Relapsing-remitting Multiple Sclerosis
Conditions
Keywords
Evobrutinib, Avonex®, Interferon-beta 1a, Relapsing Multiple Sclerosis
Brief summary
The study was to evaluate the efficacy and safety of evobrutinib administered orally twice daily versus Interferon-beta-1a (Avonex®), once a week intramuscularly in participants with Relapsing Multiple Sclerosis (RMS).
Interventions
DRUGEvobrutinib
Participants received evobrutinib twice daily (BID).
DRUGAvonex®
Participants received avonex® IM injection once a week.
Participants received IM injection of placebo matched to avonex® once a week.
Participants received placebo matched to evobrutinib twice a day.
Sponsors
Merck KGaA, Darmstadt, Germany
EMD Serono Research & Development Institute, Inc.
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 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 EDSS score of 0 to 5.5 at Baseline. Participants with an EDSS score \<= 2 at screening 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. * Female participants must be neither pregnant nor breast-feeding and 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. * 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. * 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 |
|---|---|---|
| Annualized Relapse Rate (ARR) | At Week 96 | The annualized relapse rate at 96 weeks was to be calculated based on qualified relapses. A qualifying relapse is the occurrence of new or worsening neurological symptoms attributable to MS. The relapse should be accompanied by an increase of 0.5 points or more on Expanded Disability Status Scale (EDSS), or 2 points increase on one of the Functional System Scores (FSS), or 1 point increase on at least two of the FSS. The increase in FSS scores must be related to the neurological symptoms which were reported as new or worsening. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Occurrence of 24-Week Confirmed Expanded Disability Status Scale (EDSS) Progression | Baseline up to 96 weeks | EDSS is an ordinal scale in half-point increments that measures disability in participants with MS. EDSS progression is defined as an increase of 1 point or more from Baseline EDSS score when the Baseline score is 5.0 or less, and an increase of 0.5 points or more when the Baseline score is 5.5 or greater. Time to first occurrence of 24-week confirmed EDSS progression is defined as the time from randomization to the first EDSS progression event that was confirmed at a regularly scheduled visit at least 24 weeks later. |
| Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) Short Form Score at Week 96 | Baseline, Week 96 | The PROMIS PF Short Form is specific to measuring the physical function domain of MS patients, with each item on the form scored on a T-score metric. Higher scores indicate higher PF. Change from baseline at Week 96 is the difference between the PROMIS PF scores at 96 weeks and at baseline. |
| Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form Score at Week 96 | Baseline, Week 96 | The PROMIS Fatigue Short Form is specific to measuring the fatigue domain of MS patients, with each item on the form scored on a T-score metric. Higher scores indicate higher fatigue. Change from baseline at Week 96 is the difference between the PROMIS Fatigue scores at 96 weeks and at baseline. |
| Total Number of Gadolinium-Enhancing (Gd+) Time Constant 1 (T1) Lesions Assessed by Magnetic Resonance Imaging (MRI) Scans at Week 24, 48, and 96 | At Week 24, 48 and 96 | Total number of Gd+ T1 lesions was to be assessed using magnetic resonance imaging (MRI). |
| Total Number of New or Enlarging Time Constant 2 (T2) Lesions Assessed by Magnetic Resonance Imaging (MRI) Scans at Week 24, 48, and 96 | At Week 24, 48 and 96 | Total number of new or enlarging T2 lesions was to be assessed using magnetic resonance imaging (MRI). |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs) | Baseline up to 254 days | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal relationship with this treatment. Therefore, an AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, regardless if it is considered related to the medicinal product. TEAE is an AE that started after study drug treatment; or if the event was continuous from baseline & was serious, related to investigational medicinal product (IMP), or resulted in death, discontinuation, interruption or reduction of study therapy. TEAEs included both serious 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. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Baseline up to 254 days | Adverse event (AE) was defined as any untoward medical occurrence in a participant, which does not necessarily have causal relationship with treatment. A serious AE was defined as an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged in participant hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs included both serious TEAEs and non-serious TEAEs. Severity of TEAEs were graded using NCI CTCAE v4.03 toxicity grades, as follows: Grade 1= Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death. Number of participants with TEAEs based on severity were reported. |
| Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | At Day 1, Week 2 unscheduled 1, Week 12 and Early Discontinuation (ED) (up to approximately 36 weeks | DBP and SBP were measured in semi-supine position after 5 minutes rest for the participants at indicated time points. |
| Vital Signs: Pulse Rate | At Day 1, Week 2 unscheduled 1, Week 12 and Early Discontinuation ED (up to approximately 36 weeks) | Pulse rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. |
| Vital Signs: Respiratory Rate | At Day 1, Week 2 unscheduled 1, Week 12 and Early Discontinuation ED (up to approximately 36 weeks) | Respiration rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. |
| Vital Signs: Temperature | At Day 1, Week 2 unscheduled 1, Week 12 and Early Discontinuation (ED) (up to approximately 36 weeks) | Temperature was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. |
| Time to First Occurrence of 12-Week Confirmed Expanded Disability Status Scale (EDSS) Progression | Baseline up to 96 weeks | EDSS is an ordinal scale in half-point increments that measures disability in participants with MS. EDSS progression is defined as an increase of 1 point or more from Baseline EDSS score when the Baseline score is 5.0 or less, and an increase of 0.5 points or more when the Baseline score is 5.5 or greater. Time to first occurrence of 12-week confirmed EDSS progression is defined as the time from randomization to the first EDSS progression event that was confirmed at a regularly scheduled visit at least 12 weeks later. |
| Number of Participants With Abnormal Lab Values | Baseline up to 254 days | The total number of participants with laboratory test abnormalities was assessed. Clinical laboratory tests included hematology, coagulation, biochemistry and urinalysis. |
| Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | Baseline up to 254 days | ECG parameters included heart rhythm, heart rate, QRS intervals, QT intervals, RR intervals and corrected QT (QTc) intervals. |
| Absolute Concentrations of Immunoglobulin (Ig) A Level | At Day 1 and Day 92 | Absolute concentrations of Immunoglobulin (Ig) A was reported. |
| Absolute Concentrations of Immunoglobulin (Ig) G Level | At Day 1 and Day 92 | Absolute concentrations of Immunoglobulin (Ig) E was reported. |
| Absolute Concentrations of Immunoglobulin (Ig) M Level | At Day 1 and Day 92 | Absolute concentrations of Immunoglobulin (Ig) M was reported. |
| Absolute Concentrations of Immunoglobulin (Ig) E Level | At Day 1 and Day 92 | Absolute concentrations of Immunoglobulin (Ig) E was reported. |
| Change From Baseline in Immunoglobulin (Ig) A Level | At Day 1 and Day 92 | Change from baseline in immunoglobulin (Ig) A level was reported. |
| Change From Baseline in Immunoglobulin (Ig) E Level | At Day 1 and Day 92 | Change from baseline in immunoglobulin (Ig) E level was reported. |
| Change From Baseline in Immunoglobulin (Ig) G Level | At Day 1 and Day 92 | Change from baseline in immunoglobulin (Ig) G level was reported. |
| Change From Baseline in Immunoglobulin (Ig) M Level | At Day 1 and Day 92 | Change from baseline in immunoglobulin (Ig) M level was reported. |
| Vital Signs: Weight | At Day 1, Week 2 unscheduled 1, Week 12 and Early Discontinuation (up to approximately 36 weeks) | — |
Countries
Germany, United States
Participant flow
Pre-assignment details
This study was to be conducted in 2 periods; double blind period and open label extension period. However, due to early termination of the study, the sponsor decided not to conduct the open label extension period. A total of 950 participants were planned to be included in 1:1 to treatment with evobrutinib or Avonex, however only 1 participant was enrolled in evobrutinib due to early termination.
