Relapsing Multiple Sclerosis
Conditions
Keywords
Evobrutinib, Teriflunomide, Aubagio®, Relapsing Multiple Sclerosis
Brief summary
The study is to evaluate the efficacy and safety of evobrutinib administered orally twice daily versus Teriflunomide (Aubagio®), administered orally once daily in participants with Relapsing Multiple Sclerosis (RMS). Participants who complete the double-blind treatment period (DBTP) and double-blind extension period (DBEP) prior to approval of a separate long-term follow-up study in their country will get an option for evobrutinib treatment continuation through a 96-week open-label extension (OLE) period.
Interventions
DRUGTeriflunomide
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 and followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in open label extension (OLE) period.
DRUGEvobrutinib
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 and followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in open label extension (OLE) period.
Sponsors
EMD Serono Research & Development Institute, Inc.
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Participants are diagnosed with RMS (relapsing-remitting multiple sclerosis \[RRMS\] or secondary progressive multiple sclerosis \[SPMS\] with relapses) in accordance with 2017 Revised McDonald criteria (Thompson 2018) * Participants with one or more documented relapses within the 2 years before Screening with either: a. one relapse which occurred within the last year prior to randomization, OR b. the presence of at least 1 gadolinium-enhancing (Gd+) T1 lesion within 6 months prior to randomization * Participants have Expanded Disability Status Scale (EDSS) score of 0 to 5.5 at Screening and Baseline (Day 1). Participants with an EDSS score \<= 2 at Screening and Baseline (Day 1) are only eligible for participation if their disease duration (time since onset of symptoms) is no more than 10 years * Participants are neurologically stable for \>= 30 days prior to both screening and baseline (Day 1) * Female participants must be neither pregnant nor breast-feeding or must lack child-bearing potential (as defined by either: post-menopausal or surgically sterile), or use an effective method of contraception for the duration of the study and at least 2 years after study intervention due to the long elimination period for teriflunomide of 2 years, unless the participant undergoes an accelerated elimination procedure * Male participants must refrain from donating sperm and/or abstain from intercourse with women of child-bearing potential or use an effective method of contraception for the duration of the study and at least 2 years after study intervention due to the long elimination period for teriflunomide of 2 years, unless the participant undergoes an accelerated elimination procedure * Participants have given written informed consent prior to any study-related procedure * Other protocol defined inclusion criteria could apply.
Exclusion criteria
* Participants diagnosed with Progressive MS, in accordance with the 2017 Revised McDonald criteria as follows: a). Participants with Primary Progressive MS. b). Participants with secondary progressive MS without evidence of relapse * Disease duration more than (\>) 10 years in participants with an EDSS =\< 2.0 at screening and Baseline (Day 1) * Immunologic disorder other than MS, or any other condition requiring oral, intravenous (IV) , intramuscular, or intra-articular corticosteroid therapy, with the exception of well-controlled Type 2 diabetes mellitus or well controlled thyroid disease * Other protocol defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Double Blind Treatment Period (DBTP) and Double Blind Extension (DBE) Period: Annualized Relapse Rate (ARR) | From baseline to 172 weeks | 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). |
| Open Label Extension (OLE) Period: Number of Participants With Adverse Events (AEs) and Serious AEs | From OLE Baseline (DBTP Week 96) to OLE Week 52 | Adverse event (AE): Any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the study drug. Therefore, an AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| DBTP Period: Neurofilament Light Chain Concentration (NfL) at Week 12 | Week 12 | NfL is a biomarker of neuro-axonal damage whose concentration was assessed in blood at Week 12. |
| DBTP and DBE Period: Percentage of Participants Without 12-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS) | Week 96 and Week 156 (combined DBTP and DBE period) | 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. |
| DBTP and DBE Period: Percentage of Participants Without 24-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS) | Week 96 and Week 156 (combined DBTP and DBE periods) | 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. |
| DBTP and DBE Period: Percentage of Participants With 24-Week Confirmed Disability Improvement (CDI) as Measured by Expanded Disability Status Scale (EDSS) | Week 96 and Week 156 (combined DBTP and DBE periods) | 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. |
| 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 | Baseline, Week 48, Week 96, Week 120, Week 144 and Week 156 (combined DBTP and DBE periods) | 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). |
| 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 | Baseline, Week 48, Week 96, Week 120, Week 144 and Week 156 (combined DBTP and DBE periods) | 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). |
| DBTP and DBE Periods: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Adverse Events of Special Interest (AESIs) | From baseline to 176 weeks | 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. |
| DBTP and DBE Periods: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | From baseline to 176 weeks | 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. |
| DBTP and DBE Periods: Change From Baseline in Vital Signs: Diastolic Blood Pressure and Systolic Blood Pressure | From baseline to 176 weeks | 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 176 weeks were reported. |
| DBTP and DBE Periods: Change From Baseline in Vital Signs: Pulse Rate | From baseline to 176 weeks | 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 baseline up to 176 weeks was reported. |
| DBTP and DBE Periods: Change From Baseline in Vital Signs: Respiratory Rate | From baseline to 176 weeks | 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 176 weeks was reported. |
| DBTP and DBE Periods: Change From Baseline in Vital Signs: Weight | From baseline to 176 weeks | Changes in vital signs: weight from baseline up to 176 weeks was reported. |
| DBTP and DBE Periods: Change From Baseline in Vital Signs: Temperature | From baseline to 176 weeks | 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 176 weeks was reported. |
| DBTP and DBE Periods: Change From Baseline in Electrocardiograms (ECGs) Parameter: Heart Rate | From baseline to 176 weeks | Heart rate was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions. Changes in ECG parameter: heart rate from baseline up to 176 weeks was reported. |
