Phase 3 Efficacy and Safety Study of BG00012 in Pediatric... | NCT02283853

NCT02283853

ID	Type	Description	Link
2013-002318-11	EudraCT Number

Status Module

Label	Type	Description	Intervention Names
BG00012	Experimental	Participants will receive the recommended dose of 240 mg orally, twice a day	Drug: dimethyl fumarate
IFN β-1a (Avonex)	Active Comparator	Participants will receive the recommended dose of 30 μg (weekly)	Drug: Interferon β-1a

Name	Type	Description	Arm Group Labels	Other Names
dimethyl fumarate	Drug	administered orally	BG00012	BG00012

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Part 1: Proportion of Participants Free of New or Newly Enlarging T2 Hyperintense Lesions on Brain Magnetic Resonance Imaging (MRI) Scans	Participants who were free of new or newly enlarging T2 hyperintense lesions were assessed on Brain MRI scans.	At Week 96
Part 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	An adverse event (AE) was any unfavorable and unintended sign (including an abnormal assessment such as an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. 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, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in a birth defect. TEAEs were defined as AEs occurring or worsening after beginning study treatment (after the first dose).	From Week 96 up to last follow-up visit (up to Week 340)
Part 2: Number of Participants Who Discontinued Study Treatment Due to an AE	An AE was any unfavorable and unintended sign (including an abnormal assessment such as an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.	From Week 96 up to last follow-up visit (up to Week 340)

Secondary Outcomes

Measure	Description	Time Frame
Part 1: Number of New or Newly Enlarged T2 Hyperintense Lesions on Brain MRI Scans	The number of new or newly enlarging T2 hyperintense lesions that developed in each participant was assessed on Brain MRI scans.	At Weeks 24 and Week 96
Part 1: Proportion of Participants Free of New or Newly Enlarging T2 Hyperintense Lesions on Brain MRI Scans

Eligibility Module

Eligibility Criteria

Key Inclusion Criteria:

Males and females aged from 10 to less than 18 years old at the time of informed consent or assent.
Must have a body weight of ≥30 kg.
Must have a diagnosis of RRMS (consensus definition for pediatric RRMS [Krupp 2013]).
Must be ambulatory with a baseline EDSS score between 0 and 5.5, inclusive.
Must have experienced at least 1 of the following 3 conditions: a) at least 1 relapse within the last 12 months prior to Day 1 with a prior brain MRI demonstrating lesions consistent with MS; b) at least 2 relapses within the last 24 months prior to Day 1, with a prior brain MRI demonstrating lesions consistent with MS; c) evidence of Gd-enhancing lesions of the brain on an MRI performed within the 6 weeks prior to Day 1.
Must be neurologically stable, with no evidence of relapse within 50 days prior to Day 1 and no evidence of corticosteroid treatment within 30 days prior to Day 1.
Participants of childbearing potential who are sexually active must be willing to practice effective contraception during the study and be willing and able to continue contraception for at least 30 days after their final dose of study treatment.

Key Exclusion Criteria:

Primary progressive, secondary progressive, or progressive relapsing MS (as defined by [Lublin and Reingold 1996]). These conditions require the presence of continuous clinical disease worsening over a period of at least 3 months. Participants with these conditions may also have superimposed relapses but are distinguished from relapsing-remitting participants by the lack of clinically stable periods or clinical improvement.
Disorders mimicking MS, such as other demyelinating disorders (e.g., acute disseminated encephalomyelitis), systemic autoimmune disorders (e.g., Sjögren disease, lupus erythematosus), metabolic disorders (e.g., dystrophies), and infectious disorders.
History of premalignant or malignant disease. Participants with basal cell carcinoma that has been completely excised prior to screening will remain eligible.
History of severe allergic or anaphylactic reactions, or known drug hypersensitivity to DMF, fumaric acid esters, or interferon beta-1a (IFN Beta-1a).
History of abnormal laboratory results indicative of any significant endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, renal, and/or any other major disease that would preclude participation in a clinical study.
History of clinically significant cardiovascular, pulmonary, GI, dermatologic, growth, developmental, psychiatric (including depression), neurologic (other than MS), and/or other major disease that would preclude participation in a clinical study.
History of human immunodeficiency virus.
An MS relapse that has occurred within 50 days prior to Day 1 AND/OR the participant has not stabilized from a previous relapse prior to Day 1.
Other unspecified reasons that, in the opinion of the Investigator or Biogen Idec, make the participant unsuitable for enrollment.

NOTE: Other protocol-defined inclusion/exclusion criteria may apply

Name	Affiliation	Role
Medical Director	Biogen	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Boston Children's Hospital		Boston	Massachusetts	2115	United States
The Rector and Visitors of the University of Virginia

PubMed Identifier	Type	Citation	Retractions
36169959	Derived	Vermersch P, Scaramozza M, Levin S, Alroughani R, Deiva K, Pozzilli C, Lyons J, Mokliatchouk O, Pultz J, N'Dure F, Liu S, Badwan R, Branco F, Hood-Humphrey V, Franchimont N, Hanna J, Maghzi AH. Effect of Dimethyl Fumarate vs Interferon beta-1a in Patients With Pediatric-Onset Multiple Sclerosis: The CONNECT Randomized Clinical Trial. JAMA Netw Open. 2022 Sep 1;5(9):e2230439. doi: 10.1001/jamanetworkopen.2022.30439.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Part 1: BG00012	Participants received a starting dose of BG00012 120 milligrams (mg) twice a day (BID), orally for 7 days, followed by a maintenance dose of 240 mg BID orally, up to Week 96.
FG001	Part 1: Interferon β-1a

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jul 25, 2017	Apr 2, 2026

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Part 1: Proportion of Participants Free of New or Newly Enlarging T2 Hyperintense Lesions on Brain Magnetic Resonance Imaging (MRI) Scans

Participants who were free of new or newly enlarging T2 hyperintense lesions were assessed on Brain MRI scans.

Completers population included participants from the ITT population who completed Week 96 of the study and had MRI data for Week 96. Here, 'overall number of participants analyzed' signifies the number of participants with data available for outcome measure analysis.

Posted

Number

95% Confidence Interval

proportion of participants

At Week 96

ID	Title	Description
OG000	Part 1: BG00012	Participants received a starting dose of BG00012 120 mg BID, orally for 7 days, followed by a maintenance dose of 240 mg BID orally, up to Week 96.
OG001	Part 1: Interferon β-1a	Participants received Interferon β-1a by IM injection at a starting dose of 7.5 μg, followed by dose titration (increase) by 7.5 μg each week for 3 weeks to the recommended dose of 30 μg, which was continued up to Week 96.

Units	Counts
Participants	OG00062 OG00141

Title

Denominators

Categories

Title	Measurements
	OG0000.161(0.080 to 0.277) OG0010.049(0.006 to 0.165)

Primary

Part 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

An adverse event (AE) was any unfavorable and unintended sign (including an abnormal assessment such as an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. 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, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in a birth defect. TEAEs were defined as AEs occurring or worsening after beginning study treatment (after the first dose).

Safety population included all participants who completed Part 1 of the study and received at least one dose of BG00012 in Part 2 (LTE).

