Trial Outcomes & Findings for Study of Evobrutinib in Participants With Relapsing Multiple Sclerosis (RMS) (NCT NCT04032158)

NCT ID: NCT04032158

Last Updated: 2021-08-05

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

3 participants

Primary outcome timeframe

At Week 96

Results posted on

2021-08-05

Participant Flow

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.

Participant milestones

Participant milestones
Measure
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.
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.
Overall Study
STARTED
2
1
Overall Study
COMPLETED
0
0
Overall Study
NOT COMPLETED
2
1

Reasons for withdrawal

Reasons for withdrawal
Measure
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.
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.
Overall Study
Study Termination
2
1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Experimental: Evobrutinib + Avonex® Matched Placebo
n=2 Participants
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.
Active Comparator: Avonex® + Evobrutinib Matched Placebo
n=1 Participants
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
n=3 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
2 Participants
n=5 Participants
1 Participants
n=7 Participants
3 Participants
n=5 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Sex: Female, Male
Female
1 Participants
n=5 Participants
1 Participants
n=7 Participants
2 Participants
n=5 Participants
Sex: Female, Male
Male
1 Participants
n=5 Participants
0 Participants
n=7 Participants
1 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants
Race (NIH/OMB)
White
2 Participants
n=5 Participants
0 Participants
n=7 Participants
2 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants

PRIMARY outcome

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

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

Total number of Gd+ T1 lesions was to be assessed using magnetic resonance imaging (MRI).

Outcome measures

Outcome data not reported

SECONDARY outcome

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

Total number of new or enlarging T2 lesions was to be assessed using magnetic resonance imaging (MRI).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to 235 days

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

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.

Outcome measures

Outcome measures
Measure
Experimental: Evobrutinib + Avonex® Matched Placebo
n=2 Participants
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.
Active Comparator: Avonex® + Evobrutinib Matched Placebo
n=1 Participants
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.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs)
Participants with AESIs
0 Participants
0 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs)
Participants with TEAEs
2 Participants
1 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs)
Participants with Serious TEAEs
0 Participants
0 Participants

SECONDARY outcome

Timeframe: Baseline up to 235 days

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

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.

Outcome measures

Outcome measures
Measure
Experimental: Evobrutinib + Avonex® Matched Placebo
n=2 Participants
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.
Active Comparator: Avonex® + Evobrutinib Matched Placebo
n=1 Participants
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.
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
2 Participants
0 Participants
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
0 Participants
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
1 Participants
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
0 Participants
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
0 Participants

SECONDARY outcome

Timeframe: At Day 1, 83, 125 and 155

Population: 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.

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

Outcome measures

Outcome measures
Measure
Experimental: Evobrutinib + Avonex® Matched Placebo
n=2 Participants
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.
Active Comparator: Avonex® + Evobrutinib Matched Placebo
n=1 Participants
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.
Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Participants 1 - DBP: Day 1
82 Millimeters of mercury (mmHg)
Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Participants 1 - DBP: Day 83
87 Millimeters of mercury (mmHg)
Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Participants 1 - DBP: Day 125
80 Millimeters of mercury (mmHg)
Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Participants 1 - DBP: Day 155
75 Millimeters of mercury (mmHg)
Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Participants 1 - SBP: Day 1
112 Millimeters of mercury (mmHg)
Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Participants 1 - SBP: Day 83
120 Millimeters of mercury (mmHg)
Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Participants 1 - SBP: Day 125
118 Millimeters of mercury (mmHg)
Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Participants 1 - SBP: Day 155
109 Millimeters of mercury (mmHg)
Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Participants 2 - DBP: Day 1
84 Millimeters of mercury (mmHg)
Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Participants 2 - DBP: Day 83
77 Millimeters of mercury (mmHg)
Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Participants 2 - DBP: Day 125
84 Millimeters of mercury (mmHg)
Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Participants 2 - DBP: Day 155
90 Millimeters of mercury (mmHg)
Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Participants 2 - SBP: Day 1
124 Millimeters of mercury (mmHg)
Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Participants 2 - SBP: Day 83
133 Millimeters of mercury (mmHg)
Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Participants 2 - SBP: Day 125
138 Millimeters of mercury (mmHg)
Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Participants 2 - SBP: Day 155
137 Millimeters of mercury (mmHg)
Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Participant 3 - DBP: Day 1
65 Millimeters of mercury (mmHg)
Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Participants 3 - DBP: Day 125
76 Millimeters of mercury (mmHg)
Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Participants 3 - SBP: Day 1
101 Millimeters of mercury (mmHg)
Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Participant 3 - SBP: Day 125
117 Millimeters of mercury (mmHg)

SECONDARY outcome

Timeframe: At Day 1, 83, 125 and 155

Population: 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.