| DBTP and DBE Periods: Change From Baseline in Electrocardiograms (ECGs) Parameters: QT Interval - Fridericia's Correction Formula, PR Interval and QRS Duration | From baseline to 176 weeks | 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 ECG parameter: QT Interval - Fridericia's Correction Formula, PR Interval and QRS Duration from baseline up to 176 weeks were reported. |
| DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Hemoglobin and Erythrocytes Mean Corpuscular Hemoglobin (HGB) Concentration | From baseline to 176 weeks | 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 176 weeks were reported. |
| DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes | From baseline to 176 weeks | 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 176 weeks were reported. |
| DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Hematocrit | From baseline to 176 weeks | 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 176 weeks was reported. |
| DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin | From baseline to 176 weeks | 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 176 weeks was reported. |
| DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume | From baseline to 176 weeks | 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 176 weeks was reported. |
| DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Bilirubin and Creatinine | From baseline to 176 weeks | 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 176 weeks were reported. |
| DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase | From baseline to 176 weeks | 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 176 weeks were reported. |
| DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium | From baseline to 176 weeks | 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 176 weeks were reported. |
| DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Total Protein and Albumin | From baseline to 176 weeks | 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 176 weeks were reported. |
| DBTP and DBE Periods: Change From Baseline in Biochemistry Parameter: Glomerular Filtration Rate | From baseline to 176 weeks | 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 176 weeks was reported. The Glomerular Filtration Rate will be measured as milliliter per minute per 1.73 square meter (mL/min/1.73m\^2). |
| DBTP and DBE Periods: Change From Baseline in Urinalyses Parameter: Potential of Hydrogen (pH) of Urine | From baseline to 176 weeks | 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 176 weeks was reported. |
| DBTP and DBE Periods: Change From Baseline in Urinalyses Parameter: Specific Gravity of Urine | From baseline to 176 weeks | 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 176 weeks was reported. |
| DBTP and DBE Periods: Absolute Concentrations of Immunoglobulin (Ig) Levels | At Week 176 | Absolute Concentrations serum levels of IgG, IgA, IgM were assessed. |
| DBTP and DBE Periods: Change From Baseline in Immunoglobulin (Ig) Levels | Baseline to 176 weeks | Change from baseline serum levels of IgG, IgA, IgM were assessed. |
| OLE Period: Annualized Relapse Rate (ARR) | From OLE baseline (DBTP Week 96) to OLE Week 52 | 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, AEs, and preceded by a stable or improving neurological state for more than or equal to \[\>=\] 30 days). |
| OLE Period: Percentage of Participants Without 24-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS) | From OLE baseline (DBTP Week 96) to OLE Week 52 | 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). |
| OLE Period: Percentage of Participants With 24-Week Confirmed Disability Improvement (CDI) as Measured by Expanded Disability Status Scale (EDSS) | From OLE baseline (DBTP Week 96) to OLE Week 52 | 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). |
| OLE Period: Symbol Digit Modalities Test (SDMT) | Assessed from OLE baseline to OLE Week 96; OLE Week 48 were reported for Participants 1 and 2 and OLE Week 12 were reported for Participant 3 | The SDMT is a test of information 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 indicated improvement and lower scores indicated worsening. Participant wise data was reported for this outcome measure. |
| OLE Period: Change From Baseline in PROMISnq Physical Function (PF) Multiple Sclerosis (MS) 15a at Week 52 | OLE Baseline (DBTP Week 96), OLE Week 52 | 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 ranges from 10 to 65. Higher T-scores represent higher physical function. Participant wise data was reported for this outcome measure. |
| OLE Period: Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue (MS) 8a Score at Week 52 | OLE baseline (DBTP Week 96), OLE Week 52 | 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 general, T-scores have a mean of 50, standard deviation of 10, and range from 33 to 85. Higher T-scores represent higher fatigue. Participant wise data was reported for this outcome measure. |
| OLE Period: Number of Participants With Abnormalities in Laboratory Parameters | From OLE baseline (DBTP Week 96) to OLE Week 52 | Laboratory investigation included hematology, biochemistry and coagulation. The number of participants with abnormalities in laboratory parameters were reported. |
| DBTP and DBE Period: Total Number of T1 Gadolinium-positive (Gd+) Lesions | From baseline to 176 weeks | Analysis of Gadolinium-positive T1 lesions was done using magnetic resonance imaging (MRI) scans. |
| OLE Period: Number of Participants With Abnormalities in Electrocardiograms (ECGs) Findings | From OLE baseline (DBTP Week 96) to OLE Week 52 | ECG recordings included, heart rate, PR interval and QRS duration. ECG recordings were obtained after the participants have rested for at least 5 minutes in supine position. The number of participants with abnormalities in ECG findings were reported. |
| OLE Period: Number of New or Enlarging T2 Lesions | From OLE baseline (DBTP Week 96) to OLE Week 52 | Analysis of number of new or enlarging T2 lesions 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. Participant wise data was reported for this outcome measure. |
| OLE Period: Change From Baseline in T2 Lesion Volume | From OLE baseline (DBTP Week 96) to OLE Week 52 | Change from baseline in T2 lesion volume was reported. Participant wise data was reported for this outcome measure. |
| OLE Period: Number of Participants With Abnormalities in Vital Signs | From OLE baseline (DBTP Week 96) to OLE Week 52 | Vital signs included temperature, pulse rate, respiration rate and blood pressure and weight (taken after 5 minutes in the sitting position). The number of participants with abnormalities in vital signs were reported. |
| DBTP and DBE Period: New or Enlarging T2 Lesions Rate | From baseline to 176 weeks | 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. |
Countries
Argentina, Australia, Austria, Belgium, Bosnia and Herzegovina, Bulgaria, Canada, Colombia, Croatia, Czechia, Estonia, Finland, France, Georgia, Germany, Hong Kong, Hungary, India, Israel, Italy, Mexico, Netherlands, Poland, Russia, Serbia, South Korea, Spain, Taiwan, Ukraine, United Kingdom, United States
Participant flow
Pre-assignment details
3 participants were enrolled in the Open Label Extension (OLE) Period after Double Blind Treatment Period (DBTP) Week 96 and they did not enter Double Blind Extension (DBE) period.
