Study of Evobrutinib in Participants With RMS (evolutionR... | NCT04338061

ID	Type	Description	Link
2019-004980-36	EudraCT Number

Name	Class
EMD Serono Research & Development Institute, Inc.	INDUSTRY

Label	Type	Description	Intervention Names
Teriflunomide	Active Comparator		Drug: Teriflunomide
Evobrutinib	Experimental		Drug: Evobrutinib

Name	Type	Description	Arm Group Labels	Other Names
Teriflunomide	Drug	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.

Measure	Description	Time Frame
Double Blind Treatment Period (DBTP) and Double Blind Extension (DBE) Period: Annualized Relapse Rate (ARR)	The qualifying relapse is the occurrence of new or worsening neurological symptoms attributable to Multiple Sclerosis (MS) (for more than [>] 24 hours, no fever, infection, injury, adverse events (AEs), and preceded by a stable or improving neurological state for more than or equal to [>=] 30 days).	Baseline up to 170 weeks

Measure	Description	Time Frame
DBTP and DBE Period: Percentage of Participants Without 12-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS)	Disability progression was defined as increase in EDSS of greater than or equal to [>=] 1 point from baseline EDSS score, if EDSS score at baseline is 5.0 or less and an increase of >=0.5 point, if the baseline score is 5.5. Disability progression is considered sustained for 12 weeks when the initial increase in the EDSS is confirmed at a regularly scheduled visit at least 12 weeks after the initial documentation of neurological worsening. The total EDSS score ranges from 0 (normal) to 10 (death due to multiple sclerosis). Kaplan-Meier method was used to estimate the percentage of participants without 12-week CDP.

Name	Affiliation	Role
Medical Responsible	Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site 752		Cullman	Alabama	35058	United States
Research Site 741

PubMed Identifier	Type	Citation	Retractions
39307151	Result	Montalban X, Vermersch P, Arnold DL, Bar-Or A, Cree BAC, Cross AH, Kubala Havrdova E, Kappos L, Stuve O, Wiendl H, Wolinsky JS, Dahlke F, Le Bolay C, Shen Loo L, Gopalakrishnan S, Hyvert Y, Javor A, Guehring H, Tenenbaum N, Tomic D; evolutionRMS investigators. Safety and efficacy of evobrutinib in relapsing multiple sclerosis (evolutionRMS1 and evolutionRMS2): two multicentre, randomised, double-blind, active-controlled, phase 3 trials. Lancet Neurol. 2024 Nov;23(11):1119-1132. doi: 10.1016/S1474-4422(24)00328-4. Epub 2024 Sep 19.

Label	URL
Trial Awareness and Transparency website	View source

ID	Title	Description
FG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
FG001	Evobrutinib

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Apr 27, 2023	Oct 1, 2024

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

Double Blind Treatment Period (DBTP) and Double Blind Extension (DBE) Period: Annualized Relapse Rate (ARR)

The qualifying relapse is the occurrence of new or worsening neurological symptoms attributable to Multiple Sclerosis (MS) (for more than [>] 24 hours, no fever, infection, injury, adverse events (AEs), and preceded by a stable or improving neurological state for more than or equal to [>=] 30 days).

Full Analysis Set (FAS) included all participants who were randomized to study treatment.

Posted

Mean

95% Confidence Interval

relapses per year

Baseline up to 170 weeks

ID	Title	Description
OG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
OG001	Evobrutinib	Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.

Units	Counts
Participants	OG000583 OG001583

Title

Denominators

Categories

Title	Measurements
	OG0000.11(0.09 to 0.13) OG0010.11(0.09 to 0.13)

Secondary

DBTP and DBE Period: Percentage of Participants Without 12-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS)

Disability progression was defined as increase in EDSS of greater than or equal to [>=] 1 point from baseline EDSS score, if EDSS score at baseline is 5.0 or less and an increase of >=0.5 point, if the baseline score is 5.5. Disability progression is considered sustained for 12 weeks when the initial increase in the EDSS is confirmed at a regularly scheduled visit at least 12 weeks after the initial documentation of neurological worsening. The total EDSS score ranges from 0 (normal) to 10 (death due to multiple sclerosis). Kaplan-Meier method was used to estimate the percentage of participants without 12-week CDP.