Posted

Count of Participants

Participants

From Week 96 up to last follow-up visit (up to Week 340)

ID	Title	Description
OG000	Part 2: BG00012/ BG00012	Participants who received BG00012 in Part 1 received BG00012, 240 mg orally, BID from Week 96 through Week 336.
OG001	Part 2: IFN β-1a/ BG00012	Participants who received Interferon β-1a in Part 1 received BG00012, 120 mg BID for 7 days, followed by a maintenance dose of BG00012 240 mg from Week 96 through Week 336.

Primary

Part 2: Number of Participants Who Discontinued Study Treatment Due to an AE

Safety population included all participants who completed Part 1 of the study and received at least one dose of BG00012 in Part 2 (LTE).

Posted

Count of Participants

Participants

From Week 96 up to last follow-up visit (up to Week 340)

ID	Title	Description
OG000	Part 2: BG00012/ BG00012	Participants who received BG00012 in Part 1 received BG00012, 240 mg orally, BID from Week 96 through Week 336.
OG001	Part 2: IFN β-1a/ BG00012	Participants who received Interferon β-1a in Part 1 received BG00012, 120 mg BID for 7 days, followed by a maintenance dose of BG00012 240 mg from Week 96 through Week 336.

Units	Counts
Participants

Secondary

Part 1: Number of New or Newly Enlarged T2 Hyperintense Lesions on Brain MRI Scans

The number of new or newly enlarging T2 hyperintense lesions that developed in each participant was assessed on Brain MRI scans.

ITT population included all participants who were randomized and received at least one dose of study treatment. Here, 'overall number of participants analyzed' signifies the number of participants with data available for outcome measure analysis. 'Number analyzed' signifies the number of participants available for analysis at a specified time point.

Posted

Mean

Standard Deviation

number of lesions

At Weeks 24 and Week 96

ID	Title	Description
OG000	Part 1: BG00012	Participants received a starting dose of BG00012 120 mg BID, orally for 7 days, followed by a maintenance dose of 240 mg BID orally, up to Week 96.
OG001	Part 1: Interferon β-1a	Participants received Interferon β-1a by IM injection at a starting dose of 7.5 μg, followed by dose titration (increase) by 7.5 μg each week for 3 weeks to the recommended dose of 30 μg, which was continued up to Week 96.

Units	Counts
Participants

Secondary

Part 1: Proportion of Participants Free of New or Newly Enlarging T2 Hyperintense Lesions on Brain MRI Scans

Participants who were free of new or newly enlarging T2 hyperintense lesions were assessed on Brain MRI scans.

Posted

Number

95% Confidence Interval

proportion of participants

At Weeks 24 and 48

ID	Title	Description
OG000	Part 1: BG00012	Participants received a starting dose of BG00012 120 mg BID, orally for 7 days, followed by a maintenance dose of 240 mg BID orally, up to Week 96.
OG001	Part 1: Interferon β-1a	Participants received Interferon β-1a by IM injection at a starting dose of 7.5 μg, followed by dose titration (increase) by 7.5 μg each week for 3 weeks to the recommended dose of 30 μg, which was continued up to Week 96.

Units	Counts

Secondary

Part 1: Proportion of Participants Free of New MRI Activity as Measured by Brain MRI Scans

Participants free of Gd-enhancing MRI lesions and new or newly enlarging T2 MRI lesions were assessed on Brain MRI Scans.

Posted

Number

95% Confidence Interval

proportion of participants

At Weeks 24, 48, and 96

ID	Title	Description
OG000	Part 1: BG00012	Participants received a starting dose of BG00012 120 mg BID, orally for 7 days, followed by a maintenance dose of 240 mg BID orally, up to Week 96.
OG001	Part 1: Interferon β-1a	Participants received Interferon β-1a by IM injection at a starting dose of 7.5 μg, followed by dose titration (increase) by 7.5 μg each week for 3 weeks to the recommended dose of 30 μg, which was continued up to Week 96.

Units	Counts

Secondary

Part 1: Time to First Relapse

Relapses are defined as new or recurrent neurologic symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the examining neurologist. The time to first relapse was defined as the time from the first dose in Part 1 up to the first relapse. Time to First Relapse was estimated by Kaplan-Meier method.

Posted

Median

Inter-Quartile Range

weeks

Up to Week 96

ID	Title	Description
OG000	Part 1: BG00012	Participants received a starting dose of BG00012 120 mg BID, orally for 7 days, followed by a maintenance dose of 240 mg BID orally, up to Week 96.
OG001	Part 1: Interferon β-1a	Participants received Interferon β-1a by IM injection at a starting dose of 7.5 μg, followed by dose titration (increase) by 7.5 μg each week for 3 weeks to the recommended dose of 30 μg, which was continued up to Week 96.

Units	Counts

Secondary

Part 1: Proportion of Relapse-Free Participants

Relapses are defined as new or recurrent neurologic symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the examining neurologist. The proportion of relapse-free participants was estimated using the Kaplan-Meier method.

ITT population included all participants who were randomized and received at least 1 dose of study treatment.

Posted

Number

proportion of participants

Up to Week 96

ID	Title	Description
OG000	Part 1: BG00012	Participants received a starting dose of BG00012 120 mg BID, orally for 7 days, followed by a maintenance dose of 240 mg BID orally, up to Week 96.
OG001	Part 1: Interferon β-1a	Participants received Interferon β-1a by IM injection at a starting dose of 7.5 μg, followed by dose titration (increase) by 7.5 μg each week for 3 weeks to the recommended dose of 30 μg, which was continued up to Week 96.

Units	Counts
Participants

Secondary

Part 1: Annualized Relapse Rate (ARR)

ARR is calculated as the total number of relapses that occurred during the study divided by the total number of participant-years. ARR was analyzed using negative binomial regression model.

ITT population included all participants who were randomized and received at least 1 dose of study treatment.

Posted

Number

95% Confidence Interval

relapses per participant-year

At Weeks 48 and 96

ID	Title	Description
OG000	Part 1: BG00012	Participants received a starting dose of BG00012 120 mg BID, orally for 7 days, followed by a maintenance dose of 240 mg BID orally, up to Week 96.
OG001	Part 1: Interferon β-1a	Participants received Interferon β-1a by IM injection at a starting dose of 7.5 μg, followed by dose titration (increase) by 7.5 μg each week for 3 weeks to the recommended dose of 30 μg, which was continued up to Week 96.

Units	Counts
Participants	OG000

Secondary

Part 1: Number of Participants With TEAEs and TESAEs

An AE was any unfavorable and unintended sign (including an abnormal assessment such as an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. 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, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in a birth defect. TEAEs were defined as AEs occurring or worsening after beginning study treatment (after the first dose).

In Part 1, adverse events were assessed in the ITT population. ITT population included all participants who were randomized and received at least 1 dose of study treatment.

Posted

Count of Participants

Participants

From Day 1 up to Week 96

ID	Title	Description
OG000	Part 1: BG00012	Participants received a starting dose of BG00012 120 mg BID, orally for 7 days, followed by a maintenance dose of 240 mg BID orally, up to Week 96.
OG001	Part 1: Interferon β-1a	Participants received Interferon β-1a by IM injection at a starting dose of 7.5 μg, followed by dose titration (increase) by 7.5 μg each week for 3 weeks to the recommended dose of 30 μg, which was continued up to Week 96.

Secondary

Part 1: Change From Baseline in Vital Signs (Temperature)

Negative change from baseline indicated reduction in temperature.

