population: 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.

The average is calculated as (total number of lesions in non-missing scans / number of non-missing magnetic resonance imaging \[MRI\] scans).

Outcome measures

Outcome measures
Measure	Monotherapy Period: IFNß n=16 Participants 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.	Monotherapy Period: GA n=18 Participants 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.
Average Number of Gadolinium (Gd)-Enhancing Lesions: Week -8, -4, 0 Average Versus Week 16, 20, 24 Average Average number of lesions from Weeks -8, -4, 0	1.06 lesions Standard Deviation 1.011	1.72 lesions Standard Deviation 1.098
Average Number of Gadolinium (Gd)-Enhancing Lesions: Week -8, -4, 0 Average Versus Week 16, 20, 24 Average Average number of lesions from Weeks 16, 20, 24	0.17 lesions Standard Deviation 0.243	0.83 lesions Standard Deviation 2.115
Average Number of Gadolinium (Gd)-Enhancing Lesions: Week -8, -4, 0 Average Versus Week 16, 20, 24 Average Change from average of Weeks -8, -4, 0	-0.90 lesions Standard Deviation 0.902	-0.89 lesions Standard Deviation 2.264

OTHER_PRE_SPECIFIED outcome

Timeframe: Week -4 through Week 24

Population: 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.

The average is calculated as (total number of lesions in non-missing scans / number of non-missing MRI scans).

Outcome measures

Outcome measures
Measure	Monotherapy Period: IFNß n=16 Participants 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.	Monotherapy Period: GA n=17 Participants 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.
Average Number of New Gd-Enhancing Lesions: Weeks -4, 0 Average Versus Weeks 20, 24 Average Average number of lesions from Weeks -4, 0	0.91 lesions Standard Deviation 0.953	0.79 lesions Standard Deviation 0.985
Average Number of New Gd-Enhancing Lesions: Weeks -4, 0 Average Versus Weeks 20, 24 Average Average number of lesions from Weeks 20, 24	0.06 lesions Standard Deviation 0.171	0.18 lesions Standard Deviation 0.303
Average Number of New Gd-Enhancing Lesions: Weeks -4, 0 Average Versus Weeks 20, 24 Average Change from average of Weeks -4, 0	-0.84 lesions Standard Deviation 0.978	-0.62 lesions Standard Deviation 1.054

OTHER_PRE_SPECIFIED outcome

Timeframe: Week -8 to Week 24

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Monotherapy Period: IFNß n=15 Participants 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.	Monotherapy Period: GA n=18 Participants 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.
Number of New or Newly Enlarging T2 Lesions New lesions in the Monotherapy Period	1.23 lesions per month Standard Deviation 1.498	0.89 lesions per month Standard Deviation 1.243
Number of New or Newly Enlarging T2 Lesions New lesions in the Add-on Therapy Period	0.67 lesions per month Standard Deviation 1.257	0.25 lesions per month Standard Deviation 0.293

Adverse Events

Monotherapy Period: IFNß

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Monotherapy Period: GA

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Add-on Therapy Period: IFNß and BG00012

Serious events: 2 serious events

Other events: 53 other events

Deaths: 0 deaths

Add-on Therapy Period: GA and BG00012

Serious events: 1 serious events

Other events: 45 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Monotherapy Period: IFNß n=59 participants at risk A stable dose of one of the IFNß products for up to 8 weeks (until the first dose of BG00012).	Monotherapy Period: GA n=49 participants at risk A stable dose of GA for up to 8 weeks (until the first dose of BG00012).	Add-on Therapy Period: IFNß and BG00012 n=57 participants at risk 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).	Add-on Therapy Period: GA and BG00012 n=47 participants at risk 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).
Infections and infestations Clostridial infection	0.00% 0/59 • 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). 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.	0.00% 0/49 • 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). 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.	0.00% 0/57 • 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). 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.	2.1% 1/47 • 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). 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.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/59 • 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). 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.	0.00% 0/49 • 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). 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.	1.8% 1/57 • 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). 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.	0.00% 0/47 • 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). 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.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/59 • 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). 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.	0.00% 0/49 • 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). 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.	1.8% 1/57 • 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). 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.	0.00% 0/47 • 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). 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.
Gastrointestinal disorders Gastrointestinal pain	0.00% 0/59 • 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). 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.	0.00% 0/49 • 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). 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.	1.8% 1/57 • 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). 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.	0.00% 0/47 • 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). 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.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/59 • 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). 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.	0.00% 0/49 • 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). 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.	1.8% 1/57 • 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). 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.	0.00% 0/47 • 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). 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.

Other adverse events

Additional Information

Biogen Study Medical Director

Biogen

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER