Study of Evobrutinib in Participants With Relapsing Multiple Sclerosis (RMS)

• Sponsor: EMD Serono Research & Development Institute, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT04032158
• Collaborator: Merck KGaA, Darmstadt, Germany (Industry)
• Enrollment: 3
• Locations: 2
• Arms: 2
• Actual Duration (Months): 7.7
• Patients Per Site: 1.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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 RMS.

Condition or Disease	Intervention/Treatment	Phase
Relapsing-remitting Multiple Sclerosis	Drug: Evobrutinib; Drug: Avonex®; Drug: Avonex® matched Placebo; Drug: Evobrutinib matched Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase III, Multicenter, Randomized, Parallel Group, Double Blind, Double Dummy, Active Controlled Study of Evobrutinib Compared With an Interferon Beta 1a (Avonex®), in Participants With Relapsing Multiple Sclerosis to Evaluate Efficacy and Safety
• Actual Study Start Date: Aug 26, 2019
• Actual Primary Completion Date: Apr 16, 2020
• Actual Study Completion Date: Apr 16, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Evobrutinib; Participants received evobrutinib twice daily (BID).; Other Names: M2951 ; Drug: Avonex® matched Placebo; Participants received IM injection of placebo matched to Avonex® once a week.
Active Comparator: 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.	Drug: Avonex®; Participants received avonex® IM injection once a week.; Drug: Evobrutinib matched Placebo; Participants received placebo matched to evobrutinib twice a day.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) MS Fatigue 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.

5. 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).

6. 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).

7. Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs) [Baseline up to 235 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 and was serious, related to study drug, or resulted in death, discontinuation, interruption or reduction of study therapy. TEAEs includes 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.

8. 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 235 days]

   TEAE is an AE that started after study drug treatment; or if the event was continuous from baseline and was serious, related to investigational medicinal product (IMP), or resulted in death, discontinuation, interruption or reduction of study therapy. 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.

9. Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) [At Day 1, 83, 125 and 155]

   DBP and SBP were measured in semi-supine position after 5 minutes rest for the participants at indicated time points.

10. Vital Signs: Pulse Rate [At Day 1, 83, 125 and 155]

    Pulse rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points.

11. Vital Signs: Respiratory Rate [At Day 1, 83, 125 and 155]

    Respiration rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points.

12. Vital Signs: Temperature [At Day 1, 83, 125 and 155]

    Temperature was measured in semi-supine position after 5 minutes rest for the participants at indicated time points.

13. Vital Signs: Weight [At Day 1, 83, 125 and 155]

14. Number of Participants With Abnormal Lab Values [Baseline up to 235 days]

    The total number of participants with laboratory test abnormalities was assessed. Clinical laboratory tests included hematology, coagulation, biochemistry and urinalysis.

15. Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities [Baseline up to 235 days]

    ECG parameters included heart rhythm, heart rate, QRS intervals, QT intervals, RR intervals and corrected QT (QTc) intervals.

16. Absolute Concentrations of Immunoglobulin (Ig) A Level [At Day 1, 83, 125 and 155]

    Absolute concentrations of Immunoglobulin (Ig) A was reported.

17. Absolute Concentrations of Immunoglobulin (Ig) E Level [At Day 1, 83, 125 and 155]

    Absolute concentrations of Immunoglobulin (Ig) E was reported.

18. Absolute Concentrations of Immunoglobulin (Ig) G Level [At Day 1, 83, 125 and 155]

    Absolute concentrations of Immunoglobulin (Ig) G was reported.

19. Absolute Concentrations of Immunoglobulin (Ig) M Level [At Day 1, 83, 125 and 155]

    Absolute concentrations of Immunoglobulin (Ig) M was reported.

20. Change From Baseline in Immunoglobulin (Ig) A Level [At Day 1, 83, 125 and 155]

    Change from baseline in immunoglobulin (Ig) A level was reported.

21. Change From Baseline in Immunoglobulin (Ig) E Level [At Day 1, 83, 125 and 155]

    Change from baseline in immunoglobulin (Ig) E level was reported.

22. Change From Baseline in Immunoglobulin (Ig) G Level [At Day 1, 83, 125 and 155]

    Change from baseline in immunoglobulin (Ig) G level was reported.

23. Change From Baseline in Immunoglobulin (Ig) M Level [At Day 1, 83, 125 and 155]

    Change from baseline in immunoglobulin (Ig) M level was reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts 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 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 exclusion criteria could apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Please Contact U.S. Medical Information	Rockland	Massachusetts	United States	02370
2	Please Contact the Communication Center	Darmstadt		Germany	64293

Sponsors and Collaborators

• EMD Serono Research & Development Institute, Inc.
• Merck KGaA, Darmstadt, Germany

Investigators

• Study Director: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Study Documents (Full-Text)

• Study Protocol - Sep 5, 2019
• Statistical Analysis Plan - May 28, 2020

More Information

Additional Information:

• Trial Awareness and Transparency website
• US Medical Information website, Medical Resources

Publications

None provided.

• Responsible Party: EMD Serono Research & Development Institute, Inc.
• ClinicalTrials.gov Identifier: NCT04032158
• Other Study ID Numbers: MS200527_0073; 2018-004701-11
• First Posted: Jul 25, 2019
• Last Update Posted: Aug 5, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by EMD Serono Research & Development Institute, Inc.: Evobrutinib; Avonex®; Interferon-beta 1a; Relapsing Multiple Sclerosis
• Additional relevant MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis; Interferon beta-1a

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	Experimental: Evobrutinib + Avonex® Matched Placebo	Active Comparator: Avonex® + Evobrutinib Matched Placebo
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	2	1
COMPLETED	0	0
NOT COMPLETED	2	1

Baseline Characteristics

Arm/Group Title	Experimental: Evobrutinib + Avonex® Matched Placebo	Active Comparator: Avonex® + Evobrutinib Matched Placebo	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	2	1	3
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	2 100%	1 100%	3 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	1 50%	1 100%	2 66.7%
Male	1 50%	0 0%	1 33.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 100%	1 33.3%
White	2 100%	0 0%	2 66.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Annualized Relapse Rate (ARR)
Description	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

Outcome Measure Data

Analysis Population Description

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 MS200527-0073. Consequently, this trial terminated early, therefore, it was decided as per Statistical Analysis Plan not to report the efficacy data for this study.

Arm/Group Title	Experimental: Evobrutinib + Avonex® Matched Placebo	Active Comparator: Avonex® + Evobrutinib Matched Placebo
Arm/Group Description	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.	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.
Measure Participants	0	0

2. Secondary Outcome

Title	Time to First Occurrence of 12-Week Confirmed Expanded Disability Status Scale (EDSS) Progression
Description	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

Outcome Measure Data

Analysis Population Description

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 MS200527-0073. Consequently, this trial terminated early, therefore, it was decided as per Statistical Analysis Plan not to report the efficacy data for this study.

Arm/Group Title	Experimental: Evobrutinib + Avonex® Matched Placebo	Active Comparator: Avonex® + Evobrutinib Matched Placebo
Arm/Group Description	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.	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.
Measure Participants	0	0

3. Secondary Outcome

Title	Time to First Occurrence of 24-Week Confirmed Expanded Disability Status Scale (EDSS) Progression
Description	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

Outcome Measure Data

Analysis Population Description

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 MS200527-0073. Consequently, this trial terminated early, therefore, it was decided as per Statistical Analysis Plan not to report the efficacy data for this study.

Arm/Group Title	Experimental: Evobrutinib + Avonex® Matched Placebo	Active Comparator: Avonex® + Evobrutinib Matched Placebo
Arm/Group Description	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.	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.
Measure Participants	0	0

4. Secondary Outcome

Title	Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) Short Form Score at Week 96
Description	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

Outcome Measure Data

Analysis Population Description

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 MS200527-0073. Consequently, this trial terminated early, therefore, it was decided as per Statistical Analysis Plan not to report the efficacy data for this study.

Arm/Group Title	Experimental: Evobrutinib + Avonex® Matched Placebo	Active Comparator: Avonex® + Evobrutinib Matched Placebo
Arm/Group Description	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.	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.
Measure Participants	0	0

5. Secondary Outcome

Title	Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) MS Fatigue Score at Week 96
Description	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

Outcome Measure Data

Analysis Population Description

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 MS200527-0073. Consequently, this trial terminated early, therefore, it was decided as per Statistical Analysis Plan not to report the efficacy data for this study.

Arm/Group Title	Experimental: Evobrutinib + Avonex® Matched Placebo	Active Comparator: Avonex® + Evobrutinib Matched Placebo
Arm/Group Description	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.	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.
Measure Participants	0	0

6. Secondary Outcome

Title	Total Number of Gadolinium-Enhancing (Gd+) Time Constant 1 (T1) Lesions Assessed by Magnetic Resonance Imaging (MRI) Scans at Week 24, 48, and 96
Description	Total number of Gd+ T1 lesions was to be assessed using magnetic resonance imaging (MRI).
Time Frame	At Week 24, 48 and 96

Outcome Measure Data

Analysis Population Description

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 MS200527-0073. Consequently, this trial terminated early, therefore, it was decided as per Statistical Analysis Plan not to report the efficacy data for this study.

Arm/Group Title	Experimental: Evobrutinib + Avonex® Matched Placebo	Active Comparator: Avonex® + Evobrutinib Matched Placebo
Arm/Group Description	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.	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.
Measure Participants	0	0

7. Secondary Outcome

Title	Total Number of New or Enlarging Time Constant 2 (T2) Lesions Assessed by Magnetic Resonance Imaging (MRI) Scans at Week 24, 48, and 96
Description	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

Outcome Measure Data

Analysis Population Description

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 MS200527-0073. Consequently, this trial terminated early, therefore, it was decided as per Statistical Analysis Plan not to report the efficacy data for this study.

Arm/Group Title	Experimental: Evobrutinib + Avonex® Matched Placebo	Active Comparator: Avonex® + Evobrutinib Matched Placebo
Arm/Group Description	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.	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.
Measure Participants	0	0

8. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs)
Description	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 and was serious, related to study drug, or resulted in death, discontinuation, interruption or reduction of study therapy. TEAEs includes 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	Baseline up to 235 days

Outcome Measure Data

Analysis Population Description

Safety (SAF) analysis set included all participants who were administered any dose of any study intervention.

Arm/Group Title	Experimental: Evobrutinib + Avonex® Matched Placebo	Active Comparator: Avonex® + Evobrutinib Matched Placebo
Arm/Group Description	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.	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.
Measure Participants	2	1
Participants with AESIs	0 0%	0 0%
Participants with TEAEs	2 100%	1 100%
Participants with Serious TEAEs	0 0%	0 0%

9. Secondary Outcome

Title	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)
Description	TEAE is an AE that started after study drug treatment; or if the event was continuous from baseline and was serious, related to investigational medicinal product (IMP), or resulted in death, discontinuation, interruption or reduction of study therapy. 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 235 days

Outcome Measure Data

Analysis Population Description

SAF analysis set included all participants who were administered any dose of any study intervention

Arm/Group Title	Experimental: Evobrutinib + Avonex® Matched Placebo	Active Comparator: Avonex® + Evobrutinib Matched Placebo
Arm/Group Description	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.	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.
Measure Participants	2	1
Grade 1	2 100%	0 0%
Grade 2	0 0%	1 100%
Grade 3	0 0%	0 0%
Grade 4	0 0%	0 0%
Grade 5	0 0%	0 0%

10. Secondary Outcome

Title	Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Description	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, 83, 125 and 155

Outcome Measure Data

Analysis Population Description

SAF analysis set included all participants who were administered any dose of any study intervention. No summary analysis was done. Following analysis of 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 MS200527-0073. Consequently, this trial terminated early. Therefore, participant wise data reported and number analyzed= specific participant evaluated in respective arm at specified timepoint.

Arm/Group Title	Experimental: Evobrutinib + Avonex® Matched Placebo	Active Comparator: Avonex® + Evobrutinib Matched Placebo
Arm/Group Description	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.	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.
Measure Participants	2	1
Participants 1 - DBP: Day 1	82
Participants 1 - DBP: Day 83	87
Participants 1 - DBP: Day 125	80
Participants 1 - DBP: Day 155	75
Participants 1 - SBP: Day 1	112
Participants 1 - SBP: Day 83	120
Participants 1 - SBP: Day 125	118
Participants 1 - SBP: Day 155	109
Participants 2 - DBP: Day 1	84
Participants 2 - DBP: Day 83	77
Participants 2 - DBP: Day 125	84
Participants 2 - DBP: Day 155	90
Participants 2 - SBP: Day 1	124
Participants 2 - SBP: Day 83	133
Participants 2 - SBP: Day 125	138
Participants 2 - SBP: Day 155	137
Participant 3 - DBP: Day 1	65
Participants 3 - DBP: Day 125	76
Participants 3 - SBP: Day 1	101
Participant 3 - SBP: Day 125	117

11. Secondary Outcome

Title	Vital Signs: Pulse Rate
Description	Pulse rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Time Frame	At Day 1, 83, 125 and 155

Outcome Measure Data

Analysis Population Description

SAF analysis set included all participants who were administered any dose of any study intervention. No summary analysis was done. Following analysis of 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 MS200527-0073. Consequently, this trial terminated early. Therefore, participant wise data reported and number analyzed= specific participant evaluated in respective arm at specified timepoint.

Arm/Group Title	Experimental: Evobrutinib + Avonex® Matched Placebo	Active Comparator: Avonex® + Evobrutinib Matched Placebo
Arm/Group Description	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.	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.
Measure Participants	2	1
Participants 1 - Pulse rate: Day 1	71
Participants 1 - Pulse rate: Day 83	69
Participants 1 - Pulse rate: Day 125	72
Participants 1 - Pulse rate: Day 155	75
Participants 2 - Pulse rate: Day 1	71
Participants 2 - Pulse rate: Day 83	66
Participants 2 - Pulse rate: Day 125	82
Participants 2 - Pulse rate: Day 155	82
Participant 3 - Pulse rate: Day 1	76
Participants 3 - Pulse rate: Day 125	75

12. Secondary Outcome

Title	Vital Signs: Respiratory Rate
Description	Respiration rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Time Frame	At Day 1, 83, 125 and 155

Outcome Measure Data

Analysis Population Description

SAF analysis set included all participants who were administered any dose of any study intervention. No summary analysis was done. Following analysis of 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 MS200527-0073. Consequently, this trial terminated early. Therefore, participant wise data reported and number analyzed= specific participant evaluated in respective arm at specified timepoint.

Arm/Group Title	Experimental: Evobrutinib + Avonex® Matched Placebo	Active Comparator: Avonex® + Evobrutinib Matched Placebo
Arm/Group Description	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.	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.
Measure Participants	2	1
Participants 1 - Respiratory rate: Day 1	20
Participants 1 - Respiratory rate: Day 83	18
Participants 1 - Respiratory rate: Day 125	18
Participants 1 - Respiratory rate: Day 155	20
Participants 2 - Respiratory rate: Day 1	18
Participants 2 - Respiratory rate: Day 83	20
Participants 2 - Respiratory rate: Day 125	18
Participants 2 - Respiratory rate: Day 155	20
Participant 3 - Respiratory rate: Day 1	18
Participants 3 - Respiratory rate: Day 125	18

13. Secondary Outcome

Title	Vital Signs: Temperature
Description	Temperature was measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Time Frame	At Day 1, 83, 125 and 155

Outcome Measure Data

Analysis Population Description

SAF analysis set included all participants who were administered any dose of any study intervention. No summary analysis was done. Following analysis of 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 MS200527-0073. Consequently, this trial terminated early. Therefore, participant wise data reported and number analyzed= specific participant evaluated in respective arm at specified timepoint.

Arm/Group Title	Experimental: Evobrutinib + Avonex® Matched Placebo	Active Comparator: Avonex® + Evobrutinib Matched Placebo
Arm/Group Description	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.	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.
Measure Participants	2	1
Participants 1: Day 1	35.7
Participants 1: Day 83	36.4
Participants 1: Day 125	36.9
Participants 1: Day 155	36.4
Participants 2: Day 1	36.9
Participants 2: Day 83	36.7
Participants 2: Day 125	36.9
Participants 2: Day 155	36.8
Participant 3: Day 1	36.5
Participants 3: Day 125	37.0

14. Secondary Outcome

Title	Vital Signs: Weight
Time Frame	At Day 1, 83, 125 and 155

Outcome Measure Data

Analysis Population Description

SAF analysis set included all participants who were administered any dose of any study intervention. No summary analysis was done. Following analysis of 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 MS200527-0073. Consequently, this trial terminated early. Therefore, participant wise data reported and number analyzed= specific participant evaluated in respective arm at specified timepoint.