In Part 1, adverse events were assessed in the ITT population. ITT population included all participants who were randomized and received at least one dose of study treatment. Here, 'overall number of participants analyzed' signifies the number of participants with data available for outcome measure analysis. 'Number analyzed' signifies the number of participants available for analysis at a specified time point.

Posted

Mean

Standard Deviation

degree Celsius

Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84 and 96

ID	Title	Description
OG000	Part 1: BG00012	Participants received a starting dose of BG00012 120 mg BID, orally for 7 days, followed by a maintenance dose of 240 mg BID orally, up to Week 96.
OG001	Part 1: Interferon β-1a	Participants received Interferon β-1a by IM injection at a starting dose of 7.5 μg, followed by dose titration (increase) by 7.5 μg each week for 3 weeks to the recommended dose of 30 μg, which was continued up to Week 96.

Units	Counts
Participants

Secondary

Part 1: Change From Baseline in Vital Signs (Pulse Rate)

Negative change from baseline indicated reduction in pulse rate.

Posted

Mean

Standard Deviation

beats per minute

Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84 and 96

ID	Title	Description
OG000	Part 1: BG00012	Participants received a starting dose of BG00012 120 mg BID, orally for 7 days, followed by a maintenance dose of 240 mg BID orally, up to Week 96.
OG001	Part 1: Interferon β-1a	Participants received Interferon β-1a by IM injection at a starting dose of 7.5 μg, followed by dose titration (increase) by 7.5 μg each week for 3 weeks to the recommended dose of 30 μg, which was continued up to Week 96.

Units	Counts
Participants

Secondary

Part 1: Change From Baseline in Vital Signs (Blood Pressure)

Negative change from baseline indicated reduction in blood pressure.

Posted

Mean

Standard Deviation

millimeters of mercury (mmHg)

Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84 and 96

ID	Title	Description
OG000	Part 1: BG00012	Participants received a starting dose of BG00012 120 mg BID, orally for 7 days, followed by a maintenance dose of 240 mg BID orally, up to Week 96.
OG001	Part 1: Interferon β-1a	Participants received Interferon β-1a by IM injection at a starting dose of 7.5 μg, followed by dose titration (increase) by 7.5 μg each week for 3 weeks to the recommended dose of 30 μg, which was continued up to Week 96.

Units	Counts
Participants

Secondary

Part 1: Change From Baseline in Vital Signs (Respiratory Rate)

Negative change from baseline indicated reduction in respiratory rate.

Posted

Mean

Standard Deviation

breaths per minute

Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84 and 96

ID	Title	Description
OG000	Part 1: BG00012	Participants received a starting dose of BG00012 120 mg BID, orally for 7 days, followed by a maintenance dose of 240 mg BID orally, up to Week 96.
OG001	Part 1: Interferon β-1a	Participants received Interferon β-1a by IM injection at a starting dose of 7.5 μg, followed by dose titration (increase) by 7.5 μg each week for 3 weeks to the recommended dose of 30 μg, which was continued up to Week 96.

Units	Counts

Secondary

Part 1: Number of Participants With Shifts From Baseline in Electrocardiograms (ECG) Abnormalities

Clinical significance of abnormalities in ECG was determined based on the investigator's discretion. Shift to abnormal indicated values that were normal or unknown at baseline and shifted to abnormal values post-baseline.

In Part 1, adverse events were assessed in the ITT population. ITT population included all participants who were randomized and received at least one dose of study treatment. The overall number of participants analyzed signifies the number of participants whose baseline value was not abnormal and who had at least one post-baseline value.

Posted

Count of Participants

Participants

Up to Week 96

ID	Title	Description
OG000	Part 1: BG00012	Participants received a starting dose of BG00012 120 mg BID, orally for 7 days, followed by a maintenance dose of 240 mg BID orally, up to Week 96.
OG001	Part 1: Interferon β-1a	Participants received Interferon β-1a by IM injection at a starting dose of 7.5 μg, followed by dose titration (increase) by 7.5 μg each week for 3 weeks to the recommended dose of 30 μg, which was continued up to Week 96.

Units	Counts

Secondary

Part 1: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters)

Hematology parameters included leukocytes, erythrocytes, hemoglobin, hematocrit, platelets, eosinophils, lymphocytes, monocytes and neutrophils. These parameters were flagged as low, normal, or high relative to parameter's normal range or as unknown if no result was available. Here, shift to low indicated values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicated values that were normal, low or unknown at baseline and shifted to high postbaseline values. The categories with at least one participant with shift from baseline in these parameters are reported.

In Part 1, adverse events were assessed in the ITT population. ITT population included all participants who were randomized and received at least one dose of study treatment. Here, 'number analyzed' signifies the number of participants with data available for analysis of the specified hematology parameter.

Posted

Count of Participants

Participants

Baseline up to Week 96

ID	Title	Description
OG000	Part 1: BG00012	Participants received a starting dose of BG00012 120 mg BID, orally for 7 days, followed by a maintenance dose of 240 mg BID orally, up to Week 96.
OG001	Part 1: Interferon β-1a	Participants received Interferon β-1a by IM injection at a starting dose of 7.5 μg, followed by dose titration (increase) by 7.5 μg each week for 3 weeks to the recommended dose of 30 μg, which was continued up to Week 96.

Secondary

Part 1: Change From Baseline in Coagulation Parameters [Activated Partial Thromboplastin Time (aPTT)]

A negative change from baseline indicated a reduction in aPTT.

In Part 1, adverse events were assessed in the ITT population. ITT population included all participants who were randomized and received at least one dose of study treatment. Here, 'overall number of participants analyzed' signifies the number of participants with data available for outcome measure analysis. 'Number analyzed' signifies number of participants evaluable for this outcome measure.

Posted

Mean

Standard Deviation

seconds

Baseline, Weeks 24, 48 and 96

ID	Title	Description
OG000	Part 1: BG00012	Participants received a starting dose of BG00012 120 mg BID, orally for 7 days, followed by a maintenance dose of 240 mg BID orally, up to Week 96.
OG001	Part 1: Interferon β-1a	Participants received Interferon β-1a by IM injection at a starting dose of 7.5 μg, followed by dose titration (increase) by 7.5 μg each week for 3 weeks to the recommended dose of 30 μg, which was continued up to Week 96.

Units	Counts
Participants

Secondary

Part 1: Change From Baseline in Coagulation Parameters [Prothrombin Time (PT)]

A negative change from baseline indicated a reduction in PT.

In Part 1, adverse events were assessed in the ITT population. ITT population included all participants who were randomized and received at least one dose of study treatment. Here, 'overall number of participants analyzed' signifies the number of participants with data available for outcome measure analysis. 'Number analyzed' signifies number of participants evaluable for this outcome measure.

Posted

Mean

Standard Deviation

seconds

Baseline, Weeks 24, 48 and 96

ID	Title	Description
OG000	Part 1: BG00012	Participants received a starting dose of BG00012 120 mg BID, orally for 7 days, followed by a maintenance dose of 240 mg BID orally, up to Week 96.
OG001	Part 1: Interferon β-1a	Participants received Interferon β-1a by IM injection at a starting dose of 7.5 μg, followed by dose titration (increase) by 7.5 μg each week for 3 weeks to the recommended dose of 30 μg, which was continued up to Week 96.