Participants by arm
| Arm | Count |
|---|---|
| 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 and followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in open label extension (OLE) period. | 564 |
| 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 and followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in open label extension (OLE) period. | 560 |
| Total | 1,124 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-blind Extension: 96 Weeks | Adverse Event | 2 | 0 |
| Double-blind Extension: 96 Weeks | Lack of Efficacy | 1 | 2 |
| Double-blind Extension: 96 Weeks | Lost to Follow-up | 0 | 1 |
| Double-blind Extension: 96 Weeks | Other Reason | 3 | 9 |
| Double-blind Extension: 96 Weeks | Withdrawal by Subject | 0 | 1 |
| Double-blind Treatment Period: 156 Weeks | Adverse Event | 56 | 72 |
| Double-blind Treatment Period: 156 Weeks | Death | 1 | 1 |
| Double-blind Treatment Period: 156 Weeks | Lack of Efficacy | 19 | 23 |
| Double-blind Treatment Period: 156 Weeks | Lost to Follow-up | 6 | 5 |
| Double-blind Treatment Period: 156 Weeks | Other Reason | 24 | 14 |
| Double-blind Treatment Period: 156 Weeks | Protocol Non-Compliance | 5 | 5 |
| Double-blind Treatment Period: 156 Weeks | Randomized, but not treated | 1 | 1 |
| Double-blind Treatment Period: 156 Weeks | Withdrawal by Subject | 56 | 55 |
| Open Label Extension: 96 Weeks | Study Termination | 0 | 3 |
Baseline characteristics
| Characteristic | Evobrutinib | Total | Teriflunomide |
|---|---|---|---|
| Age, Continuous | 37 Years STANDARD_DEVIATION 9.6 | 38 Years STANDARD_DEVIATION 9.5 | 38 Years STANDARD_DEVIATION 9.5 |
| Race/Ethnicity, Customized Ethnicity-Hispanic or Latino | 63 Participants | 123 Participants | 60 Participants |
| Race/Ethnicity, Customized Ethnicity-Not Hispanic or Latino | 497 Participants | 1001 Participants | 504 Participants |
| Race/Ethnicity, Customized Race-American Indian or Alaska Native | 13 Participants | 19 Participants | 6 Participants |
| Race/Ethnicity, Customized Race-Asian | 16 Participants | 26 Participants | 10 Participants |
| Race/Ethnicity, Customized Race-Black or African American | 4 Participants | 6 Participants | 2 Participants |
| Race/Ethnicity, Customized Race-Multiple | 2 Participants | 7 Participants | 5 Participants |
| Race/Ethnicity, Customized Race-Other | 1 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Race-Unknown or Not Reported | 5 Participants | 8 Participants | 3 Participants |
| Race/Ethnicity, Customized Race-White | 519 Participants | 1055 Participants | 536 Participants |
| Sex: Female, Male Female | 377 Participants | 751 Participants | 374 Participants |
| Sex: Female, Male Male | 183 Participants | 373 Participants | 190 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 563 | 1 / 559 |
| other Total, other adverse events | 409 / 563 | 361 / 559 |
| serious Total, serious adverse events | 33 / 563 | 45 / 559 |
Outcome results
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).
Time frame: From baseline to 172 weeks
Population: Full Analysis Set (FAS) included all participants who were randomized to study treatment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Teriflunomide | Double Blind Treatment Period (DBTP) and Double Blind Extension (DBE) Period: Annualized Relapse Rate (ARR) | 0.13 relapses per year |
| Evobrutinib | Double Blind Treatment Period (DBTP) and Double Blind Extension (DBE) Period: Annualized Relapse Rate (ARR) | 0.14 relapses per year |
Primary
Open Label Extension (OLE) Period: Number of Participants With Adverse Events (AEs) and Serious AEs
Adverse event (AE): Any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the study drug. Therefore, an AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to 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.
Time frame: From OLE Baseline (DBTP Week 96) to OLE Week 52
Population: Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Teriflunomide | Open Label Extension (OLE) Period: Number of Participants With Adverse Events (AEs) and Serious AEs | Participants with AEs | 1 Participants |
| Teriflunomide | Open Label Extension (OLE) Period: Number of Participants With Adverse Events (AEs) and Serious AEs | Participants with Serious AEs | 0 Participants |
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).
Time frame: Baseline, Week 48, Week 96, Week 120, Week 144 and Week 156 (combined DBTP and DBE periods)
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Teriflunomide | 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 | Week 156 | 0.72 units on a scale |
| Teriflunomide | 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 | Week 48 | -1.39 units on a scale |
| Teriflunomide | 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 | Week 96 | -1.60 units on a scale |
| Teriflunomide | 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 | Week 120 | -1.44 units on a scale |
| Teriflunomide | 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 | Week 144 | -1.88 units on a scale |
| Evobrutinib | 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 | Week 144 | -0.98 units on a scale |
| Evobrutinib | 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 | Week 120 | -1.32 units on a scale |
| Evobrutinib | 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 | Week 48 | -1.82 units on a scale |
| Evobrutinib | 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 | Week 156 | -0.21 units on a scale |
| Evobrutinib | 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 | Week 96 | -2.14 units on a scale |
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).
Time frame: Baseline, Week 48, Week 96, Week 120, Week 144 and Week 156 (combined DBTP and DBE periods)
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Teriflunomide | 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 | Week 96 | -0.76 units on a scale |
| Teriflunomide | 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 | Week 144 | -1.04 units on a scale |
| Teriflunomide | 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 | Week 120 | -0.29 units on a scale |
| Teriflunomide | 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 | Week 156 | -1.61 units on a scale |
| Teriflunomide | 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 | Week 48 | -0.30 units on a scale |
| Evobrutinib | 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 | Week 156 | -1.44 units on a scale |
| Evobrutinib | 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 | Week 48 | 0.05 units on a scale |
| Evobrutinib | 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 | Week 96 | -0.14 units on a scale |
| Evobrutinib | 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 | Week 120 | -0.25 units on a scale |
| Evobrutinib | 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 | Week 144 | -0.70 units on a scale |
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.