Arm/Group Title	Experimental: Evobrutinib + Avonex® Matched Placebo	Active Comparator: Avonex® + Evobrutinib Matched Placebo
Arm/Group Description	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.	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.
Measure Participants	2	1
Participants 1: Day 1	75.7
Participants 1: Day 83	74.9
Participants 1: Day 125	77.3
Participants 1: Day 155	77.2
Participants 2: Day 1	89.0
Participants 2: Day 83	89.0
Participants 2: Day 125	92.2
Participants 2: Day 155	92.1
Participant 3: Day 1	40.8
Participants 3: Day 125	40.3

15. Secondary Outcome

Title	Number of Participants With Abnormal Lab Values
Description	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 235 days

Outcome Measure Data

Analysis Population Description

SAF analysis set included all participants who were administered any dose of any study intervention.

Arm/Group Title	Experimental: Evobrutinib + Avonex® Matched Placebo	Active Comparator: Avonex® + Evobrutinib Matched Placebo
Arm/Group Description	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.	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.
Measure Participants	2	1
Count of Participants [Participants]	0 0%	0 0%

16. Secondary Outcome

Title	Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
Description	ECG parameters included heart rhythm, heart rate, QRS intervals, QT intervals, RR intervals and corrected QT (QTc) intervals.
Time Frame	Baseline up to 235 days

Outcome Measure Data

Analysis Population Description

SAF analysis set included all participants who were administered any dose of any study intervention.

Arm/Group Title	Experimental: Evobrutinib + Avonex® Matched Placebo	Active Comparator: Avonex® + Evobrutinib Matched Placebo
Arm/Group Description	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.	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.
Measure Participants	2	1
Count of Participants [Participants]	0 0%	0 0%

17. Secondary Outcome

Title	Absolute Concentrations of Immunoglobulin (Ig) A Level
Description	Absolute concentrations of Immunoglobulin (Ig) A was reported.
Time Frame	At Day 1, 83, 125 and 155

Outcome Measure Data

Analysis Population Description

SAF analysis set included all participants who were administered any dose of any study intervention. No summary analysis was done. Following analysis of 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 MS200527-0073. Consequently, this trial terminated early. Therefore, participant wise data reported and number analyzed= specific participant evaluated in respective arm at specified timepoint.

Arm/Group Title	Experimental: Evobrutinib + Avonex® Matched Placebo	Active Comparator: Avonex® + Evobrutinib Matched Placebo
Arm/Group Description	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.	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.
Measure Participants	2	1
Participant 1: Day 1	2.09
Participant 1: Day 83	2.64
Participant 1: Day 125	2.64
Participant 1: Day 155	2.78
Participant 2: Day 1	1.64
Participant 2: Day 83	1.85
Participant 2: Day 125	2.2
Participant 2: Day 155	2.15
Participant 3: Day 1	2.09
Participant 3: Day 125	1.84

18. Secondary Outcome

Title	Absolute Concentrations of Immunoglobulin (Ig) E Level
Description	Absolute concentrations of Immunoglobulin (Ig) E was reported.
Time Frame	At Day 1, 83, 125 and 155

Outcome Measure Data

Analysis Population Description

SAF analysis set included all participants who were administered any dose of any study intervention. No summary analysis was done. Following analysis of 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 MS200527-0073. Consequently, this trial terminated early. Therefore, participant wise data reported and number analyzed= specific participant evaluated in respective arm at specified timepoint.