Units	Counts
Participants

Secondary

Part 1: Change From Baseline in Coagulation Parameters [International Normalized Ratio (INR)]

A negative change from baseline indicated a reduction in clotting time.

In Part 1, adverse events were assessed in the ITT population. ITT population included all participants who were randomized and received at least one dose of study treatment. Here, 'overall number of participants analyzed' signifies the number of participants with data available for outcome measure analysis. 'Number analyzed' signifies number of participants evaluable for this outcome measure.

Posted

Mean

Standard Deviation

ratio

Baseline, Weeks 24, 48 and 96

ID	Title	Description
OG000	Part 1: BG00012	Participants received a starting dose of BG00012 120 mg BID, orally for 7 days, followed by a maintenance dose of 240 mg BID orally, up to Week 96.
OG001	Part 1: Interferon β-1a	Participants received Interferon β-1a by IM injection at a starting dose of 7.5 μg, followed by dose titration (increase) by 7.5 μg each week for 3 weeks to the recommended dose of 30 μg, which was continued up to Week 96.

Units	Counts
Participants

Secondary

Part 1: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters)

Parameters included sodium, potassium, chloride, bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, urea nitrogen, creatinine, bicarbonate, calcium, magnesium, phosphate, urate and glucose. These parameters were flagged as low, normal or high relative to parameter's normal range or as unknown if no result was available, by Investigator. Here, shift to low indicated values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicated values that were normal, low or unknown at baseline and shifted to high values postbaseline. Categories with at least one participant with shift from baseline in these parameters are reported.

In Part 1, adverse events were assessed in the ITT population. ITT population included all participants who were randomized and received at least one dose of study treatment. Here, 'number analyzed' signifies the number of participants available for analysis of the specified blood chemistry parameter.

Posted

Count of Participants

Participants

Baseline up to Week 96

ID	Title	Description
OG000	Part 1: BG00012	Participants received a starting dose of BG00012 120 mg BID, orally for 7 days, followed by a maintenance dose of 240 mg BID orally, up to Week 96.
OG001	Part 1: Interferon β-1a

Secondary

Part 1: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Urinalysis Parameters)

Urinalysis included assessments of glucose, ketones, occult blood, protein, specific gravity. These parameters were flagged as low, normal, or high relative to parameter's normal range or as unknown if no result was available, by the Investigator. Here, shift to low indicated values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicated values that were normal, low or unknown at baseline and shifted to high postbaseline. The categories with at least one participant with shift from baseline in these parameters are reported.

In Part 1, adverse events were assessed in the ITT population. ITT population included all participants who were randomized and received at least 1 dose of study treatment. Here, 'number analyzed' signifies the number of participants with data available for analysis of the specified urinalysis parameter.

Posted

Count of Participants

Participants

Baseline up to Week 96

ID	Title	Description
OG000	Part 1: BG00012	Participants received a starting dose of BG00012 120 mg BID, orally for 7 days, followed by a maintenance dose of 240 mg BID orally, up to Week 96.
OG001	Part 1: Interferon β-1a	Participants received Interferon β-1a by IM injection at a starting dose of 7.5 μg, followed by dose titration (increase) by 7.5 μg each week for 3 weeks to the recommended dose of 30 μg, which was continued up to Week 96.

Secondary

Part 1: Fatigue Score Measured by the Pediatric Quality of Life Inventory (PedsQL) Multidimensional Fatigue Scale

The PedsQL multidimensional fatigue questionnaire was answered by the participant (self-assessment) and parent. The fatigue scale contains 18 questions in 3 fatigue dimensions: general fatigue, sleep/rest fatigue and cognitive fatigue. Each item was scored on 5-point Likert scale (0=never to 4=almost always). Each individual score was then reversed (subtracted from 4) and linearly transformed as follows: 0=100, 1=75, 2=50, 3=25, 4=0. For each dimension, total score was calculated as the sum of all the items/number of items answered. A higher total score indicated fewer problems.

ITT population included all participants who were randomized and received at least 1 dose of study treatment. Here, 'overall number of participants analyzed' signifies the number of participants with data available for outcome measure analysis. 'Number analyzed' signifies the number of participants available for analysis at a specified time point.

Posted

Mean

Standard Deviation

score on a scale

Up to Week 96

ID	Title	Description
OG000	Part 1: BG00012	Participants received a starting dose of BG00012 120 mg BID, orally for 7 days, followed by a maintenance dose of 240 mg BID orally, up to Week 96.
OG001	Part 1: Interferon β-1a	Participants received Interferon β-1a by IM injection at a starting dose of 7.5 μg, followed by dose titration (increase) by 7.5 μg each week for 3 weeks to the recommended dose of 30 μg, which was continued up to Week 96.

Secondary

Part 1: Quality of Life (QOL) as Measured by the PedsQL

The PedsQL QOL questionnaire was answered by the participant (self-assessment) and parent. The QoL scale contains 23 questions in 4 dimensions: Physical Functioning, Emotional Fatigue, Social Fatigue and School Fatigue. Each item was scored on 5-point Likert scale (0=never to 4=almost always). Each individual score was then reversed (subtracted from 4) and linearly transformed as follows: 0=100, 1=75, 2=50, 3=25, 4=0. For each dimension, total score was calculated as the sum of all the items/number of items answered. A higher total score indicated better quality of life.

Posted

Mean

Standard Deviation

score on a scale

Up to Week 96

ID	Title	Description
OG000	Part 1: BG00012	Participants received a starting dose of BG00012 120 mg BID, orally for 7 days, followed by a maintenance dose of 240 mg BID orally, up to Week 96.
OG001	Part 1: Interferon β-1a	Participants received Interferon β-1a by IM injection at a starting dose of 7.5 μg, followed by dose titration (increase) by 7.5 μg each week for 3 weeks to the recommended dose of 30 μg, which was continued up to Week 96.

Secondary

Part 1: Change From Baseline in the Expanded Disability Status Scale (EDSS) Score

The EDSS measures the disability status of participants with multiple sclerosis on a scale that ranges from 0 to 10. The first levels 1.0 to 4.5 refer to people with a high degree of ambulatory ability and the subsequent levels 5.0 to 9.5 refer to the loss of ambulatory ability. The range of main categories include (0) = normal neurologic exam; to (5) = ambulatory without aid or rest for 200 meters; disability severe enough to impair full daily activities; to (10) = death due to MS with higher scores indicating more disability. A negative change from baseline indicated an improvement in the disability.

ITT population included all participants who were randomized and received at least 1 dose of study treatment. 'Number analyzed' signifies the number of participants available for analysis at a specified time point.

Posted

Mean

Standard Deviation

score on a scale

Baseline, Week 96

ID	Title	Description
OG000	Part 1: BG00012	Participants received a starting dose of BG00012 120 mg BID, orally for 7 days, followed by a maintenance dose of 240 mg BID orally, up to Week 96.
OG001	Part 1: Interferon β-1a	Participants received Interferon β-1a by IM injection at a starting dose of 7.5 μg, followed by dose titration (increase) by 7.5 μg each week for 3 weeks to the recommended dose of 30 μg, which was continued up to Week 96.

Secondary

Part 2: Annualized Relapse Rate (ARR)

ARR is calculated as the total number of relapses that occurred during the study divided by the total number of participant-years. ARR was analyzed using negative binomial regression model.