Full Analysis Set (FAS) included all participants who were randomized to study treatment. The result reported for this outcome measure are the results from data of combined DBTP and DBE periods.

Posted

Number

95% Confidence Interval

percentage of participants

Week 96 and Week 156 (combined DBTP and DBE periods)

ID	Title	Description
OG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
OG001	Evobrutinib	Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.

Secondary

DBTP and DBE Period: Percentage of Participants Without 24-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS)

Disability progression was defined as increase in EDSS of greater than or equal to [>=] 1 point from baseline EDSS score, if EDSS score at baseline is 5.0 or less and an increase of >=0.5 point, if the baseline score is 5.5. Disability progression is considered sustained for 24 weeks when the initial increase in the EDSS is confirmed at a regularly scheduled visit at least 24 weeks after the initial documentation of neurological worsening. The total EDSS score ranges from 0 (normal) to 10 (death due to multiple sclerosis). Kaplan-Meier method was used to estimate the percentage of participants without 24-week CDP.

Full Analysis Set (FAS) included all participants who were randomized to study treatment. The result reported for this outcome measure are the results from data of combined DBTP and DBE periods.

Posted

Number

95% Confidence Interval

percentage of participants

Week 96 and Week 156 (combined DBTP and DBE periods)

ID	Title	Description
OG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
OG001	Evobrutinib	Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.

Secondary

DBTP and DBE Period: Percentage of Participants With 24-Week Confirmed Disability Improvement (CDI) as Measured by Expanded Disability Status Scale (EDSS)

Disability improvement was defined as a reduction of 1 point from Baseline EDSS score when the Baseline score is >= 2 and less than or equal to [<=] 6 and a reduction of 0.5 point from Baseline EDSS score when the Baseline score is >= 6.5 and <= 9.5. Disability improvement is considered sustained when the initial reduction in the EDSS score is confirmed at a regularly scheduled visit at least 24 weeks after the initial reduction. The total EDSS score ranges from 0 (normal) to 10 (death due to multiple sclerosis). Kaplan-Meier method was used to estimate the percentage of participants with 12-week CDI.

Full Analysis Set (FAS) included all participants who were randomized to study treatment. The result reported for this outcome measure are the results from data of combined DBTP and DBE periods.

Posted

Number

95% Confidence Interval

percentage of participants

Week 96 and Week 156 (combined DBTP and DBE periods)

ID	Title	Description
OG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
OG001	Evobrutinib	Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.

Secondary

DBTP and DBE Period: Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) Score at Week 48, Week 96, Week 120, Week 144 and Week 156

Physical function was assessed with PROMISnq Short Form v2.0 - Physical Function - Multiple Sclerosis 15a (PROMISnq PF(MS) 15a). PROMISnq PF(MS) 15a assesses a participant's abilities and limitations with respect to everyday physical activities. Results are reported as a T-score. In the general population, T-scores have a mean of 50, standard deviation of 10, and range from 10 to 65. Higher T-scores represent higher physical function. Change from baseline in PROMIS PF score was analyzed using Mixed Effect Model for Repeated Measures (MMRM) to evaluate the result of the 2 periods (DBTP and DBE).

Full Analysis Set (FAS) included all participants who were randomized to study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure. The result reported for this outcome measure are the results from data of combined DBTP and DBE periods.