Time frame: From baseline to 176 weeks
Population: Full Analysis Set (FAS) included all participants who were randomized to study treatment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Teriflunomide | DBTP and DBE Period: New or Enlarging T2 Lesions Rate | 5.78 lesions per year |
| Evobrutinib | DBTP and DBE Period: New or Enlarging T2 Lesions Rate | 5.45 lesions per year |
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.
Time frame: Week 96 and Week 156 (combined DBTP and DBE periods)
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Teriflunomide | DBTP and DBE Period: Percentage of Participants With 24-Week Confirmed Disability Improvement (CDI) as Measured by Expanded Disability Status Scale (EDSS) | Week 156 | 8.8 percentage of participants |
| Teriflunomide | DBTP and DBE Period: Percentage of Participants With 24-Week Confirmed Disability Improvement (CDI) as Measured by Expanded Disability Status Scale (EDSS) | Week 96 | 7.9 percentage of participants |
| Evobrutinib | DBTP and DBE Period: Percentage of Participants With 24-Week Confirmed Disability Improvement (CDI) as Measured by Expanded Disability Status Scale (EDSS) | Week 96 | 9.4 percentage of participants |
| Evobrutinib | DBTP and DBE Period: Percentage of Participants With 24-Week Confirmed Disability Improvement (CDI) as Measured by Expanded Disability Status Scale (EDSS) | Week 156 | 10.1 percentage of participants |
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.
Time frame: Week 96 and Week 156 (combined DBTP and DBE period)
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Teriflunomide | DBTP and DBE Period: Percentage of Participants Without 12-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS) | Week 96 | 91.0 percentage of participants |
| Teriflunomide | DBTP and DBE Period: Percentage of Participants Without 12-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS) | Week 156 | 86.0 percentage of participants |
| Evobrutinib | DBTP and DBE Period: Percentage of Participants Without 12-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS) | Week 96 | 91.3 percentage of participants |
| Evobrutinib | DBTP and DBE Period: Percentage of Participants Without 12-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS) | Week 156 | 87.9 percentage of participants |
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.
Time frame: Week 96 and Week 156 (combined DBTP and DBE periods)
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Teriflunomide | DBTP and DBE Period: Percentage of Participants Without 24-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS) | Week 96 | 94.3 percentage of participants |
| Teriflunomide | DBTP and DBE Period: Percentage of Participants Without 24-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS) | Week 156 | 92.3 percentage of participants |
| Evobrutinib | DBTP and DBE Period: Percentage of Participants Without 24-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS) | Week 96 | 92.7 percentage of participants |
| Evobrutinib | DBTP and DBE Period: Percentage of Participants Without 24-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS) | Week 156 | 92.1 percentage of participants |
Secondary
DBTP and DBE Periods: Absolute Concentrations of Immunoglobulin (Ig) Levels
Absolute Concentrations serum levels of IgG, IgA, IgM were assessed.
Time frame: At Week 176
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teriflunomide | DBTP and DBE Periods: Absolute Concentrations of Immunoglobulin (Ig) Levels | IgA | 1.750 gram per liter (g/L) | Standard Deviation 0.7987 |
| Teriflunomide | DBTP and DBE Periods: Absolute Concentrations of Immunoglobulin (Ig) Levels | IgG | 9.693 gram per liter (g/L) | Standard Deviation 2.1096 |
| Teriflunomide | DBTP and DBE Periods: Absolute Concentrations of Immunoglobulin (Ig) Levels | IgM | 1.101 gram per liter (g/L) | Standard Deviation 0.6096 |
| Evobrutinib | DBTP and DBE Periods: Absolute Concentrations of Immunoglobulin (Ig) Levels | IgA | 2.503 gram per liter (g/L) | Standard Deviation 1.0582 |
| Evobrutinib | DBTP and DBE Periods: Absolute Concentrations of Immunoglobulin (Ig) Levels | IgG | 10.529 gram per liter (g/L) | Standard Deviation 2.2363 |
| Evobrutinib | DBTP and DBE Periods: Absolute Concentrations of Immunoglobulin (Ig) Levels | IgM | 1.181 gram per liter (g/L) | Standard Deviation 0.6619 |
Secondary
DBTP and DBE Periods: Change From Baseline in Biochemistry Parameter: 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 176 weeks was reported. The Glomerular Filtration Rate will be measured as milliliter per minute per 1.73 square meter (mL/min/1.73m\^2).
Time frame: From baseline to 176 weeks
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameter: Glomerular Filtration Rate | -3.3 mL/min/1.73m^2 | Standard Deviation 13.82 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameter: Glomerular Filtration Rate | -5.6 mL/min/1.73m^2 | Standard Deviation 13.54 |
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 176 weeks were reported.
Time frame: From baseline to 176 weeks
Population: 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 and number analyzed= participants who were evaluable for the specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase | Alkaline Phosphatase | 4.20 units per liter (U/L) | Standard Deviation 23.289 |
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase | Lipase | -2.5 units per liter (U/L) | Standard Deviation 33.36 |
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase | Alanine Aminotransferase | 4.06 units per liter (U/L) | Standard Deviation 23.308 |
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase | Gamma Glutamyl Transferase | 4.28 units per liter (U/L) | Standard Deviation 21.091 |
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase | Amylase | -0.5 units per liter (U/L) | Standard Deviation 17.04 |
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase | Lactate Dehydrogenase | 6.16 units per liter (U/L) | Standard Deviation 28.235 |
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase | Aspartate Aminotransferase | 2.32 units per liter (U/L) | Standard Deviation 18.19 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase | Lactate Dehydrogenase | -4.53 units per liter (U/L) | Standard Deviation 26.014 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase | Aspartate Aminotransferase | 6.49 units per liter (U/L) | Standard Deviation 64.249 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase | Alanine Aminotransferase | 8.55 units per liter (U/L) | Standard Deviation 52.866 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase | Alkaline Phosphatase | 7.65 units per liter (U/L) | Standard Deviation 20.252 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase | Amylase | 2.8 units per liter (U/L) | Standard Deviation 16.84 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase | Lipase | 3.5 units per liter (U/L) | Standard Deviation 17.33 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase | Gamma Glutamyl Transferase | 5.51 units per liter (U/L) | Standard Deviation 40.098 |
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 176 weeks were reported.