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

Outcome measures

Outcome measures
Measure
Experimental: Evobrutinib + Avonex® Matched Placebo
n=2 Participants
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.
Active Comparator: Avonex® + Evobrutinib Matched Placebo
n=1 Participants
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.
Vital Signs: Pulse Rate
Participants 1 - Pulse rate: Day 83
69 Beats per minute
Vital Signs: Pulse Rate
Participants 1 - Pulse rate: Day 125
72 Beats per minute
Vital Signs: Pulse Rate
Participants 1 - Pulse rate: Day 1
71 Beats per minute
Vital Signs: Pulse Rate
Participants 1 - Pulse rate: Day 155
75 Beats per minute
Vital Signs: Pulse Rate
Participants 2 - Pulse rate: Day 1
71 Beats per minute
Vital Signs: Pulse Rate
Participants 2 - Pulse rate: Day 83
66 Beats per minute
Vital Signs: Pulse Rate
Participants 2 - Pulse rate: Day 125
82 Beats per minute
Vital Signs: Pulse Rate
Participants 2 - Pulse rate: Day 155
82 Beats per minute
Vital Signs: Pulse Rate
Participant 3 - Pulse rate: Day 1
76 Beats per minute
Vital Signs: Pulse Rate
Participants 3 - Pulse rate: Day 125
75 Beats per minute

SECONDARY outcome

Timeframe: At Day 1, 83, 125 and 155

Population: 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.

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

Outcome measures

Outcome measures
Measure
Experimental: Evobrutinib + Avonex® Matched Placebo
n=2 Participants
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.
Active Comparator: Avonex® + Evobrutinib Matched Placebo
n=1 Participants
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.
Vital Signs: Respiratory Rate
Participants 3 - Respiratory rate: Day 125
18 Breaths Per Minute
Vital Signs: Respiratory Rate
Participants 1 - Respiratory rate: Day 1
20 Breaths Per Minute
Vital Signs: Respiratory Rate
Participants 1 - Respiratory rate: Day 83
18 Breaths Per Minute
Vital Signs: Respiratory Rate
Participants 1 - Respiratory rate: Day 125
18 Breaths Per Minute
Vital Signs: Respiratory Rate
Participants 1 - Respiratory rate: Day 155
20 Breaths Per Minute
Vital Signs: Respiratory Rate
Participants 2 - Respiratory rate: Day 1
18 Breaths Per Minute
Vital Signs: Respiratory Rate
Participants 2 - Respiratory rate: Day 83
20 Breaths Per Minute
Vital Signs: Respiratory Rate
Participants 2 - Respiratory rate: Day 125
18 Breaths Per Minute
Vital Signs: Respiratory Rate
Participants 2 - Respiratory rate: Day 155
20 Breaths Per Minute
Vital Signs: Respiratory Rate
Participant 3 - Respiratory rate: Day 1
18 Breaths Per Minute

SECONDARY outcome

Timeframe: At Day 1, 83, 125 and 155

Population: 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.

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

Outcome measures

Outcome measures
Measure
Experimental: Evobrutinib + Avonex® Matched Placebo
n=2 Participants
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.
Active Comparator: Avonex® + Evobrutinib Matched Placebo
n=1 Participants
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.
Vital Signs: Temperature
Participants 1: Day 1
35.7 Degree celsius
Vital Signs: Temperature
Participants 1: Day 83
36.4 Degree celsius
Vital Signs: Temperature
Participants 1: Day 125
36.9 Degree celsius
Vital Signs: Temperature
Participants 1: Day 155
36.4 Degree celsius
Vital Signs: Temperature
Participants 2: Day 1
36.9 Degree celsius
Vital Signs: Temperature
Participants 2: Day 83
36.7 Degree celsius
Vital Signs: Temperature
Participants 2: Day 125
36.9 Degree celsius
Vital Signs: Temperature
Participants 2: Day 155
36.8 Degree celsius
Vital Signs: Temperature
Participant 3: Day 1
36.5 Degree celsius
Vital Signs: Temperature
Participants 3: Day 125
37.0 Degree celsius

SECONDARY outcome

Timeframe: At Day 1, 83, 125 and 155

Population: 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.