Posted

Least Squares Mean

95% Confidence Interval

units on a scale

Baseline, Week 48, Week 96, Week 120, Week 144 and Week 156 (Combined DBTP and DBE periods)

ID	Title	Description
OG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
OG001

Secondary

DBTP and DBE Period: Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Score at Week 48, Week 96, Week 120, Week 144 and Week 156

PROMIS Fatigue score was assessed with PROMIS Short Form v1.0 - Fatigue - Multiple Sclerosis 8a (PROMIS Fatigue (MS) 8a). PROMIS Fatigue (MS) 8a assesses level of fatigue and its interference on daily activities. Results are reported as a T-score. In the general population, T-scores have a mean of 50, standard deviation of 10, and range from 33 to 85. Higher T-scores represent higher fatigue. Change from baseline in PROMIS fatigue score was analyzed using Mixed Effect Model for Repeated Measures (MMRM) to evaluate the result of the 2 periods (DBTP and DBE).

Posted

Least Squares Mean

95% Confidence Interval

units on a scale

Baseline, Week 48, Week 96, Week 120, Week 144 and Week 156 ((combined DBTP and DBE periods)

ID	Title	Description
OG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
OG001	Evobrutinib

Secondary

DBTP and DBE Period: Total Number of T1 Gadolinium-positive (Gd+) Lesions

Analysis of Gadolinium-positive T1 lesions was done using magnetic resonance imaging (MRI) scans.

Posted

Mean

95% Confidence Interval

lesions per scan

Baseline up to 170 weeks

ID	Title	Description
OG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
OG001	Evobrutinib	Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.

Units	Counts
Participants

Secondary

DBTP and DBE Period: New or Enlarging T2 Lesions Rate

Analysis of new or enlarging T2 lesions rate was done using magnetic resonance imaging (MRI) scans. Negative binomial model for lesion count (summed over scans) includes treatment and covariates based on randomization strata and baseline volume of T2 lesion (continuous), with offset equal to the log of the time in years between the last available MRI scan and the baseline scan.

Posted

Mean

95% Confidence Interval

lesions per year

Baseline up to 170 weeks

ID	Title	Description
OG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
OG001	Evobrutinib	Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.

Secondary

DBTP Period: Neurofilament Light Chain (NfL) Concentration at Week 12

NfL is a biomarker of neuro-axonal damage whose concentration was assessed in blood at Week 12.

Posted

Geometric Mean

95% Confidence Interval

nanogram per liter (ng/L)

Week 12

ID	Title	Description
OG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
OG001	Evobrutinib	Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.

Units	Counts
Participants

Secondary

DBTP and DBE Periods: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Adverse Events of Special Interest (AESIs)

Adverse event (AE): Any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the study drug. Serious AE: an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs: those AEs with an onset date on or after the date of first study intervention administration, or AEs present prior to any study intervention administration but exacerbating after. TEAEs included both Serious TEAEs and non-serious TEAEs. AESIs included liver AEs (possible drug-induced, non-infectious, non-alcoholic, and immune-mediated), infections (serious and opportunistic infections), lipase and amylase elevation, and seizure.

Safety (SAF) analysis set included all participants who received at least one dose of study treatment.

Posted

Count of Participants

Participants

Baseline up to 170 weeks

ID	Title	Description
OG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
OG001	Evobrutinib

Secondary

DBTP and DBE Periods: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity

Severity of adverse events (AE) were assessed by the investigator per the National Cancer Institute- Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0. Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death. Number of participants with Grades 1, 2, 3, 4 and 5 were reported.

Safety (SAF) analysis set included all participants who received at least one dose of study treatment.

Posted

Count of Participants

Participants

Baseline up to 170 weeks

ID	Title	Description
OG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
OG001	Evobrutinib	Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.

Units

Secondary

DBTP and DBE Periods: Change From Baseline in Vital Signs: Diastolic Blood Pressure and Systolic Blood Pressure

Diastolic blood pressure and systolic blood pressure were measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions. Changes in vital signs: diastolic blood pressure and systolic blood pressure from baseline up to 170 weeks were reported.

Safety (SAF) analysis set included all participants who received at least one dose of study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Posted

Mean

Standard Deviation

millimeter of mercury (mmHg)

Baseline up to 170 weeks

ID	Title	Description
OG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
OG001	Evobrutinib	Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.

Secondary

DBTP and DBE Periods: Change From Baseline in Vital Signs: Pulse Rate

Pulse rate was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions. Changes in vital signs: pulse rate from baseline up to 170 weeks was reported.