Time frame: From baseline to 176 weeks
Population: 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 and number analyzed= participants who were evaluable for the specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Bilirubin and Creatinine | Bilirubin | -0.08 micromoles per liter (mcmol/L) | Standard Deviation 4.792 |
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Bilirubin and Creatinine | Creatinine | 0.6 micromoles per liter (mcmol/L) | Standard Deviation 12.76 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Bilirubin and Creatinine | Bilirubin | 0.15 micromoles per liter (mcmol/L) | Standard Deviation 4.792 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Bilirubin and Creatinine | Creatinine | 2.4 micromoles per liter (mcmol/L) | Standard Deviation 8.67 |
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 176 weeks were reported.
Time frame: From baseline to 176 weeks
Population: 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 and number analyzed= participants who were evaluable for the specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium | Calcium | 0.004 millimole per liter (mmol/L) | Standard Deviation 0.1139 |
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium | Chloride | 1.8 millimole per liter (mmol/L) | Standard Deviation 3.42 |
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium | Potassium | 0.0320 millimole per liter (mmol/L) | Standard Deviation 0.43741 |
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium | Urea Nitrogen | 0.222 millimole per liter (mmol/L) | Standard Deviation 1.2668 |
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium | Magnesium | 0.004 millimole per liter (mmol/L) | Standard Deviation 0.0682 |
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium | Sodium | 0.9128 millimole per liter (mmol/L) | Standard Deviation 2.34334 |
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium | Bicarbonate | 0.05 millimole per liter (mmol/L) | Standard Deviation 2.561 |
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium | Glucose | 0.06 millimole per liter (mmol/L) | Standard Deviation 0.928 |
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium | Corrected Calcium | 0.0297 millimole per liter (mmol/L) | Standard Deviation 0.09428 |
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium | Phosphate | -0.053 millimole per liter (mmol/L) | Standard Deviation 0.2048 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium | Corrected Calcium | 0.0317 millimole per liter (mmol/L) | Standard Deviation 0.09071 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium | Sodium | 0.7904 millimole per liter (mmol/L) | Standard Deviation 2.2899 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium | Potassium | 0.0893 millimole per liter (mmol/L) | Standard Deviation 0.42341 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium | Calcium | -0.002 millimole per liter (mmol/L) | Standard Deviation 0.1029 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium | Magnesium | 0.002 millimole per liter (mmol/L) | Standard Deviation 0.0656 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium | Glucose | 0.25 millimole per liter (mmol/L) | Standard Deviation 1.146 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium | Chloride | 1.7 millimole per liter (mmol/L) | Standard Deviation 2.95 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium | Urea Nitrogen | 0.114 millimole per liter (mmol/L) | Standard Deviation 1.2654 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium | Phosphate | -0.026 millimole per liter (mmol/L) | Standard Deviation 0.1724 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium | Bicarbonate | 0.04 millimole per liter (mmol/L) | Standard Deviation 2.725 |
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 176 weeks were reported.
Time frame: From baseline to 176 weeks
Population: 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 and number analyzed= participants who were evaluable for the specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Total Protein and Albumin | Total protein | -1.26 gram per liter (g/L) | Standard Deviation 4.865 |
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Total Protein and Albumin | Albumin | -1.28 gram per liter (g/L) | Standard Deviation 3.52 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Total Protein and Albumin | Total protein | -0.47 gram per liter (g/L) | Standard Deviation 4.417 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Total Protein and Albumin | Albumin | -1.67 gram per liter (g/L) | Standard Deviation 3.284 |
Secondary
DBTP and DBE Periods: Change From Baseline in Electrocardiograms (ECGs) Parameter: Heart Rate
Heart rate was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions. Changes in ECG parameter: heart rate from baseline up to 176 weeks was reported.
Time frame: From baseline to 176 weeks
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Electrocardiograms (ECGs) Parameter: Heart Rate | 3.0 beats per minute | Standard Deviation 10.9 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Electrocardiograms (ECGs) Parameter: Heart Rate | -0.1 beats per minute | Standard Deviation 12.55 |
Secondary
DBTP and DBE Periods: Change From Baseline in Electrocardiograms (ECGs) Parameters: 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 ECG parameter: QT Interval - Fridericia's Correction Formula, PR Interval and QRS Duration from baseline up to 176 weeks were reported.
Time frame: From baseline to 176 weeks
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Electrocardiograms (ECGs) Parameters: QT Interval - Fridericia's Correction Formula, PR Interval and QRS Duration | QT Interval - Fridericia's Correction Formula | -2.77 milliseconds (msec) | Standard Deviation 16.005 |
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Electrocardiograms (ECGs) Parameters: QT Interval - Fridericia's Correction Formula, PR Interval and QRS Duration | PR Interval | -5.2 milliseconds (msec) | Standard Deviation 14.31 |
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Electrocardiograms (ECGs) Parameters: QT Interval - Fridericia's Correction Formula, PR Interval and QRS Duration | QRS Duration | -3.7 milliseconds (msec) | Standard Deviation 7.48 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Electrocardiograms (ECGs) Parameters: QT Interval - Fridericia's Correction Formula, PR Interval and QRS Duration | QT Interval - Fridericia's Correction Formula | -1.37 milliseconds (msec) | Standard Deviation 12.053 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Electrocardiograms (ECGs) Parameters: QT Interval - Fridericia's Correction Formula, PR Interval and QRS Duration | PR Interval | -2.5 milliseconds (msec) | Standard Deviation 14.65 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Electrocardiograms (ECGs) Parameters: QT Interval - Fridericia's Correction Formula, PR Interval and QRS Duration | QRS Duration | -1.5 milliseconds (msec) | Standard Deviation 10.82 |
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 176 weeks was reported.