Outcome measures

Outcome measures
Measure
Experimental: Evobrutinib + Avonex® Matched Placebo
n=2 Participants
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.
Active Comparator: Avonex® + Evobrutinib Matched Placebo
n=1 Participants
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.
Vital Signs: Weight
Participants 1: Day 1
75.7 kilogram (kg)
Vital Signs: Weight
Participants 1: Day 83
74.9 kilogram (kg)
Vital Signs: Weight
Participants 1: Day 125
77.3 kilogram (kg)
Vital Signs: Weight
Participants 1: Day 155
77.2 kilogram (kg)
Vital Signs: Weight
Participants 2: Day 1
89.0 kilogram (kg)
Vital Signs: Weight
Participants 2: Day 83
89.0 kilogram (kg)
Vital Signs: Weight
Participants 2: Day 125
92.2 kilogram (kg)
Vital Signs: Weight
Participants 2: Day 155
92.1 kilogram (kg)
Vital Signs: Weight
Participant 3: Day 1
40.8 kilogram (kg)
Vital Signs: Weight
Participants 3: Day 125
40.3 kilogram (kg)

SECONDARY outcome

Timeframe: Baseline up to 235 days

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

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

Outcome measures

Outcome measures
Measure
Experimental: Evobrutinib + Avonex® Matched Placebo
n=2 Participants
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.
Active Comparator: Avonex® + Evobrutinib Matched Placebo
n=1 Participants
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.
Number of Participants With Abnormal Lab Values
0 Participants
0 Participants

SECONDARY outcome

Timeframe: Baseline up to 235 days

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

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

Outcome measures

Outcome measures
Measure
Experimental: Evobrutinib + Avonex® Matched Placebo
n=2 Participants
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.
Active Comparator: Avonex® + Evobrutinib Matched Placebo
n=1 Participants
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.
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
0 Participants
0 Participants

SECONDARY outcome

Timeframe: At Day 1, 83, 125 and 155

Population: 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.

Absolute concentrations of Immunoglobulin (Ig) A was reported.

Outcome measures

Outcome measures
Measure
Experimental: Evobrutinib + Avonex® Matched Placebo
n=2 Participants
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.
Active Comparator: Avonex® + Evobrutinib Matched Placebo
n=1 Participants
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.
Absolute Concentrations of Immunoglobulin (Ig) A Level
Participant 1: Day 1
2.09 grams per liter (g/L)
Absolute Concentrations of Immunoglobulin (Ig) A Level
Participant 1: Day 83
2.64 grams per liter (g/L)
Absolute Concentrations of Immunoglobulin (Ig) A Level
Participant 1: Day 125
2.64 grams per liter (g/L)
Absolute Concentrations of Immunoglobulin (Ig) A Level
Participant 1: Day 155
2.78 grams per liter (g/L)
Absolute Concentrations of Immunoglobulin (Ig) A Level
Participant 2: Day 1
1.64 grams per liter (g/L)
Absolute Concentrations of Immunoglobulin (Ig) A Level
Participant 2: Day 83
1.85 grams per liter (g/L)
Absolute Concentrations of Immunoglobulin (Ig) A Level
Participant 2: Day 125
2.2 grams per liter (g/L)
Absolute Concentrations of Immunoglobulin (Ig) A Level
Participant 2: Day 155
2.15 grams per liter (g/L)
Absolute Concentrations of Immunoglobulin (Ig) A Level
Participant 3: Day 1
2.09 grams per liter (g/L)
Absolute Concentrations of Immunoglobulin (Ig) A Level
Participant 3: Day 125
1.84 grams per liter (g/L)

SECONDARY outcome

Timeframe: At Day 1, 83, 125 and 155

Population: 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.

Absolute concentrations of Immunoglobulin (Ig) E was reported.