Posted

Mean

Standard Deviation

beats per minute

Baseline up to 170 weeks

ID	Title	Description
OG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
OG001	Evobrutinib	Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.

Units	Counts

Secondary

DBTP and DBE Periods: Change From Baseline in Vital Signs: Respiratory Rate

Respiratory rate was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions. Changes in vital signs: respiratory rate from baseline up to 170 weeks was reported.

Posted

Mean

Standard Deviation

breaths per minute

Baseline up to 170 weeks

ID	Title	Description
OG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
OG001	Evobrutinib	Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.

Units	Counts

Secondary

DBTP and DBE Periods: Change From Baseline in Vital Signs: Weight

Changes in vital signs: weight from baseline up to 170 weeks was reported.

Posted

Mean

Standard Deviation

kilograms (kg)

Baseline up to 170 weeks

ID	Title	Description
OG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
OG001	Evobrutinib	Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.

Units	Counts
Participants

Secondary

DBTP and DBE Periods: Change From Baseline in Vital Signs: Temperature

Temperature was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions. Changes in vital signs: Temperature from baseline up to 170 weeks was reported.

Posted

Mean

Standard Deviation

degree Celsius

Baseline up to 170 weeks

ID	Title	Description
OG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
OG001	Evobrutinib	Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.

Units	Counts

Secondary

DBTP and DBE Periods: Change From Baseline in Electrocardiograms (ECGs): Heart Rate

Heart rate was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions. Changes in vital signs: heart rate from baseline up to 170 weeks was reported.

Posted

Mean

Standard Deviation

beats per minute

Baseline up to 170 weeks

ID	Title	Description
OG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
OG001	Evobrutinib	Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.

Units	Counts

Secondary

DBTP and DBE Periods: Change From Baseline in Electrocardiograms (ECGs): QT Interval - Fridericia's Correction Formula, PR Interval and QRS Duration

QT Interval - Fridericia's Correction Formula, PR Interval and QRS Duration was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions. Changes in vital signs: QT Interval - Fridericia's Correction Formula, PR Interval and QRS Duration from baseline up to 170 weeks were reported.

Posted

Mean

Standard Deviation

milliseconds (msec)

Baseline up to 170 weeks

ID	Title	Description
OG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
OG001	Evobrutinib	Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.

Secondary

DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Hemoglobin and Erythrocytes Mean Corpuscular Hemoglobin (HGB) Concentration

Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the hematology parameters: erythrocytes mean corpuscular HGB concentration and hemoglobin. Changes in hematology parameters: erythrocytes mean corpuscular HGB concentration and hemoglobin from baseline up to 170 weeks were reported.

Posted

Mean

Standard Deviation

gram per liter (g/L)

Baseline up to 170 weeks

ID	Title	Description
OG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
OG001	Evobrutinib	Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.

Secondary

DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes

Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the hematology parameters: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes. Changes in hematology parameters: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes from baseline up to 170 weeks were reported.

Posted

Mean

Standard Deviation

10^9 cells per liter

Baseline up to 170 weeks

ID	Title	Description
OG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
OG001	Evobrutinib	Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.

Secondary

DBTP and DBE Periods: Change From Baseline in Hematology Parameters: Hematocrit

Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the hematology parameter: Hematocrit. Changes in hematology parameter: Hematocrit from baseline up to 170 weeks was reported.

Posted

Mean

Standard Deviation

percentage of cells

Baseline up to 170 weeks

ID	Title	Description
OG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
OG001	Evobrutinib	Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.

Units	Counts

Secondary

DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the hematology parameter: Erythrocytes Mean Corpuscular Hemoglobin. Changes in hematology parameter: Erythrocytes Mean Corpuscular Hemoglobin from baseline up to 170 weeks was reported.

Posted

Mean

Standard Deviation

picogram

Baseline up to 170 weeks

ID	Title	Description
OG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
OG001	Evobrutinib	Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.