Time frame: From baseline to 176 weeks
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin | -0.61 picogram (pg) | Standard Deviation 1.588 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin | -0.62 picogram (pg) | Standard Deviation 1.956 |
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 176 weeks was reported.
Time frame: From baseline to 176 weeks
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume | -1.42 femtoliters | Standard Deviation 5.999 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume | -1.75 femtoliters | Standard Deviation 4.895 |
Secondary
DBTP and DBE Periods: Change From Baseline in Hematology Parameter: 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 176 weeks was reported.
Time frame: From baseline to 176 weeks
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Hematocrit | -0.0069 percentage of cells | Standard Deviation 0.03359 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Hematocrit | -0.0076 percentage of cells | Standard Deviation 0.03238 |
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 176 weeks were reported.
Time frame: From baseline to 176 weeks
Population: 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 and number analyzed= participants who were evaluable for the specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Hemoglobin and Erythrocytes Mean Corpuscular Hemoglobin (HGB) Concentration | Hemoglobin | -3.5 gram per liter (g/L) | Standard Deviation 10.74 |
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Hemoglobin and Erythrocytes Mean Corpuscular Hemoglobin (HGB) Concentration | Erythrocytes Mean Corpuscular HGB Concentration | -2.7 gram per liter (g/L) | Standard Deviation 12.43 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Hemoglobin and Erythrocytes Mean Corpuscular Hemoglobin (HGB) Concentration | Hemoglobin | -2.8 gram per liter (g/L) | Standard Deviation 11.34 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Hemoglobin and Erythrocytes Mean Corpuscular Hemoglobin (HGB) Concentration | Erythrocytes Mean Corpuscular HGB Concentration | -1.0 gram per liter (g/L) | Standard Deviation 11.96 |
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 176 weeks were reported.
Time frame: From baseline to 176 weeks
Population: 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 and number analyzed= participants who were evaluable for the specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes | Platelets | -4.8 10^9 cells per liter | Standard Deviation 47.09 |
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes | Leukocytes | -0.17 10^9 cells per liter | Standard Deviation 2.165 |
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes | Neutrophils | -0.316 10^9 cells per liter | Standard Deviation 1.8846 |
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes | Eosinophils | 0.0510 10^9 cells per liter | Standard Deviation 0.15999 |
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes | Basophils | -0.0009 10^9 cells per liter | Standard Deviation 0.03657 |
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes | Monocytes | 0.0785 10^9 cells per liter | Standard Deviation 0.18171 |
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes | Lymphocytes | -0.0307 10^9 cells per liter | Standard Deviation 0.58566 |
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes | Reticulocytes | 0.488 10^9 cells per liter | Standard Deviation 20.2014 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes | Reticulocytes | -0.827 10^9 cells per liter | Standard Deviation 17.6824 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes | Platelets | 8.8 10^9 cells per liter | Standard Deviation 53.83 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes | Basophils | -0.0003 10^9 cells per liter | Standard Deviation 0.03786 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes | Leukocytes | -0.09 10^9 cells per liter | Standard Deviation 1.958 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes | Lymphocytes | -0.0401 10^9 cells per liter | Standard Deviation 0.58108 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes | Neutrophils | -0.210 10^9 cells per liter | Standard Deviation 1.8356 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes | Monocytes | 0.0656 10^9 cells per liter | Standard Deviation 0.17816 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes | Eosinophils | 0.0203 10^9 cells per liter | Standard Deviation 0.15853 |
Secondary
DBTP and DBE Periods: Change From Baseline in Immunoglobulin (Ig) Levels
Change from baseline serum levels of IgG, IgA, IgM were assessed.
Time frame: Baseline to 176 weeks
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Immunoglobulin (Ig) Levels | IgA | -0.262 gram per liter (g/L) | Standard Deviation 0.3572 |
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Immunoglobulin (Ig) Levels | IgG | -0.733 gram per liter (g/L) | Standard Deviation 1.4414 |
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Immunoglobulin (Ig) Levels | IgM | -0.165 gram per liter (g/L) | Standard Deviation 0.2979 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Immunoglobulin (Ig) Levels | IgA | 0.483 gram per liter (g/L) | Standard Deviation 0.532 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Immunoglobulin (Ig) Levels | IgG | 0.105 gram per liter (g/L) | Standard Deviation 1.4556 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Immunoglobulin (Ig) Levels | IgM | -0.187 gram per liter (g/L) | Standard Deviation 0.2794 |
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 176 weeks was reported.
Time frame: From baseline to 176 weeks
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Urinalyses Parameter: Potential of Hydrogen (pH) of Urine | -0.08 pH | Standard Deviation 0.886 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Urinalyses Parameter: Potential of Hydrogen (pH) of Urine | 0.01 pH | Standard Deviation 0.913 |
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 176 weeks was reported.
Time frame: From baseline to 176 weeks
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Urinalyses Parameter: Specific Gravity of Urine | 0.0006 Kilogram per cubic meter | Standard Deviation 0.03891 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Urinalyses Parameter: Specific Gravity of Urine | 0.0011 Kilogram per cubic meter | Standard Deviation 0.02189 |
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 176 weeks were reported.
Time frame: From baseline to 176 weeks
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Vital Signs: Diastolic Blood Pressure and Systolic Blood Pressure | Systolic Blood Pressure | 2.6 millimeter of mercury (mmHg) | Standard Deviation 11.18 |
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Vital Signs: Diastolic Blood Pressure and Systolic Blood Pressure | Diastolic Blood Pressure | 1.8 millimeter of mercury (mmHg) | Standard Deviation 8.35 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Vital Signs: Diastolic Blood Pressure and Systolic Blood Pressure | Systolic Blood Pressure | 0.2 millimeter of mercury (mmHg) | Standard Deviation 10.83 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Vital Signs: Diastolic Blood Pressure and Systolic Blood Pressure | Diastolic Blood Pressure | 0.0 millimeter of mercury (mmHg) | Standard Deviation 8.67 |
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 baseline up to 176 weeks was reported.