Participants by arm
| Arm | Count |
|---|---|
| Evobrutinib + Avonex® Matched Placebo Participants received active evobrutinib twice daily (BID) along with concomitant intramuscular (IM) injection of placebo matched to Avonex® once a week. Treatment period was planned to be of 96 weeks. | 1 |
| Avonex® + Evobrutinib Matched Placebo Participants received IM injection of active Avonex® once a week along with concomitant placebo matched to evobrutinib BID. Treatment period was planned to be of 96 weeks. | 0 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Study Termination | 1 | 0 |
Baseline characteristics
| Characteristic | Evobrutinib + Avonex® Matched Placebo | Avonex® + Evobrutinib Matched Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 0 |
| other Total, other adverse events | 1 / 1 | 0 / 0 |
| serious Total, serious adverse events | 0 / 1 | 0 / 0 |
Outcome results
Primary
Annualized Relapse Rate (ARR)
The annualized relapse rate at 96 weeks was to be calculated based on qualified relapses. A qualifying relapse is the occurrence of new or worsening neurological symptoms attributable to MS. The relapse should be accompanied by an increase of 0.5 points or more on Expanded Disability Status Scale (EDSS), or 2 points increase on one of the Functional System Scores (FSS), or 1 point increase on at least two of the FSS. The increase in FSS scores must be related to the neurological symptoms which were reported as new or worsening.
Time frame: At Week 96
Population: Following analysis of open label extension (OLE) data from RMS phase 2 study (MS200527- 0086), it was determined that a change in active comparator warranted in phase 3 RMS comprised of trial MS200527-0074. Consequently, this trial terminated early, therefore, it was decided as per Statistical Analysis Plan not to report the efficacy data for this study.
Secondary
Absolute Concentrations of Immunoglobulin (Ig) A Level
Absolute concentrations of Immunoglobulin (Ig) A was reported.
Time frame: At Day 1 and Day 92
Population: SAF analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Evobrutinib + Avonex® Matched Placebo | Absolute Concentrations of Immunoglobulin (Ig) A Level | Day 1 | 0.8 gram per liter (g/L) |
| Evobrutinib + Avonex® Matched Placebo | Absolute Concentrations of Immunoglobulin (Ig) A Level | Day 92 | 0.92 gram per liter (g/L) |
Secondary
Absolute Concentrations of Immunoglobulin (Ig) E Level
Absolute concentrations of Immunoglobulin (Ig) E was reported.
Time frame: At Day 1 and Day 92
Population: SAF analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Evobrutinib + Avonex® Matched Placebo | Absolute Concentrations of Immunoglobulin (Ig) E Level | Day 1 | 14.1 International units per milliliter |
| Evobrutinib + Avonex® Matched Placebo | Absolute Concentrations of Immunoglobulin (Ig) E Level | Day 92 | 16.7 International units per milliliter |
Secondary
Absolute Concentrations of Immunoglobulin (Ig) G Level
Absolute concentrations of Immunoglobulin (Ig) E was reported.
Time frame: At Day 1 and Day 92
Population: SAF analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Evobrutinib + Avonex® Matched Placebo | Absolute Concentrations of Immunoglobulin (Ig) G Level | Day 1 | 5.54 grams per liter (g/L) |
| Evobrutinib + Avonex® Matched Placebo | Absolute Concentrations of Immunoglobulin (Ig) G Level | Day 92 | 6.11 grams per liter (g/L) |
Secondary
Absolute Concentrations of Immunoglobulin (Ig) M Level
Absolute concentrations of Immunoglobulin (Ig) M was reported.
Time frame: At Day 1 and Day 92
Population: SAF analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Evobrutinib + Avonex® Matched Placebo | Absolute Concentrations of Immunoglobulin (Ig) M Level | Day 1 | 0.29 grams per liter (g/L) |
| Evobrutinib + Avonex® Matched Placebo | Absolute Concentrations of Immunoglobulin (Ig) M Level | Day 92 | 0.25 grams per liter (g/L) |
Secondary
Change From Baseline in Immunoglobulin (Ig) A Level
Change from baseline in immunoglobulin (Ig) A level was reported.
Time frame: At Day 1 and Day 92
Population: SAF analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Evobrutinib + Avonex® Matched Placebo | Change From Baseline in Immunoglobulin (Ig) A Level | 0.12 gram per liter (g/L) |
Secondary
Change From Baseline in Immunoglobulin (Ig) E Level
Change from baseline in immunoglobulin (Ig) E level was reported.