Secondary

DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume

Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the hematology parameter: Erythrocytes Mean Corpuscular Volume. Changes in hematology parameter: Erythrocytes Mean Corpuscular Volume from baseline up to 170 weeks was reported.

Posted

Mean

Standard Deviation

femtoliters

Baseline up to 170 weeks

ID	Title	Description
OG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
OG001	Evobrutinib	Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.

Secondary

DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Bilirubin and Creatinine

Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the biochemistry parameters: Bilirubin and Creatinine. Changes in biochemistry parameters: Bilirubin and Creatinine from baseline up to 170 weeks were reported.

Posted

Mean

Standard Deviation

micromoles per liter (mcmol/L)

Baseline up to 170 weeks

ID	Title	Description
OG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
OG001	Evobrutinib	Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.

Secondary

DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase

Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the biochemistry parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase. Changes in biochemistry parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase from baseline up to 170 weeks were reported.

Posted

Mean

Standard Deviation

units per liter (U/L)

Baseline up to 170 weeks

ID	Title	Description
OG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
OG001	Evobrutinib	Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.

Secondary

DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium

Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the biochemistry parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium. Changes in biochemistry parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium from baseline up to 170 weeks were reported.

Posted

Mean

Standard Deviation

millimole per liter (mmol/L)

Baseline up to 170 weeks

ID	Title	Description
OG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
OG001	Evobrutinib	Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.

Secondary

DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Total Protein and Albumin

Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the biochemistry parameters: Total Protein and Albumin. Changes in biochemistry parameters: Total Protein and Albumin from baseline up to 170 weeks were reported.

Posted

Mean

Standard Deviation

gram per liter (g/L)

Baseline up to 170 weeks

ID	Title	Description
OG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
OG001	Evobrutinib	Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.

Secondary

DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Glomerular Filtration Rate

Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the biochemistry parameter: Glomerular Filtration Rate. Changes in biochemistry parameter: Glomerular Filtration Rate from baseline up to 170 weeks were reported. The Glomerular Filtration Rate was measured as milliliter per minute per 1.73 square meter (mL/min/1.73m^2).

Posted

Mean

Standard Deviation

mL/min/1.73m^2

Baseline up to 170 weeks

ID	Title	Description
OG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
OG001	Evobrutinib	Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.

Secondary

DBTP and DBE Periods: Change From Baseline in Urinalyses Parameter: Potential of Hydrogen (pH) of Urine

Urine samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the urinalyses parameter: pH. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0). Changes in urinalyses parameter: pH from baseline up to 170 weeks was reported.

Posted

Mean

Standard Deviation

Baseline up to 170 weeks

ID	Title	Description
OG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
OG001	Evobrutinib	Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.

Secondary

DBTP and DBE Periods: Change From Baseline in Urinalyses Parameter: Specific Gravity of Urine

Urine samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the urinalyses parameter: Specific Gravity of Urine. Changes in urinalyses parameter: Specific Gravity of Urine from baseline up to 170 weeks was reported.

Posted

Mean

Standard Deviation

Kilogram per cubic meter

Baseline up to 170 weeks

ID	Title	Description
OG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
OG001	Evobrutinib	Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.

Secondary

DBTP and DBE Periods: Absolute Concentrations of Immunoglobulin (Ig) Levels

Absolute Concentrations serum levels of IgG, IgA, IgM were assessed.

Posted

Mean

Standard Deviation

gram per liter (g/L)

At Week 170

ID	Title	Description
OG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
OG001	Evobrutinib	Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.

Units	Counts
Participants

Secondary

DBTP and DBE Periods: Change From Baseline in Immunoglobulin (Ig) Levels

Change from baseline serum levels of IgG, IgA, IgM were assessed.