ITT population included all participants who completed Part 1 of the study and received at least 1 dose of BG00012 in Part 2 (LTE).

Posted

Number

95% Confidence Interval

relapses per participant-year

From Baseline (Week 96) up to Week 336

ID	Title	Description
OG000	Part 2: BG00012/ BG00012	Participants who received BG00012 in Part 1 received BG00012, 240 mg orally, BID from Week 96 through Week 336.
OG001	Part 2: IFN β-1a/ BG00012	Participants who received Interferon β-1a in Part 1 received BG00012, 120 mg BID for 7 days, followed by a maintenance dose of BG00012 240 mg from Week 96 through Week 336.

Units	Counts
Participants	OG000

Secondary

Part 2: Change From Baseline in the Expanded Disability Status Scale (EDSS) Score

The EDSS measures the disability status of participants with multiple sclerosis on a scale that ranges from 0 to 10. The first levels 1.0 to 4.5 refer to people with a high degree of ambulatory ability and the subsequent levels 5.0 to 9.5 refer to the loss of ambulatory ability. The range of main categories include (0) = normal neurologic exam; to (5) = ambulatory without aid or rest for 200 meters; disability severe enough to impair full daily activities; to (10) = death due to MS. A negative change from baseline indicated an improvement in the disability.

ITT population included all participants who completed Part 1 of the study and received at least 1 dose of BG00012 in Part 2 (LTE). Here, 'overall number of participants analyzed' signifies the number of participants with data available for outcome measure analysis. 'Number analyzed' signifies the number of participants available for analysis at a specified time point.

Posted

Mean

Standard Deviation

score on a scale

Baseline (Week 96), Week 336

ID	Title	Description
OG000	Part 2: BG00012/ BG00012	Participants who received BG00012 in Part 1 received BG00012, 240 mg orally, BID from Week 96 through Week 336.
OG001	Part 2: IFN β-1a/ BG00012	Participants who received Interferon β-1a in Part 1 received BG00012, 120 mg BID for 7 days, followed by a maintenance dose of BG00012 240 mg from Week 96 through Week 336.

Secondary

Part 2: Change From Baseline in Brief Visuospatial Memory Test - Revised (BVMT-R) Score

BVMT-R is used to assess learning/memory. In this test, six abstract designs are presented for 10 sec. The display is removed from view, and participants render the stimuli via pencil on paper, manual responses. Each design receives from 0 to 2 points, representing accuracy and location. There are three Learning Trials, and the score is reported as the total number of points earned over the trials. Thus, scores range from 0 to 12 per trial; total score range is 0 to 36 for all three trials. Scores were converted to standardized scores using normative data, ranging from 2-86. The lower the score, the more severe the cognitive impairment while higher scores reflect better visuospatial memory.

Posted

Mean

Standard Deviation

score on a scale

Baseline (Week 96), Weeks 144,192, 240, 288 and 336

ID	Title	Description
OG000	Part 2: BG00012/ BG00012	Participants who received BG00012 in Part 1 received BG00012, 240 mg orally, BID from Week 96 through Week 336.
OG001	Part 2: IFN β-1a/ BG00012

Secondary

Part 2: Change From Baseline in Symbol Digit Modalities Test (SDMT) Score

SDMT is used to assess processing speed. It consists of 9 abstract symbols. Each symbol is paired with a single digit. The participant is provided with a key, showing each symbol digit pair. In addition, the participants are shown several rows of the 9 symbols, which are arranged pseudo-randomly, without the digit. Participants are asked to voice the digit associated with each symbol as rapidly as possible for 90 seconds. The SDMT score ranges from 0 to 110, where higher scores indicate improvement in cognitive functioning and lower scores indicate worsening.

Posted

Mean

Standard Deviation

score on a scale

Baseline (Week 96), Weeks 144,192, 240, 288 and 336

ID	Title	Description
OG000	Part 2: BG00012/ BG00012	Participants who received BG00012 in Part 1 received BG00012, 240 mg orally, BID from Week 96 through Week 336.
OG001	Part 2: IFN β-1a/ BG00012	Participants who received Interferon β-1a in Part 1 received BG00012, 120 mg BID for 7 days, followed by a maintenance dose of BG00012 240 mg from Week 96 through Week 336.

Secondary

Part 2: Number of Participants With or Without School Progression

Participants or caregivers were posed the following question: "During the past year, did [you/the participant] progress from one [class/grade-level] to the next in school?" Responses were recorded as Yes (participant advanced to the next grade) or No (participant did not advance).

Posted

Count of Participants

Participants

At Weeks 144, 192, 240, 288 and 336

ID	Title	Description
OG000	Part 2: BG00012/ BG00012	Participants who received BG00012 in Part 1 received BG00012, 240 mg orally, BID from Week 96 through Week 336.
OG001	Part 2: IFN β-1a/ BG00012	Participants who received Interferon β-1a in Part 1 received BG00012, 120 mg BID for 7 days, followed by a maintenance dose of BG00012 240 mg from Week 96 through Week 336.

Units

Secondary

Part 2: Change From Baseline in Vital Signs (Temperature)

Negative change from baseline indicated reduction in temperature.

Safety population included all participants who completed Part 1 of the study and received at least 1 dose of BG00012 in Part 2 (LTE). Here, 'overall number of participants analyzed' signifies the number of participants with data available for outcome measure analysis. 'Number analyzed' signifies the number of participants available for analysis at a specified time point.

Posted

Mean

Standard Deviation

degree Celsius

Baseline (Week 96), Weeks 120,144, 168, 192, 216, 240, 264, 288, 312, 336, and 340

ID	Title	Description
OG000	Part 2: BG00012/ BG00012	Participants who received BG00012 in Part 1 received BG00012, 240 mg orally, BID from Week 96 through Week 336.
OG001	Part 2: IFN β-1a/ BG00012	Participants who received Interferon β-1a in Part 1 received BG00012, 120 mg BID for 7 days, followed by a maintenance dose of BG00012 240 mg from Week 96 through Week 336.

Units	Counts
Participants

Secondary

Part 2: Change From Baseline in Vital Signs (Pulse Rate)

Negative change from baseline indicated reduction in pulse rate.

Posted

Mean

Standard Deviation

beats per minute

Baseline (Week 96), Weeks 120,144, 168, 192, 216, 240, 264, 288, 312, 336, and 340

ID	Title	Description
OG000	Part 2: BG00012/ BG00012	Participants who received BG00012 in Part 1 received BG00012, 240 mg orally, BID from Week 96 through Week 336.
OG001	Part 2: IFN β-1a/ BG00012	Participants who received Interferon β-1a in Part 1 received BG00012, 120 mg BID for 7 days, followed by a maintenance dose of BG00012 240 mg from Week 96 through Week 336.

Units	Counts
Participants

Secondary

Part 2: Change From Baseline in Vital Signs (Blood Pressure)

Negative change from baseline indicated reduction in blood pressure.

Posted

Mean

Standard Deviation

mmHg

Baseline (Week 96), Weeks 120,144, 168, 192, 216, 240, 264, 288, 312, 336, and 340

ID	Title	Description
OG000	Part 2: BG00012/ BG00012	Participants who received BG00012 in Part 1 received BG00012, 240 mg orally, BID from Week 96 through Week 336.
OG001	Part 2: IFN β-1a/ BG00012	Participants who received Interferon β-1a in Part 1 received BG00012, 120 mg BID for 7 days, followed by a maintenance dose of BG00012 240 mg from Week 96 through Week 336.