Arm/Group Title	Experimental: Evobrutinib + Avonex® Matched Placebo	Active Comparator: Avonex® + Evobrutinib Matched Placebo
Arm/Group Description	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.	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.
Measure Participants	2	1
Participant 1: Day 1	61
Participant 1: Day 83	108
Participant 1: Day 125	55.2
Participant 1: Day 155	71.9
Participant 2: Day 1	10.7
Participant 2: Day 83	12.3
Participant 2: Day 125	14.9
Participant 2: Day 155	11.4
Participant 3: Day 1	27.6
Participant 3: Day 125	23.5

19. Secondary Outcome

Title	Absolute Concentrations of Immunoglobulin (Ig) G Level
Description	Absolute concentrations of Immunoglobulin (Ig) G was reported.
Time Frame	At Day 1, 83, 125 and 155

Outcome Measure Data

Analysis Population Description

SAF analysis set included all participants who were administered any dose of any study intervention. No summary analysis was done. Following analysis of 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 MS200527-0073. Consequently, this trial terminated early. Therefore, participant wise data reported and number analyzed= specific participant evaluated in respective arm at specified timepoint.

Arm/Group Title	Experimental: Evobrutinib + Avonex® Matched Placebo	Active Comparator: Avonex® + Evobrutinib Matched Placebo
Arm/Group Description	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.	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.
Measure Participants	2	1
Participant 1: Day 1	16.49
Participant 1: Day 83	21.77
Participant 1: Day 125	19.34
Participant 1: Day 155	19.62
Participant 2: Day 1	9.46
Participant 2: Day 83	10.26
Participant 2: Day 125	11.23
Participant 2: Day 155	11.18
Participant 3: Day 1	12.52
Participant 3: Day 125	11.41

20. Secondary Outcome

Title	Absolute Concentrations of Immunoglobulin (Ig) M Level
Description	Absolute concentrations of Immunoglobulin (Ig) M was reported.
Time Frame	At Day 1, 83, 125 and 155

Outcome Measure Data

Analysis Population Description

SAF analysis set included all participants who were administered any dose of any study intervention. No summary analysis was done. Following analysis of 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 MS200527-0073. Consequently, this trial terminated early. Therefore, participant wise data reported and number analyzed= specific participant evaluated in respective arm at specified timepoint.

Arm/Group Title	Experimental: Evobrutinib + Avonex® Matched Placebo	Active Comparator: Avonex® + Evobrutinib Matched Placebo
Arm/Group Description	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.	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.
Measure Participants	2	1
Participant 1: Day 1	0.97
Participant 1: Day 83	1.47
Participant 1: Day 125	1.35
Participant 1: Day 155	1.43
Participant 2: Day 1	1.08
Participant 2: Day 83	0.84
Participant 2: Day 125	0.78
Participant 2: Day 155	1
Participant 3: Day 1	2.22
Participant 3: 125	1.91

21. Secondary Outcome

Title	Change From Baseline in Immunoglobulin (Ig) A Level
Description	Change from baseline in immunoglobulin (Ig) A level was reported.
Time Frame	At Day 1, 83, 125 and 155

Outcome Measure Data

Analysis Population Description

SAF analysis set included all participants who were administered any dose of any study intervention. No summary analysis was done. Following analysis of 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 MS200527-0073. Consequently, this trial terminated early. Therefore, participant wise data reported and number analyzed= specific participant evaluated in respective arm at specified timepoint.

Arm/Group Title	Experimental: Evobrutinib + Avonex® Matched Placebo	Active Comparator: Avonex® + Evobrutinib Matched Placebo
Arm/Group Description	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.	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.
Measure Participants	2	1
Participant 1: Day 83	0.55
Participant 1: Day 125	0.55
Participant 1: Day 155	0.69
Participant 2: Day 83	0.21
Participant 2: Day 125	0.56
Participant 2: Day 155	0.51
Participant 3: Day 125	-0.25

22. Secondary Outcome

Title	Change From Baseline in Immunoglobulin (Ig) E Level
Description	Change from baseline in immunoglobulin (Ig) E level was reported.
Time Frame	At Day 1, 83, 125 and 155

Outcome Measure Data

Analysis Population Description

SAF analysis set included all participants who were administered any dose of any study intervention. No summary analysis was done. Following analysis of 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 MS200527-0073. Consequently, this trial terminated early. Therefore, participant wise data reported and number analyzed= specific participant evaluated in respective arm at specified timepoint.