Posted

Mean

Standard Deviation

gram per liter (g/L)

Baseline up to 170 weeks

ID	Title	Description
OG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
OG001	Evobrutinib	Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute myocardial infarction	Cardiac disorders	MedDRA 26.0	Non-systematic Assessment	EG0001 events1 affected583 at risk EG0010 events0 affected581 at risk
Myocardial infarction	Cardiac disorders	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Chalazion	Eye disorders	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Ileus spastic	Gastrointestinal disorders	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA 26.0	Non-systematic Assessment	EG0001 events1 affected583 at risk EG0010 events0 affected581 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 26.0	Non-systematic Assessment	EG0001 events1 affected583 at risk EG0010 events0 affected581 at risk
Drug-induced liver injury	Hepatobiliary disorders	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Hepatitis	Hepatobiliary disorders	MedDRA 26.0	Non-systematic Assessment	EG0001 events1 affected583 at risk EG0010 events0 affected581 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Acute sinusitis	Infections and infestations	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Appendicitis	Infections and infestations	MedDRA 26.0	Non-systematic Assessment	EG0001 events1 affected583 at risk EG0012 events2 affected581 at risk
COVID-19	Infections and infestations	MedDRA 26.0	Non-systematic Assessment	EG0001 events1 affected583 at risk EG0012 events2 affected581 at risk
COVID-19 pneumonia	Infections and infestations	MedDRA 26.0	Non-systematic Assessment	EG0002 events2 affected583 at risk EG0012 events2 affected581 at risk
Cholecystitis infective	Infections and infestations	MedDRA 26.0	Non-systematic Assessment	EG0001 events1 affected583 at risk EG0010 events0 affected581 at risk
Chronic tonsillitis	Infections and infestations	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Pyelonephritis acute	Infections and infestations	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Renal abscess	Infections and infestations	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Respiratory tract infection viral	Infections and infestations	MedDRA 26.0	Non-systematic Assessment	EG0001 events1 affected583 at risk EG0010 events0 affected581 at risk
Salpingo-oophoritis	Infections and infestations	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Tonsillitis	Infections and infestations	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Urinary tract infection	Infections and infestations	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0013 events2 affected581 at risk
Accidental overdose	Injury, poisoning and procedural complications	MedDRA 26.0	Non-systematic Assessment	EG0002 events2 affected583 at risk EG0010 events0 affected581 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Bladder injury	Injury, poisoning and procedural complications	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Carbon monoxide poisoning	Injury, poisoning and procedural complications	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Concussion	Injury, poisoning and procedural complications	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Craniocerebral injury	Injury, poisoning and procedural complications	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Facial bones fracture	Injury, poisoning and procedural complications	MedDRA 26.0	Non-systematic Assessment	EG0001 events1 affected583 at risk EG0010 events0 affected581 at risk
Foot fracture	Injury, poisoning and procedural complications	MedDRA 26.0	Non-systematic Assessment	EG0001 events1 affected583 at risk EG0010 events0 affected581 at risk
Head injury	Injury, poisoning and procedural complications	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Incisional hernia	Injury, poisoning and procedural complications	MedDRA 26.0	Non-systematic Assessment	EG0001 events1 affected583 at risk EG0010 events0 affected581 at risk
Joint injury	Injury, poisoning and procedural complications	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Muscle injury	Injury, poisoning and procedural complications	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Musculoskeletal injury	Injury, poisoning and procedural complications	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Pelvic fracture	Injury, poisoning and procedural complications	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Scar	Injury, poisoning and procedural complications	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Skin abrasion	Injury, poisoning and procedural complications	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Tibia fracture	Injury, poisoning and procedural complications	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Urinary tract injury	Injury, poisoning and procedural complications	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Vascular pseudoaneurysm	Injury, poisoning and procedural complications	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Alanine aminotransferase increased	Investigations	MedDRA 26.0	Non-systematic Assessment	EG0003 events3 affected583 at risk EG0017 events7 affected581 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 26.0	Non-systematic Assessment	EG0002 events2 affected583 at risk EG0013 events3 affected581 at risk
SARS-CoV-2 test positive	Investigations	MedDRA 26.0	Non-systematic Assessment	EG0001 events1 affected583 at risk EG0010 events0 affected581 at risk