Units	Counts
Participants

Secondary

Part 2: Change From Baseline in Vital Signs (Respiratory Rate)

Negative change from baseline indicated reduction in respiratory rate.

Posted

Mean

Standard Deviation

breaths per minute

Baseline (Week 96), Weeks 120,144, 168, 192, 216, 240, 264, 288, 312, 336, and 340

ID	Title	Description
OG000	Part 2: BG00012/ BG00012	Participants who received BG00012 in Part 1 received BG00012, 240 mg orally, BID from Week 96 through Week 336.
OG001	Part 2: IFN β-1a/ BG00012	Participants who received Interferon β-1a in Part 1 received BG00012, 120 mg BID for 7 days, followed by a maintenance dose of BG00012 240 mg from Week 96 through Week 336.

Units	Counts
Participants

Secondary

Part 2: Number of Participants With Shifts From Baseline in ECG Abnormalities

Posted

Count of Participants

Participants

From Baseline (Week 96) to Week 336

ID	Title	Description
OG000	Part 2: BG00012/ BG00012	Participants who received BG00012 in Part 1 received BG00012, 240 mg orally, BID from Week 96 through Week 336.
OG001	Part 2: IFN β-1a/ BG00012	Participants who received Interferon β-1a in Part 1 received BG00012, 120 mg BID for 7 days, followed by a maintenance dose of BG00012 240 mg from Week 96 through Week 336.

Units	Counts
Participants

Secondary

Part 2: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters)

Posted

Count of Participants

Participants

Baseline (Week 96) up to Week 340

ID	Title	Description
OG000	Part 2: BG00012/ BG00012	Participants who received BG00012 in Part 1 received BG00012, 240 mg orally, BID from Week 96 through Week 336.
OG001	Part 2: IFN β-1a/ BG00012	Participants who received Interferon β-1a in Part 1 received BG00012, 120 mg BID for 7 days, followed by a maintenance dose of BG00012 240 mg from Week 96 through Week 336.

Secondary

Part 2: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters)

Parameters included potassium, bilirubin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, urea nitrogen, creatinine, bicarbonate, calcium, magnesium, phosphate, urate and glucose. These parameters were flagged as low, normal or high relative to parameter's normal range or as unknown if no result was available, by Investigator. Here, shift to low indicated values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicated values that were normal, low or unknown at baseline and shifted to high values postbaseline. Categories with at least one participant with shift from baseline in these parameters are reported.

Posted

Count of Participants

Participants

Baseline (Week 96) up to Week 340

ID	Title	Description
OG000	Part 2: BG00012/ BG00012	Participants who received BG00012 in Part 1 received BG00012, 240 mg orally, BID from Week 96 through Week 336.
OG001	Part 2: IFN β-1a/ BG00012

Secondary

Part 2: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Urinalysis Parameters)

Urinalysis included assessments of erythrocytes, leukocytes and specific gravity. These parameters were flagged as low, normal, or high relative to parameter's normal range or as unknown if no result was available, by the Investigator. Here, shift to low indicated values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicated values that were normal, low or unknown at baseline and shifted to high postbaseline. The categories with at least one participant with shift from baseline in these parameters are reported.

Posted

Count of Participants

Participants

Baseline up to Week 340

ID	Title	Description
OG000	Part 2: BG00012/ BG00012	Participants who received BG00012 in Part 1 received BG00012, 240 mg orally, BID from Week 96 through Week 336.
OG001	Part 2: IFN β-1a/ BG00012	Participants who received Interferon β-1a in Part 1 received BG00012, 120 mg BID for 7 days, followed by a maintenance dose of BG00012 240 mg from Week 96 through Week 336.

Secondary

Part 2: Change From Baseline in Height

Posted

Mean

Standard Deviation

centimeters (cm)

Baseline (Week 96), Weeks 120,144, 168, 192, 216, 240, 264, 288, 312, 336, and 340

ID	Title	Description
OG000	Part 2: BG00012/ BG00012	Participants who received BG00012 in Part 1 received BG00012, 240 mg orally, BID from Week 96 through Week 336.
OG001	Part 2: IFN β-1a/ BG00012	Participants who received Interferon β-1a in Part 1 received BG00012, 120 mg BID for 7 days, followed by a maintenance dose of BG00012 240 mg from Week 96 through Week 336.

Units	Counts
Participants	OG000

Secondary

Part 2: Change From Baseline in Weight

Posted

Mean

Standard Deviation

kilograms (Kg)

Baseline (Week 96), Weeks 120,144, 168, 192, 216, 240, 264, 288, 312, 336, and 340

ID	Title	Description
OG000	Part 2: BG00012/ BG00012	Participants who received BG00012 in Part 1 received BG00012, 240 mg orally, BID from Week 96 through Week 336.
OG001	Part 2: IFN β-1a/ BG00012	Participants who received Interferon β-1a in Part 1 received BG00012, 120 mg BID for 7 days, followed by a maintenance dose of BG00012 240 mg from Week 96 through Week 336.

Units	Counts
Participants	OG000

Secondary

Part 2: Change From Baseline in Bone Age

Bone age was tested until the participant reached a bone age of 16 years.

Posted

Mean

Standard Deviation

Years

Baseline (Week 96), Weeks 144, 192 and 240

ID	Title	Description
OG000	Part 2: BG00012/ BG00012	Participants who received BG00012 in Part 1 received BG00012, 240 mg orally, BID from Week 96 through Week 336.
OG001	Part 2: IFN β-1a/ BG00012	Participants who received Interferon β-1a in Part 1 received BG00012, 120 mg BID for 7 days, followed by a maintenance dose of BG00012 240 mg from Week 96 through Week 336.

Units	Counts
Participants

Secondary

Part 2: Number of Male Participants by Tanner Stage Assessment

Tanner pubertal staging in males was assessed for testes and scrotum development and pubic hair growth, progressing from stage 1 (prepubertal) to stage 5 (adult). Assessments ended when bone age reached ≥16 years. Testes and scrotum stages were: 1-prepubertal; 2-enlargement of testes, scrotum reddens, texture change; 3-Enlargement of penis, further growth of testes; 4-Increased size of penis with growth in breadth and development of glans; testes and scrotum larger, scrotum skin darker; 5-adult genitalia. Pubic hair stages were: 1-prepubertal; 2-Sparse growth of long, slightly pigmented hair, straight or curled; 3-Darker, coarser and more curled hair, spreading sparsely over junction of pubes; 4-Hair adult in type, but covering smaller area than in adult; no spread to medial surface of thighs; 5-Adult in type and quantity, with horizontal distribution.

Safety population included all participants who completed Part 1 of the study and received at least 1 dose of BG00012 in Part 2 (LTE). Here, 'overall number of participants analyzed' signifies the number of male participants. 'Number analyzed' signifies the number of participants available for analysis at a specified time point.