Time frame: From baseline to 176 weeks
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Vital Signs: Pulse Rate | 2.6 beats per minute | Standard Deviation 10.22 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Vital Signs: Pulse Rate | 1.9 beats per minute | Standard Deviation 9.68 |
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 176 weeks was reported.
Time frame: From baseline to 176 weeks
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Vital Signs: Respiratory Rate | -0.1 breaths per minute | Standard Deviation 1.76 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Vital Signs: Respiratory Rate | -0.2 breaths per minute | Standard Deviation 1.88 |
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 176 weeks was reported.
Time frame: From baseline to 176 weeks
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Vital Signs: Temperature | 0.00 degree Celsius | Standard Deviation 0.326 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Vital Signs: Temperature | 0.02 degree Celsius | Standard Deviation 0.319 |
Secondary
DBTP and DBE Periods: Change From Baseline in Vital Signs: Weight
Changes in vital signs: weight from baseline up to 176 weeks was reported.
Time frame: From baseline to 176 weeks
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teriflunomide | DBTP and DBE Periods: Change From Baseline in Vital Signs: Weight | -0.21 kilograms (kg) | Standard Deviation 5.867 |
| Evobrutinib | DBTP and DBE Periods: Change From Baseline in Vital Signs: Weight | 0.48 kilograms (kg) | Standard Deviation 5.49 |
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.
Time frame: From baseline to 176 weeks
Population: Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Teriflunomide | DBTP and DBE Periods: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Adverse Events of Special Interest (AESIs) | Participants with TEAEs | 485 Participants |
| Teriflunomide | DBTP and DBE Periods: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Adverse Events of Special Interest (AESIs) | Participants with AESIs | 120 Participants |
| Evobrutinib | DBTP and DBE Periods: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Adverse Events of Special Interest (AESIs) | Participants with TEAEs | 482 Participants |
| Evobrutinib | DBTP and DBE Periods: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Adverse Events of Special Interest (AESIs) | Participants with AESIs | 117 Participants |
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.
Time frame: From baseline to 176 weeks
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Teriflunomide | DBTP and DBE Periods: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Participants with Grade 2 | 349 Participants |
| Teriflunomide | DBTP and DBE Periods: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Participants with Grade 4 | 3 Participants |
| Teriflunomide | DBTP and DBE Periods: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Participants with Grade 3 | 82 Participants |
| Teriflunomide | DBTP and DBE Periods: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Participants with Grade 5 | 1 Participants |
| Teriflunomide | DBTP and DBE Periods: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Participants with Grade 1 | 50 Participants |
| Evobrutinib | DBTP and DBE Periods: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Participants with Grade 5 | 1 Participants |
| Evobrutinib | DBTP and DBE Periods: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Participants with Grade 1 | 56 Participants |
| Evobrutinib | DBTP and DBE Periods: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Participants with Grade 2 | 327 Participants |
| Evobrutinib | DBTP and DBE Periods: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Participants with Grade 3 | 88 Participants |
| Evobrutinib | DBTP and DBE Periods: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Participants with Grade 4 | 10 Participants |
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.
Time frame: From baseline to 176 weeks
Population: Full Analysis Set (FAS) included all participants who were randomized to study treatment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Teriflunomide | DBTP and DBE Period: Total Number of T1 Gadolinium-positive (Gd+) Lesions | 0.35 lesions per scan |
| Evobrutinib | DBTP and DBE Period: Total Number of T1 Gadolinium-positive (Gd+) Lesions | 0.52 lesions per scan |
Secondary
DBTP Period: Neurofilament Light Chain Concentration (NfL) at Week 12
NfL is a biomarker of neuro-axonal damage whose concentration was assessed in blood at Week 12.
Time frame: Week 12
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Teriflunomide | DBTP Period: Neurofilament Light Chain Concentration (NfL) at Week 12 | 12.90 nanogram per liter (ng/L) |
| Evobrutinib | DBTP Period: Neurofilament Light Chain Concentration (NfL) at Week 12 | 12.88 nanogram per liter (ng/L) |
Secondary
OLE 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, AEs, and preceded by a stable or improving neurological state for more than or equal to \[\>=\] 30 days).
Time frame: From OLE baseline (DBTP Week 96) to OLE Week 52
Population: Full Analysis Set (FAS) included all participants who were randomized to study treatment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Teriflunomide | OLE Period: Annualized Relapse Rate (ARR) | NA relapses per year |
Secondary
OLE Period: Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue (MS) 8a Score at Week 52
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 general, T-scores have a mean of 50, standard deviation of 10, and range from 33 to 85. Higher T-scores represent higher fatigue. Participant wise data was reported for this outcome measure.
Time frame: OLE baseline (DBTP Week 96), OLE Week 52
Population: Full Analysis Set (FAS) included all participants who were randomized to study treatment. No summary analysis was done as study was prematurely terminated and participant wise data was reported. Here, number analyzed signifies specific participant evaluated in the arm of this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Teriflunomide | OLE Period: Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue (MS) 8a Score at Week 52 | Participant 1 | 43 T-score |
| Teriflunomide | OLE Period: Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue (MS) 8a Score at Week 52 | Participant 2 | 42 T-score |
| Teriflunomide | OLE Period: Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue (MS) 8a Score at Week 52 | Participant 3 | 41 T-score |
Secondary
OLE Period: Change From Baseline in PROMISnq Physical Function (PF) Multiple Sclerosis (MS) 15a at Week 52
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 ranges from 10 to 65. Higher T-scores represent higher physical function. Participant wise data was reported for this outcome measure.