Electrolyte imbalance	Metabolism and nutrition disorders	MedDRA 26.0	Non-systematic Assessment	EG0001 events1 affected583 at risk EG0010 events0 affected581 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Osteonecrosis	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Symphysiolysis	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Non-systematic Assessment	EG0001 events1 affected583 at risk EG0010 events0 affected581 at risk
Haemangioma of liver	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Non-systematic Assessment	EG0001 events1 affected583 at risk EG0010 events0 affected581 at risk
Papillary thyroid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Non-systematic Assessment	EG0002 events2 affected583 at risk EG0010 events0 affected581 at risk
Synovial sarcoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Non-systematic Assessment	EG0002 events2 affected583 at risk EG0014 events4 affected581 at risk
Autonomic neuropathy	Nervous system disorders	MedDRA 26.0	Non-systematic Assessment	EG0001 events1 affected583 at risk EG0010 events0 affected581 at risk
Epilepsy	Nervous system disorders	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Headache	Nervous system disorders	MedDRA 26.0	Non-systematic Assessment	EG0001 events1 affected583 at risk EG0010 events0 affected581 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 26.0	Non-systematic Assessment	EG0001 events1 affected583 at risk EG0010 events0 affected581 at risk
Lumbosacral radiculopathy	Nervous system disorders	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0012 events2 affected581 at risk
Migraine	Nervous system disorders	MedDRA 26.0	Non-systematic Assessment	EG0002 events1 affected583 at risk EG0010 events0 affected581 at risk
Multiple sclerosis relapse	Nervous system disorders	MedDRA 26.0	Non-systematic Assessment	EG0001 events1 affected583 at risk EG0013 events3 affected581 at risk
Syncope	Nervous system disorders	MedDRA 26.0	Non-systematic Assessment	EG0001 events1 affected583 at risk EG0011 events1 affected581 at risk
Abortion spontaneous	Pregnancy, puerperium and perinatal conditions	MedDRA 26.0	Non-systematic Assessment	EG0001 events1 affected583 at risk EG0010 events0 affected581 at risk
Alcoholism	Psychiatric disorders	MedDRA 26.0	Non-systematic Assessment	EG0001 events1 affected583 at risk EG0010 events0 affected581 at risk
Depression	Psychiatric disorders	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Mental disorder	Psychiatric disorders	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Mood disorder due to a general medical condition	Psychiatric disorders	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Neuropsychiatric symptoms	Psychiatric disorders	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Suicidal ideation	Psychiatric disorders	MedDRA 26.0	Non-systematic Assessment	EG0001 events1 affected583 at risk EG0010 events0 affected581 at risk
Suicide attempt	Psychiatric disorders	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Abnormal uterine bleeding	Reproductive system and breast disorders	MedDRA 26.0	Non-systematic Assessment	EG0001 events1 affected583 at risk EG0010 events0 affected581 at risk
Cervical polyp	Reproductive system and breast disorders	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Endometrial hyperplasia	Reproductive system and breast disorders	MedDRA 26.0	Non-systematic Assessment	EG0001 events1 affected583 at risk EG0010 events0 affected581 at risk
Endometriosis	Reproductive system and breast disorders	MedDRA 26.0	Non-systematic Assessment	EG0001 events1 affected583 at risk EG0010 events0 affected581 at risk
Genital haemorrhage	Reproductive system and breast disorders	MedDRA 26.0	Non-systematic Assessment	EG0001 events1 affected583 at risk EG0010 events0 affected581 at risk
Haemorrhagic ovarian cyst	Reproductive system and breast disorders	MedDRA 26.0	Non-systematic Assessment	EG0001 events1 affected583 at risk EG0010 events0 affected581 at risk
Uterine haemorrhage	Reproductive system and breast disorders	MedDRA 26.0	Non-systematic Assessment	EG0002 events1 affected583 at risk EG0010 events0 affected581 at risk
Uterine polyp	Reproductive system and breast disorders	MedDRA 26.0	Non-systematic Assessment	EG0001 events1 affected583 at risk EG0010 events0 affected581 at risk
Emphysema	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Non-systematic Assessment	EG0001 events1 affected583 at risk EG0010 events0 affected581 at risk
Paranasal sinus inflammation	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Non-systematic Assessment	EG0001 events1 affected583 at risk EG0010 events0 affected581 at risk
Pneumothorax spontaneous	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Non-systematic Assessment	EG0001 events1 affected583 at risk EG0010 events0 affected581 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Non-systematic Assessment	EG0001 events1 affected583 at risk EG0010 events0 affected581 at risk
Respiratory arrest	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Miscarriage of partner	Social circumstances	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Pregnancy of partner	Social circumstances	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk
Subgaleal haematoma	Vascular disorders	MedDRA 26.0	Non-systematic Assessment	EG0000 events0 affected583 at risk EG0011 events1 affected581 at risk