Posted

Count of Participants

Participants

At Weeks 96, 144, 192, 240, 288 and 336

ID	Title	Description
OG000	Part 2: BG00012/ BG00012	Participants who received BG00012 in Part 1 received BG00012, 240 mg orally, BID from Week 96 through Week 336.
OG001	Part 2: IFN β-1a/ BG00012

Secondary

Part 2: Number of Female Participants by Tanner Stage Assessment

Tanner pubertal staging in females was assessed for breast development and pubic hair growth, progressing from stage 1 (prepubertal) to stage 5 (adult). Assessments ended when bone age reached ≥16 years or the participant was post-menarche. Breast development stages: 1-prepubertal; 2-breast bud stage with elevation of breast and papilla; enlargement of areola, 3-further enlargement of breast and areola; no separation of their contour; 4-areola and papilla form secondary mound above level of breast; 5-mature stage: projection of papilla only, related to recession of areola. Pubic hair stages: 1-prepubertal (can see velus hair similar to abdominal wall); 2-sparse growth of long, slightly pigmented hair, straight or curled, mainly on labia; 3-Darker, coarser and more curled hair, spreading sparsely over junction of pubes; 4-hair adult in type, but covering smaller area than in adult; no spread to medial surface of thighs; 5-adult in type and quantity, with horizontal distribution.

Safety population included all participants who completed Part 1 of the study and received at least 1 dose of BG00012 in Part 2 (LTE). Here, 'overall number of participants analyzed' signifies the number of female participants. 'Number analyzed' signifies the number of participants available for analysis at a specified time point.

Posted

Count of Participants

Participants

At Weeks 96, 144, 192, 240, 288 and 336

ID	Title	Description
OG000	Part 2: BG00012/ BG00012	Participants who received BG00012 in Part 1 received BG00012, 240 mg orally, BID from Week 96 through Week 336.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Part 1: BG00012	Participants received a starting dose of BG00012 120 mg BID, orally for 7 days, followed by a maintenance dose of 240 mg BID orally, up to Week 96.	78	18	78	74	78
EG001	Part 1: Interferon β-1a	Participants received Interferon β-1a by IM injection at a starting dose of 7.5 μg, followed by dose titration (increase) by 7.5 μg each week for 3 weeks to the recommended dose of 30 μg, which was continued up to Week 96.	72	21	72	69	72
EG002	Part 2: BG00012/ BG00012	Participants who received BG00012 in Part 1 received BG00012, 240 mg orally, BID from Week 96 through Week 336.	57	8	57	48	57
EG003	Part 2: IFN β-1a/ BG00012	Participants who received Interferon β-1a in Part 1 received BG00012, 120 mg BID for 7 days, followed by a maintenance dose of BG00012 240 mg from Week 96 through Week 336.	35	2	35	31	35