Time frame: At Day 1 and Day 92
Population: SAF analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Evobrutinib + Avonex® Matched Placebo | Change From Baseline in Immunoglobulin (Ig) E Level | 2.6 International units per milliliter |
Secondary
Change From Baseline in Immunoglobulin (Ig) G Level
Change from baseline in immunoglobulin (Ig) G level was reported.
Time frame: At Day 1 and Day 92
Population: SAF analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Evobrutinib + Avonex® Matched Placebo | Change From Baseline in Immunoglobulin (Ig) G Level | 0.57 grams per liter (g/L) |
Secondary
Change From Baseline in Immunoglobulin (Ig) M Level
Change from baseline in immunoglobulin (Ig) M level was reported.
Time frame: At Day 1 and Day 92
Population: SAF analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Evobrutinib + Avonex® Matched Placebo | Change From Baseline in Immunoglobulin (Ig) M Level | -0.04 grams per liter (g/L) |
Secondary
Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form Score at Week 96
The PROMIS Fatigue Short Form is specific to measuring the fatigue domain of MS patients, with each item on the form scored on a T-score metric. Higher scores indicate higher fatigue. Change from baseline at Week 96 is the difference between the PROMIS Fatigue scores at 96 weeks and at baseline.
Time frame: Baseline, Week 96
Population: Following analysis of open label extension (OLE) data from RMS phase 2 study (MS200527- 0086), it was determined that a change in active comparator warranted in phase 3 RMS comprised of trial MS200527-0074. Consequently, this trial terminated early, therefore, it was decided as per Statistical Analysis Plan not to report the efficacy data for this study.
Secondary
Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) Short Form Score at Week 96
The PROMIS PF Short Form is specific to measuring the physical function domain of MS patients, with each item on the form scored on a T-score metric. Higher scores indicate higher PF. Change from baseline at Week 96 is the difference between the PROMIS PF scores at 96 weeks and at baseline.
Time frame: Baseline, Week 96
Population: Following analysis of open label extension (OLE) data from RMS phase 2 study (MS200527- 0086), it was determined that a change in active comparator warranted in phase 3 RMS comprised of trial MS200527-0074. Consequently, this trial terminated early, therefore, it was decided as per Statistical Analysis Plan not to report the efficacy data for this study.
Secondary
Number of Participants With Abnormal Lab Values
The total number of participants with laboratory test abnormalities was assessed. Clinical laboratory tests included hematology, coagulation, biochemistry and urinalysis.
Time frame: Baseline up to 254 days
Population: SAF analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Evobrutinib + Avonex® Matched Placebo | Number of Participants With Abnormal Lab Values | 0 Participants |
Secondary
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
ECG parameters included heart rhythm, heart rate, QRS intervals, QT intervals, RR intervals and corrected QT (QTc) intervals.
Time frame: Baseline up to 254 days
Population: SAF analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Evobrutinib + Avonex® Matched Placebo | Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | 0 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)
Adverse event (AE) was defined as any untoward medical occurrence in a participant, which does not necessarily have causal relationship with treatment. A serious AE was defined as an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged in participant hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs included both serious TEAEs and non-serious TEAEs. Severity of TEAEs were graded using NCI CTCAE v4.03 toxicity grades, as follows: Grade 1= Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death. Number of participants with TEAEs based on severity were reported.