ID	Title	Description
BG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.
BG001	Evobrutinib	Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Teriflunomide	Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	0	583	37	583	455	583
EG001	Evobrutinib	Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.	0	581	51	581	409	581

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 26.0	Non-systematic Assessment	EG00035 events23 affected583 at risk EG00154 events34 affected581 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 26.0	Non-systematic Assessment	EG000112 events47 affected583 at risk EG00133 events22 affected581 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 26.0	Non-systematic Assessment	EG00059 events47 affected583 at risk EG00128 events24 affected581 at risk
Nausea	Gastrointestinal disorders	MedDRA 26.0	Non-systematic Assessment	EG00039 events36 affected583 at risk EG00139 events29 affected581 at risk
Fatigue	General disorders	MedDRA 26.0	Non-systematic Assessment	EG00066 events47 affected583 at risk EG00146 events37 affected581 at risk
COVID-19	Infections and infestations	MedDRA 26.0	Non-systematic Assessment	EG000139 events121 affected583 at risk EG001119 events105 affected581 at risk
Nasopharyngitis	Infections and infestations	MedDRA 26.0	Non-systematic Assessment	EG000103 events67 affected583 at risk EG00189 events58 affected581 at risk
Respiratory tract infection viral	Infections and infestations	MedDRA 26.0	Non-systematic Assessment	EG00052 events37 affected583 at risk EG00136 events23 affected581 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 26.0	Non-systematic Assessment	EG00081 events45 affected583 at risk EG00183 events55 affected581 at risk
Urinary tract infection	Infections and infestations	MedDRA 26.0	Non-systematic Assessment	EG00046 events33 affected583 at risk EG00149 events39 affected581 at risk
Alanine aminotransferase increased	Investigations	MedDRA 26.0	Non-systematic Assessment	EG000227 events126 affected583 at risk EG001168 events99 affected581 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 26.0	Non-systematic Assessment	EG000123 events80 affected583 at risk EG00184 events61 affected581 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 26.0	Non-systematic Assessment	EG00070 events29 affected583 at risk EG00137 events31 affected581 at risk
Lipase increased	Investigations	MedDRA 26.0	Non-systematic Assessment	EG00039 events33 affected583 at risk EG00155 events33 affected581 at risk
Lymphocyte count decreased	Investigations	MedDRA 26.0	Non-systematic Assessment	EG00073 events39 affected583 at risk EG00140 events27 affected581 at risk
Neutrophil count decreased	Investigations	MedDRA 26.0	Non-systematic Assessment	EG000156 events92 affected583 at risk EG00142 events40 affected581 at risk
White blood cell count decreased	Investigations	MedDRA 26.0	Non-systematic Assessment	EG000122 events63 affected583 at risk EG00139 events23 affected581 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Non-systematic Assessment	EG00079 events61 affected583 at risk EG00163 events49 affected581 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Non-systematic Assessment	EG00040 events32 affected583 at risk EG00146 events30 affected581 at risk
Headache	Nervous system disorders	MedDRA 26.0	Non-systematic Assessment	EG000169 events103 affected583 at risk EG001198 events96 affected581 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 26.0	Non-systematic Assessment	EG00087 events84 affected583 at risk EG00138 events35 affected581 at risk