Time frame: OLE Baseline (DBTP Week 96), OLE Week 52
Population: Full Analysis Set (FAS) included all participants who were randomized to study treatment. No summary analysis was done as study was prematurely terminated and participant wise data was reported. Here, number analyzed signifies specific participant evaluated in the arm of this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Teriflunomide | OLE Period: Change From Baseline in PROMISnq Physical Function (PF) Multiple Sclerosis (MS) 15a at Week 52 | Participant 1 | 52 T-score |
| Teriflunomide | OLE Period: Change From Baseline in PROMISnq Physical Function (PF) Multiple Sclerosis (MS) 15a at Week 52 | Participant 2 | 63 T-score |
| Teriflunomide | OLE Period: Change From Baseline in PROMISnq Physical Function (PF) Multiple Sclerosis (MS) 15a at Week 52 | Participant 3 | 51 T-score |
Secondary
OLE Period: Change From Baseline in T2 Lesion Volume
Change from baseline in T2 lesion volume was reported. Participant wise data was reported for this outcome measure.
Time frame: From OLE baseline (DBTP Week 96) to OLE Week 52
Population: Full Analysis Set (FAS) included all participants who were randomized to study treatment. No summary analysis was done as study was prematurely terminated and participant wise data was reported. Here, number analyzed signifies specific participant evaluated in the arm of this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Teriflunomide | OLE Period: Change From Baseline in T2 Lesion Volume | Participant 1 | 0.471 milliliter (mL) |
| Teriflunomide | OLE Period: Change From Baseline in T2 Lesion Volume | Participant 2 | -0.111 milliliter (mL) |
| Teriflunomide | OLE Period: Change From Baseline in T2 Lesion Volume | Participant 3 | 0 milliliter (mL) |
Secondary
OLE Period: Number of New or Enlarging T2 Lesions
Analysis of number of new or enlarging T2 lesions 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. Participant wise data was reported for this outcome measure.
Time frame: From OLE baseline (DBTP Week 96) to OLE Week 52
Population: Full Analysis Set (FAS) included all participants who were randomized to study treatment. No summary analysis was done as study was prematurely terminated and participant wise data was reported. Here, number analyzed signifies specific participant evaluated in the arm of this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Teriflunomide | OLE Period: Number of New or Enlarging T2 Lesions | Participant 1 | 11 number of lesions |
| Teriflunomide | OLE Period: Number of New or Enlarging T2 Lesions | Participant 2 | 0 number of lesions |
| Teriflunomide | OLE Period: Number of New or Enlarging T2 Lesions | Participant 3 | 0 number of lesions |
Secondary
OLE Period: Number of Participants With Abnormalities in Electrocardiograms (ECGs) Findings
ECG recordings included, heart rate, PR interval and QRS duration. ECG recordings were obtained after the participants have rested for at least 5 minutes in supine position. The number of participants with abnormalities in ECG findings were reported.
Time frame: From OLE baseline (DBTP Week 96) to OLE Week 52
Population: Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Teriflunomide | OLE Period: Number of Participants With Abnormalities in Electrocardiograms (ECGs) Findings | 1 Participants |
Secondary
OLE Period: Number of Participants With Abnormalities in Laboratory Parameters
Laboratory investigation included hematology, biochemistry and coagulation. The number of participants with abnormalities in laboratory parameters were reported.
Time frame: From OLE baseline (DBTP Week 96) to OLE Week 52
Population: Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Teriflunomide | OLE Period: Number of Participants With Abnormalities in Laboratory Parameters | Hematology | 1 Participants |
| Teriflunomide | OLE Period: Number of Participants With Abnormalities in Laboratory Parameters | Biochemistry | 1 Participants |
| Teriflunomide | OLE Period: Number of Participants With Abnormalities in Laboratory Parameters | Coagulation | 0 Participants |
Secondary
OLE Period: Number of Participants With Abnormalities in Vital Signs
Vital signs included temperature, pulse rate, respiration rate and blood pressure and weight (taken after 5 minutes in the sitting position). The number of participants with abnormalities in vital signs were reported.
Time frame: From OLE baseline (DBTP Week 96) to OLE Week 52
Population: Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Teriflunomide | OLE Period: Number of Participants With Abnormalities in Vital Signs | 0 Participants |
Secondary
OLE 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).
Time frame: From OLE baseline (DBTP Week 96) to OLE Week 52
Population: Full analysis Set (FAS) included all participants who were randomized to study treatment. No participants did not meet the baseline criteria of EDSS \>=2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Teriflunomide | OLE Period: Percentage of Participants With 24-Week Confirmed Disability Improvement (CDI) as Measured by Expanded Disability Status Scale (EDSS) | 0 percentage of participants |
Secondary
OLE 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).
Time frame: From OLE baseline (DBTP Week 96) to OLE Week 52
Population: Full Analysis Set (FAS) included all participants who were randomized to study treatment. No participants with confirmed disability progression sustained for 24 weeks as measured on EDSS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Teriflunomide | OLE Period: Percentage of Participants Without 24-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS) | 0 percentage of participants |
Secondary
OLE Period: Symbol Digit Modalities Test (SDMT)
The SDMT is a test of information 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 indicated improvement and lower scores indicated worsening. Participant wise data was reported for this outcome measure.
Time frame: Assessed from OLE baseline to OLE Week 96; OLE Week 48 were reported for Participants 1 and 2 and OLE Week 12 were reported for Participant 3
Population: Full Analysis Set (FAS) included all participants who were randomized to study treatment. No summary analysis was done as study was prematurely terminated and participant wise data was reported. Here, number analyzed signifies specific participant evaluated in the arm of this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Teriflunomide | OLE Period: Symbol Digit Modalities Test (SDMT) | Participant 1 | 60 units on a scale |
| Teriflunomide | OLE Period: Symbol Digit Modalities Test (SDMT) | Participant 2 | 40 units on a scale |
| Teriflunomide | OLE Period: Symbol Digit Modalities Test (SDMT) | Participant 3 | 50 units on a scale |