Time frame: Baseline up to 254 days
Population: Safety (SAF) analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Evobrutinib + Avonex® Matched Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade 1 | 1 Participants |
| Evobrutinib + Avonex® Matched Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade 2 | 0 Participants |
| Evobrutinib + Avonex® Matched Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade 3 | 0 Participants |
| Evobrutinib + Avonex® Matched Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade 4 | 0 Participants |
| Evobrutinib + Avonex® Matched Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade 5 | 0 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs)
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal relationship with this treatment. Therefore, an AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, regardless if it is considered related to the medicinal product. TEAE is an AE that started after study drug treatment; or if the event was continuous from baseline & was serious, related to investigational medicinal product (IMP), or resulted in death, discontinuation, interruption or reduction of study therapy. TEAEs included both serious 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: Baseline up to 254 days
Population: SAF analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Evobrutinib + Avonex® Matched Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs) | Participants with AESIs | 0 Participants |
| Evobrutinib + Avonex® Matched Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs) | Participants with TEAEs | 1 Participants |
| Evobrutinib + Avonex® Matched Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs) | Participants with Serious TEAEs | 0 Participants |
Secondary
Time to First Occurrence of 12-Week Confirmed Expanded Disability Status Scale (EDSS) Progression
EDSS is an ordinal scale in half-point increments that measures disability in participants with MS. EDSS progression is defined as an increase of 1 point or more from Baseline EDSS score when the Baseline score is 5.0 or less, and an increase of 0.5 points or more when the Baseline score is 5.5 or greater. Time to first occurrence of 12-week confirmed EDSS progression is defined as the time from randomization to the first EDSS progression event that was confirmed at a regularly scheduled visit at least 12 weeks later.
Time frame: Baseline up to 96 weeks
Population: Following analysis of open label extension (OLE) data from RMS phase 2 study (MS200527- 0086), it was determined that a change in active comparator warranted in phase 3 RMS comprised of trial MS200527-0074. Consequently, this trial terminated early, therefore, it was decided as per Statistical Analysis Plan not to report the efficacy data for this study.
Secondary
Time to First Occurrence of 24-Week Confirmed Expanded Disability Status Scale (EDSS) Progression
EDSS is an ordinal scale in half-point increments that measures disability in participants with MS. EDSS progression is defined as an increase of 1 point or more from Baseline EDSS score when the Baseline score is 5.0 or less, and an increase of 0.5 points or more when the Baseline score is 5.5 or greater. Time to first occurrence of 24-week confirmed EDSS progression is defined as the time from randomization to the first EDSS progression event that was confirmed at a regularly scheduled visit at least 24 weeks later.
Time frame: Baseline up to 96 weeks
Population: Following analysis of open label extension (OLE) data from RMS phase 2 study (MS200527- 0086), it was determined that a change in active comparator warranted in phase 3 RMS comprised of trial MS200527-0074. Consequently, this trial terminated early, therefore, it was decided as per Statistical Analysis Plan not to report the efficacy data for this study.
Secondary
Total Number of Gadolinium-Enhancing (Gd+) Time Constant 1 (T1) Lesions Assessed by Magnetic Resonance Imaging (MRI) Scans at Week 24, 48, and 96
Total number of Gd+ T1 lesions was to be assessed using magnetic resonance imaging (MRI).
Time frame: At Week 24, 48 and 96
Population: Following analysis of open label extension (OLE) data from RMS phase 2 study (MS200527- 0086), it was determined that a change in active comparator warranted in phase 3 RMS comprised of trial MS200527-0074. Consequently, this trial terminated early, therefore, it was decided as per Statistical Analysis Plan not to report the efficacy data for this study.
Secondary
Total Number of New or Enlarging Time Constant 2 (T2) Lesions Assessed by Magnetic Resonance Imaging (MRI) Scans at Week 24, 48, and 96
Total number of new or enlarging T2 lesions was to be assessed using magnetic resonance imaging (MRI).
Time frame: At Week 24, 48 and 96
Population: Following analysis of open label extension (OLE) data from RMS phase 2 study (MS200527- 0086), it was determined that a change in active comparator warranted in phase 3 RMS comprised of trial MS200527-0074. Consequently, this trial terminated early, therefore, it was decided as per Statistical Analysis Plan not to report the efficacy data for this study.