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0000 affected78 at risk EG0011 affected72 at risk EG0020 affected57 at risk EG0030 affected35 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0001 affected78 at risk EG0010 affected72 at risk EG0020 affected57 at risk EG003
Congenital cystic kidney disease	Congenital, familial and genetic disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0000 affected78 at risk EG0010 affected72 at risk EG0021 affected57 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0001 affected78 at risk EG0010 affected72 at risk EG0020 affected57 at risk EG003
Influenza like illness	General disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0000 affected78 at risk EG0011 affected72 at risk EG0020 affected57 at risk EG003
Hepatocellular injury	Hepatobiliary disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0000 affected78 at risk EG0011 affected72 at risk EG0020 affected57 at risk EG003
Herpes zoster	Infections and infestations	MedDRA 23.1, 28.0	Systematic Assessment	EG0000 affected78 at risk EG0010 affected72 at risk EG0021 affected57 at risk EG003
Pneumonia pneumococcal	Infections and infestations	MedDRA 23.1, 28.0	Systematic Assessment	EG0001 affected78 at risk EG0010 affected72 at risk EG0020 affected57 at risk EG003
Tonsillitis	Infections and infestations	MedDRA 23.1, 28.0	Systematic Assessment	EG0001 affected78 at risk EG0010 affected72 at risk EG0020 affected57 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 23.1, 28.0	Systematic Assessment	EG0001 affected78 at risk EG0010 affected72 at risk EG0020 affected57 at risk EG003
Forearm fracture	Injury, poisoning and procedural complications	MedDRA 23.1, 28.0	Systematic Assessment	EG0001 affected78 at risk EG0010 affected72 at risk EG0020 affected57 at risk EG003
Joint dislocation	Injury, poisoning and procedural complications	MedDRA 23.1, 28.0	Systematic Assessment	EG0000 affected78 at risk EG0010 affected72 at risk EG0021 affected57 at risk EG003
Wound	Injury, poisoning and procedural complications	MedDRA 23.1, 28.0	Systematic Assessment	EG0000 affected78 at risk EG0010 affected72 at risk EG0021 affected57 at risk EG003
Groin pain	Musculoskeletal and connective tissue disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0000 affected78 at risk EG0011 affected72 at risk EG0020 affected57 at risk EG003
Epilepsy	Nervous system disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0001 affected78 at risk EG0010 affected72 at risk EG0021 affected57 at risk EG003
Generalised tonic-clonic seizure	Nervous system disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0001 affected78 at risk EG0010 affected72 at risk EG0020 affected57 at risk EG003
Multiple sclerosis relapse	Nervous system disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG00013 affected78 at risk EG00118 affected72 at risk EG0023 affected57 at risk EG003
Optic neuritis	Nervous system disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0001 affected78 at risk EG0010 affected72 at risk EG0021 affected57 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0000 affected78 at risk EG0011 affected72 at risk EG0020 affected57 at risk EG003
Presyncope	Nervous system disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0001 affected78 at risk EG0010 affected72 at risk EG0020 affected57 at risk EG003
Relapsing multiple sclerosis	Nervous system disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0000 affected78 at risk EG0011 affected72 at risk EG0020 affected57 at risk EG003
Syncope	Nervous system disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0000 affected78 at risk EG0010 affected72 at risk EG0021 affected57 at risk EG003
Abortion missed	Pregnancy, puerperium and perinatal conditions	MedDRA 23.1, 28.0	Systematic Assessment	EG0000 affected78 at risk EG0010 affected72 at risk EG0021 affected57 at risk EG003
Borderline personality disorder	Psychiatric disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0000 affected78 at risk EG0010 affected72 at risk EG0021 affected57 at risk EG003
Suicide attempt	Psychiatric disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0001 affected78 at risk EG0010 affected72 at risk EG0020 affected57 at risk EG003
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0001 affected78 at risk EG0010 affected72 at risk EG0020 affected57 at risk EG003
Social problem	Social circumstances	MedDRA 23.1, 28.0	Systematic Assessment	EG0001 affected78 at risk EG0010 affected72 at risk EG0020 affected57 at risk EG003
Hypertension	Vascular disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0000 affected78 at risk EG0011 affected72 at risk EG0020 affected57 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Leukopenia	Blood and lymphatic system disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0000 affected78 at risk EG0010 affected72 at risk EG0020 affected57 at risk EG0032 affected35 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0001 affected78 at risk EG0010 affected72 at risk EG0021 affected57 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0004 affected78 at risk EG0011 affected72 at risk EG0020 affected57 at risk EG003
Hypothyroidism	Endocrine disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0001 affected78 at risk EG0010 affected72 at risk EG0020 affected57 at risk EG003
Diplopia	Eye disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0005 affected78 at risk EG0010 affected72 at risk EG0021 affected57 at risk EG003
Eye pain	Eye disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0002 affected78 at risk EG0015 affected72 at risk EG0024 affected57 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG00032 affected78 at risk EG0015 affected72 at risk EG0027 affected57 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG00013 affected78 at risk EG0011 affected72 at risk EG0022 affected57 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0005 affected78 at risk EG0012 affected72 at risk EG0021 affected57 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG00015 affected78 at risk EG0014 affected72 at risk EG0024 affected57 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0008 affected78 at risk EG0011 affected72 at risk EG0021 affected57 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG00013 affected78 at risk EG0016 affected72 at risk EG0023 affected57 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0001 affected78 at risk EG0013 affected72 at risk EG0025 affected57 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG00018 affected78 at risk EG0016 affected72 at risk EG0025 affected57 at risk EG003
Asthenia	General disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0004 affected78 at risk EG0016 affected72 at risk EG0022 affected57 at risk EG003
Chills	General disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0000 affected78 at risk EG0014 affected72 at risk EG0020 affected57 at risk EG003
Fatigue	General disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0002 affected78 at risk EG0017 affected72 at risk EG0022 affected57 at risk EG003
Influenza like illness	General disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0002 affected78 at risk EG00136 affected72 at risk EG0020 affected57 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0004 affected78 at risk EG0010 affected72 at risk EG0020 affected57 at risk EG003
Pyrexia	General disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0008 affected78 at risk EG00117 affected72 at risk EG00210 affected57 at risk EG003
Covid-19	Infections and infestations	MedDRA 23.1, 28.0	Systematic Assessment	EG0000 affected78 at risk EG0010 affected72 at risk EG00211 affected57 at risk EG003
Cystitis	Infections and infestations	MedDRA 23.1, 28.0	Systematic Assessment	EG0004 affected78 at risk EG0010 affected72 at risk EG0022 affected57 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 23.1, 28.0	Systematic Assessment	EG0009 affected78 at risk EG0015 affected72 at risk EG0023 affected57 at risk EG003
Influenza	Infections and infestations	MedDRA 23.1, 28.0	Systematic Assessment	EG0008 affected78 at risk EG0013 affected72 at risk EG0024 affected57 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 23.1, 28.0	Systematic Assessment	EG00018 affected78 at risk EG0019 affected72 at risk EG0028 affected57 at risk EG003
Otitis media	Infections and infestations	MedDRA 23.1, 28.0	Systematic Assessment	EG0000 affected78 at risk EG0011 affected72 at risk EG0023 affected57 at risk EG003
Pharyngitis	Infections and infestations	MedDRA 23.1, 28.0	Systematic Assessment	EG0005 affected78 at risk EG0014 affected72 at risk EG0022 affected57 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA 23.1, 28.0	Systematic Assessment	EG0000 affected78 at risk EG0011 affected72 at risk EG0020 affected57 at risk EG003
Rhinitis	Infections and infestations	MedDRA 23.1, 28.0	Systematic Assessment	EG0008 affected78 at risk EG0016 affected72 at risk EG0026 affected57 at risk EG003
Tonsillitis	Infections and infestations	MedDRA 23.1, 28.0	Systematic Assessment	EG0004 affected78 at risk EG0016 affected72 at risk EG0025 affected57 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 23.1, 28.0	Systematic Assessment	EG0009 affected78 at risk EG0013 affected72 at risk EG0024 affected57 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 23.1, 28.0	Systematic Assessment	EG0003 affected78 at risk EG0012 affected72 at risk EG0025 affected57 at risk EG003
Viral infection	Infections and infestations	MedDRA 23.1, 28.0	Systematic Assessment	EG0003 affected78 at risk EG0012 affected72 at risk EG0020 affected57 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 23.1, 28.0	Systematic Assessment	EG0002 affected78 at risk EG0010 affected72 at risk EG0024 affected57 at risk EG003
Immunisation reaction	Injury, poisoning and procedural complications	MedDRA 23.1, 28.0	Systematic Assessment	EG0000 affected78 at risk EG0010 affected72 at risk EG0023 affected57 at risk EG003
Ligament sprain	Injury, poisoning and procedural complications	MedDRA 23.1, 28.0	Systematic Assessment	EG0004 affected78 at risk EG0011 affected72 at risk EG0022 affected57 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0006 affected78 at risk EG0017 affected72 at risk EG0024 affected57 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0006 affected78 at risk EG0016 affected72 at risk EG0028 affected57 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0002 affected78 at risk EG0019 affected72 at risk EG0020 affected57 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0001 affected78 at risk EG0014 affected72 at risk EG0020 affected57 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0004 affected78 at risk EG0018 affected72 at risk EG0022 affected57 at risk EG003
Dizziness	Nervous system disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0004 affected78 at risk EG0011 affected72 at risk EG0024 affected57 at risk EG003
Headache	Nervous system disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG00022 affected78 at risk EG00126 affected72 at risk EG00213 affected57 at risk EG003
Multiple sclerosis relapse	Nervous system disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG00023 affected78 at risk EG00123 affected72 at risk EG00215 affected57 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0006 affected78 at risk EG0014 affected72 at risk EG0023 affected57 at risk EG003
Tremor	Nervous system disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0000 affected78 at risk EG0014 affected72 at risk EG0022 affected57 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0000 affected78 at risk EG0010 affected72 at risk EG0022 affected57 at risk EG003
Proteinuria	Renal and urinary disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0002 affected78 at risk EG0014 affected72 at risk EG0024 affected57 at risk EG003
Dysmenorrhoea	Reproductive system and breast disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG00013 affected78 at risk EG0015 affected72 at risk EG0026 affected57 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG00011 affected78 at risk EG0012 affected72 at risk EG0024 affected57 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG00014 affected78 at risk EG0014 affected72 at risk EG0028 affected57 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0008 affected78 at risk EG0010 affected72 at risk EG0023 affected57 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0006 affected78 at risk EG0010 affected72 at risk EG0020 affected57 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG00011 affected78 at risk EG0011 affected72 at risk EG0022 affected57 at risk EG003
Flushing	Vascular disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG00030 affected78 at risk EG0011 affected72 at risk EG0024 affected57 at risk EG003
Hot flush	Vascular disorders	MedDRA 23.1, 28.0	Systematic Assessment	EG0007 affected78 at risk EG0011 affected72 at risk EG0021 affected57 at risk EG003

ID	Term
D009103	Multiple Sclerosis
D020278	Demyelinating Autoimmune Diseases, CNS
D020274	Autoimmune Diseases of the Nervous System
D009422	Nervous System Diseases
D003711	Demyelinating Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases

ID	Term
D005650	Fumarates
D003998	Dicarboxylic Acids
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D009930	Organic Chemicals
D016899	Interferon-beta
D007370	Interferon Type I
D007372	Interferons
D016207	Cytokines
D036341	Intercellular Signaling Peptides and Proteins
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D011506	Proteins
D001685	Biological Factors

ID	Title	Description
BG000	Part 1: BG00012	Participants received a starting dose of BG00012 120 mg BID, orally for 7 days, followed by a maintenance dose of 240 mg BID orally, up to Week 96.
BG001	Part 1: Interferon β-1a	Participants received Interferon β-1a by IM injection at a starting dose of 7.5 μg, followed by dose titration (increase) by 7.5 μg each week for 3 weeks to the recommended dose of 30 μg, which was continued up to Week 96.
BG002	Total	Total of all reporting groups