Outcome measures

Outcome measures
Measure
Experimental: Evobrutinib + Avonex® Matched Placebo
n=2 Participants
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.
Active Comparator: Avonex® + Evobrutinib Matched Placebo
n=1 Participants
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.
Absolute Concentrations of Immunoglobulin (Ig) E Level
Participant 1: Day 83
108 International unit per milliliter(IU/mL)
Absolute Concentrations of Immunoglobulin (Ig) E Level
Participant 1: Day 125
55.2 International unit per milliliter(IU/mL)
Absolute Concentrations of Immunoglobulin (Ig) E Level
Participant 1: Day 155
71.9 International unit per milliliter(IU/mL)
Absolute Concentrations of Immunoglobulin (Ig) E Level
Participant 1: Day 1
61 International unit per milliliter(IU/mL)
Absolute Concentrations of Immunoglobulin (Ig) E Level
Participant 2: Day 1
10.7 International unit per milliliter(IU/mL)
Absolute Concentrations of Immunoglobulin (Ig) E Level
Participant 2: Day 83
12.3 International unit per milliliter(IU/mL)
Absolute Concentrations of Immunoglobulin (Ig) E Level
Participant 2: Day 125
14.9 International unit per milliliter(IU/mL)
Absolute Concentrations of Immunoglobulin (Ig) E Level
Participant 2: Day 155
11.4 International unit per milliliter(IU/mL)
Absolute Concentrations of Immunoglobulin (Ig) E Level
Participant 3: Day 1
27.6 International unit per milliliter(IU/mL)
Absolute Concentrations of Immunoglobulin (Ig) E Level
Participant 3: Day 125
23.5 International unit per milliliter(IU/mL)

SECONDARY outcome

Timeframe: At Day 1, 83, 125 and 155

Population: 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.

Absolute concentrations of Immunoglobulin (Ig) G was reported.

Outcome measures

Outcome measures
Measure
Experimental: Evobrutinib + Avonex® Matched Placebo
n=2 Participants
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.
Active Comparator: Avonex® + Evobrutinib Matched Placebo
n=1 Participants
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.
Absolute Concentrations of Immunoglobulin (Ig) G Level
Participant 1: Day 125
19.34 grams per liter (g/L)
Absolute Concentrations of Immunoglobulin (Ig) G Level
Participant 1: Day 155
19.62 grams per liter (g/L)
Absolute Concentrations of Immunoglobulin (Ig) G Level
Participant 2: Day 1
9.46 grams per liter (g/L)
Absolute Concentrations of Immunoglobulin (Ig) G Level
Participant 2: Day 83
10.26 grams per liter (g/L)
Absolute Concentrations of Immunoglobulin (Ig) G Level
Participant 1: Day 1
16.49 grams per liter (g/L)
Absolute Concentrations of Immunoglobulin (Ig) G Level
Participant 1: Day 83
21.77 grams per liter (g/L)
Absolute Concentrations of Immunoglobulin (Ig) G Level
Participant 2: Day 125
11.23 grams per liter (g/L)
Absolute Concentrations of Immunoglobulin (Ig) G Level
Participant 2: Day 155
11.18 grams per liter (g/L)
Absolute Concentrations of Immunoglobulin (Ig) G Level
Participant 3: Day 1
12.52 grams per liter (g/L)
Absolute Concentrations of Immunoglobulin (Ig) G Level
Participant 3: Day 125
11.41 grams per liter (g/L)

SECONDARY outcome

Timeframe: At Day 1, 83, 125 and 155

Population: 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.

Absolute concentrations of Immunoglobulin (Ig) M was reported.

Outcome measures

Outcome measures
Measure
Experimental: Evobrutinib + Avonex® Matched Placebo
n=2 Participants
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.
Active Comparator: Avonex® + Evobrutinib Matched Placebo
n=1 Participants
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.
Absolute Concentrations of Immunoglobulin (Ig) M Level
Participant 1: Day 1
0.97 grams per liter (g/L)
Absolute Concentrations of Immunoglobulin (Ig) M Level
Participant 1: Day 83
1.47 grams per liter (g/L)
Absolute Concentrations of Immunoglobulin (Ig) M Level
Participant 1: Day 125
1.35 grams per liter (g/L)
Absolute Concentrations of Immunoglobulin (Ig) M Level
Participant 1: Day 155
1.43 grams per liter (g/L)
Absolute Concentrations of Immunoglobulin (Ig) M Level
Participant 2: Day 1
1.08 grams per liter (g/L)
Absolute Concentrations of Immunoglobulin (Ig) M Level
Participant 2: Day 83
0.84 grams per liter (g/L)
Absolute Concentrations of Immunoglobulin (Ig) M Level
Participant 2: Day 125
0.78 grams per liter (g/L)
Absolute Concentrations of Immunoglobulin (Ig) M Level
Participant 2: Day 155
1 grams per liter (g/L)
Absolute Concentrations of Immunoglobulin (Ig) M Level
Participant 3: Day 1
2.22 grams per liter (g/L)
Absolute Concentrations of Immunoglobulin (Ig) M Level
Participant 3: 125
1.91 grams per liter (g/L)

SECONDARY outcome

Timeframe: At Day 1, 83, 125 and 155

Population: 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.