Secondary
Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
DBP and SBP were measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Time frame: At Day 1, Week 2 unscheduled 1, Week 12 and Early Discontinuation (ED) (up to approximately 36 weeks
Population: SAF analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Evobrutinib + Avonex® Matched Placebo | Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP: Day 1 | 72 Millimeters of mercury (mmHg) |
| Evobrutinib + Avonex® Matched Placebo | Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP: Week 2 unscheduled 1 | 68 Millimeters of mercury (mmHg) |
| Evobrutinib + Avonex® Matched Placebo | Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP: Week 12 | 76 Millimeters of mercury (mmHg) |
| Evobrutinib + Avonex® Matched Placebo | Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP: ED (up to approximately 36 weeks) | 84 Millimeters of mercury (mmHg) |
| Evobrutinib + Avonex® Matched Placebo | Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP: Day 1 | 124 Millimeters of mercury (mmHg) |
| Evobrutinib + Avonex® Matched Placebo | Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP: Week 2 unscheduled 1 | 119 Millimeters of mercury (mmHg) |
| Evobrutinib + Avonex® Matched Placebo | Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP: Week 12 | 130 Millimeters of mercury (mmHg) |
| Evobrutinib + Avonex® Matched Placebo | Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP:ED (up to approximately 36 weeks) | 140 Millimeters of mercury (mmHg) |
Secondary
Vital Signs: Pulse Rate
Pulse rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Time frame: At Day 1, Week 2 unscheduled 1, Week 12 and Early Discontinuation ED (up to approximately 36 weeks)
Population: SAF analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Evobrutinib + Avonex® Matched Placebo | Vital Signs: Pulse Rate | Pulse rate: ED (up to approximately 36 weeks) | 80 Beats per minute |
| Evobrutinib + Avonex® Matched Placebo | Vital Signs: Pulse Rate | Pulse rate: Day 1 | 71 Beats per minute |
| Evobrutinib + Avonex® Matched Placebo | Vital Signs: Pulse Rate | Pulse rate: Week 2 unscheduled 1 | 77 Beats per minute |
| Evobrutinib + Avonex® Matched Placebo | Vital Signs: Pulse Rate | Pulse rate: Week 12 | 75 Beats per minute |
Secondary
Vital Signs: Respiratory Rate
Respiration rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Time frame: At Day 1, Week 2 unscheduled 1, Week 12 and Early Discontinuation ED (up to approximately 36 weeks)
Population: SAF analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Evobrutinib + Avonex® Matched Placebo | Vital Signs: Respiratory Rate | Respiratory rate: Day 1 | 12 Breaths Per Minute |
| Evobrutinib + Avonex® Matched Placebo | Vital Signs: Respiratory Rate | Respiratory rate: Week 2 unscheduled 1 | 18 Breaths Per Minute |
| Evobrutinib + Avonex® Matched Placebo | Vital Signs: Respiratory Rate | Respiratory rate: Week 12 | 12 Breaths Per Minute |
| Evobrutinib + Avonex® Matched Placebo | Vital Signs: Respiratory Rate | Respiratory rate: ED (up to approximately 36 weeks) | 14 Breaths Per Minute |
Secondary
Vital Signs: Temperature
Temperature was measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Time frame: At Day 1, Week 2 unscheduled 1, Week 12 and Early Discontinuation (ED) (up to approximately 36 weeks)
Population: SAF analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Evobrutinib + Avonex® Matched Placebo | Vital Signs: Temperature | Day 1 | 36.4 Degree celsius |
| Evobrutinib + Avonex® Matched Placebo | Vital Signs: Temperature | Week 2 unscheduled 1 | 36.7 Degree celsius |
| Evobrutinib + Avonex® Matched Placebo | Vital Signs: Temperature | Week 12 | 36.9 Degree celsius |
| Evobrutinib + Avonex® Matched Placebo | Vital Signs: Temperature | ED (up to approximately 36 weeks) | 36.7 Degree celsius |
Secondary
Vital Signs: Weight
Time frame: At Day 1, Week 2 unscheduled 1, Week 12 and Early Discontinuation (up to approximately 36 weeks)
Population: SAF analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Evobrutinib + Avonex® Matched Placebo | Vital Signs: Weight | Day 1 | 91.4 kilogram (kg) |
| Evobrutinib + Avonex® Matched Placebo | Vital Signs: Weight | Week 2 unscheduled 1 | 92.3 kilogram (kg) |
| Evobrutinib + Avonex® Matched Placebo | Vital Signs: Weight | Week 12 | 92.6 kilogram (kg) |
| Evobrutinib + Avonex® Matched Placebo | Vital Signs: Weight | ED (up to approximately 36 weeks) | 95.5 kilogram (kg) |