Arm/Group Title	Experimental: Evobrutinib + Avonex® Matched Placebo	Active Comparator: Avonex® + Evobrutinib Matched Placebo
Arm/Group Description	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.	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.
Measure Participants	2	1
Participant 1: Day 83	47
Participant 1: Day 125	-5.8
Participant 1: Day 155	10.9
Participant 2: Day 83	1.6
Participant 2: Day 125	4.2
Participant 2: Day 155	0.7
Participant 3: Day 125	-4.1

23. Secondary Outcome

Title	Change From Baseline in Immunoglobulin (Ig) G Level
Description	Change from baseline in immunoglobulin (Ig) G level was reported.
Time Frame	At Day 1, 83, 125 and 155

Outcome Measure Data

Analysis Population Description

SAF analysis set included all participants who were administered any dose of any study intervention. No summary analysis was done. Following analysis of 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 MS200527-0073. Consequently, this trial terminated early. Therefore, participant wise data reported and number analyzed= specific participant evaluated in respective arm at specified timepoint.

Arm/Group Title	Experimental: Evobrutinib + Avonex® Matched Placebo	Active Comparator: Avonex® + Evobrutinib Matched Placebo
Arm/Group Description	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.	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.
Measure Participants	2	1
Participant 1: Day 83	5.28
Participant 1: Day 125	2.85
Participant 1: Day 155	3.13
Participant 2: Day 83	0.8
Participant 2: Day 125	1.77
Participant 2: Day 155	1.72
Participant 3: Day 125	-1.11

24. Secondary Outcome

Title	Change From Baseline in Immunoglobulin (Ig) M Level
Description	Change from baseline in immunoglobulin (Ig) M level was reported.
Time Frame	At Day 1, 83, 125 and 155

Outcome Measure Data

Analysis Population Description

SAF analysis set included all participants who were administered any dose of any study intervention. No summary analysis was done. Following analysis of 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 MS200527-0073. Consequently, this trial terminated early. Therefore, participant wise data reported and number analyzed= specific participant evaluated in respective arm at specified timepoint.

Arm/Group Title	Experimental: Evobrutinib + Avonex® Matched Placebo	Active Comparator: Avonex® + Evobrutinib Matched Placebo
Arm/Group Description	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.	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.
Measure Participants	2	1
Participant 1: Day 83	0.5
Participant 1: Day 125	0.38
Participant 1: Day 155	0.46
Participant 2: Day 83	-0.24
Participant 2: Day 125	-0.3
Participant 2: Day 155	-0.08
Participant 3: Day 125	-0.31

Adverse Events

Time Frame	Baseline up to 235 days
Adverse Event Reporting Description	SAF analysis set included all participants who were administered any dose of any study intervention.
Arm/Group Title	Experimental: Evobrutinib + Avonex® Matched Placebo		Active Comparator: Avonex® + Evobrutinib Matched Placebo
Arm/Group Description	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.		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.
All Cause Mortality
	Experimental: Evobrutinib + Avonex® Matched Placebo		Active Comparator: Avonex® + Evobrutinib Matched Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/1 (0%)
Serious Adverse Events
	Experimental: Evobrutinib + Avonex® Matched Placebo		Active Comparator: Avonex® + Evobrutinib Matched Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Experimental: Evobrutinib + Avonex® Matched Placebo		Active Comparator: Avonex® + Evobrutinib Matched Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/2 (100%)		1/1 (100%)
Gastrointestinal disorders
Abdominal pain	0/2 (0%)		1/1 (100%)
Vomiting	0/2 (0%)		1/1 (100%)
General disorders
Drug eruption	1/2 (50%)		0/1 (0%)
Influenza like illness	1/2 (50%)		0/1 (0%)
Investigations
Neutrophil count decreased	0/2 (0%)		1/1 (100%)
Musculoskeletal and connective tissue disorders
Pain in jaw	1/2 (50%)		0/1 (0%)
Nervous system disorders
Tension headache	0/2 (0%)		1/1 (100%)
Paraesthesia	1/2 (50%)		0/1 (0%)
Skin and subcutaneous tissue disorders
Tinea cruris	1/2 (50%)		0/1 (0%)
Petechiae	1/2 (50%)		0/1 (0%)

Limitations/Caveats

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 MS200527-0073. Consequently, this trial terminated early, therefore, it was decided as per Statistical Analysis Plan not to report the efficacy data for this study.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.