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

Outcome measures

Outcome measures
Measure
Experimental: Evobrutinib + Avonex® Matched Placebo
n=2 Participants
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.
Active Comparator: Avonex® + Evobrutinib Matched Placebo
n=1 Participants
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.
Change From Baseline in Immunoglobulin (Ig) A Level
Participant 2: Day 125
0.56 grams per liter (g/L)
Change From Baseline in Immunoglobulin (Ig) A Level
Participant 2: Day 155
0.51 grams per liter (g/L)
Change From Baseline in Immunoglobulin (Ig) A Level
Participant 3: Day 125
-0.25 grams per liter (g/L)
Change From Baseline in Immunoglobulin (Ig) A Level
Participant 1: Day 83
0.55 grams per liter (g/L)
Change From Baseline in Immunoglobulin (Ig) A Level
Participant 1: Day 125
0.55 grams per liter (g/L)
Change From Baseline in Immunoglobulin (Ig) A Level
Participant 1: Day 155
0.69 grams per liter (g/L)
Change From Baseline in Immunoglobulin (Ig) A Level
Participant 2: Day 83
0.21 grams per liter (g/L)

SECONDARY outcome

Timeframe: At Day 1, 83, 125 and 155

Population: 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.

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

Outcome measures

Outcome measures
Measure
Experimental: Evobrutinib + Avonex® Matched Placebo
n=2 Participants
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.
Active Comparator: Avonex® + Evobrutinib Matched Placebo
n=1 Participants
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.
Change From Baseline in Immunoglobulin (Ig) E Level
Participant 1: Day 83
47 International unit per milliliter(IU/mL)
Change From Baseline in Immunoglobulin (Ig) E Level
Participant 1: Day 125
-5.8 International unit per milliliter(IU/mL)
Change From Baseline in Immunoglobulin (Ig) E Level
Participant 1: Day 155
10.9 International unit per milliliter(IU/mL)
Change From Baseline in Immunoglobulin (Ig) E Level
Participant 2: Day 83
1.6 International unit per milliliter(IU/mL)
Change From Baseline in Immunoglobulin (Ig) E Level
Participant 2: Day 125
4.2 International unit per milliliter(IU/mL)
Change From Baseline in Immunoglobulin (Ig) E Level
Participant 2: Day 155
0.7 International unit per milliliter(IU/mL)
Change From Baseline in Immunoglobulin (Ig) E Level
Participant 3: Day 125
-4.1 International unit per milliliter(IU/mL)

SECONDARY outcome

Timeframe: At Day 1, 83, 125 and 155

Population: 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.

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

Outcome measures

Outcome measures
Measure
Experimental: Evobrutinib + Avonex® Matched Placebo
n=2 Participants
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.
Active Comparator: Avonex® + Evobrutinib Matched Placebo
n=1 Participants
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.
Change From Baseline in Immunoglobulin (Ig) G Level
Participant 3: Day 125
-1.11 grams per liter (g/L)
Change From Baseline in Immunoglobulin (Ig) G Level
Participant 1: Day 83
5.28 grams per liter (g/L)
Change From Baseline in Immunoglobulin (Ig) G Level
Participant 1: Day 125
2.85 grams per liter (g/L)
Change From Baseline in Immunoglobulin (Ig) G Level
Participant 1: Day 155
3.13 grams per liter (g/L)
Change From Baseline in Immunoglobulin (Ig) G Level
Participant 2: Day 83
0.8 grams per liter (g/L)
Change From Baseline in Immunoglobulin (Ig) G Level
Participant 2: Day 125
1.77 grams per liter (g/L)
Change From Baseline in Immunoglobulin (Ig) G Level
Participant 2: Day 155
1.72 grams per liter (g/L)

SECONDARY outcome

Timeframe: At Day 1, 83, 125 and 155

Population: 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.

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

Outcome measures

Outcome measures
Measure
Experimental: Evobrutinib + Avonex® Matched Placebo
n=2 Participants
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.
Active Comparator: Avonex® + Evobrutinib Matched Placebo
n=1 Participants
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.
Change From Baseline in Immunoglobulin (Ig) M Level
Participant 1: Day 83
0.5 grams per liter (g/L)
Change From Baseline in Immunoglobulin (Ig) M Level
Participant 1: Day 125
0.38 grams per liter (g/L)
Change From Baseline in Immunoglobulin (Ig) M Level
Participant 1: Day 155
0.46 grams per liter (g/L)
Change From Baseline in Immunoglobulin (Ig) M Level
Participant 2: Day 83
-0.24 grams per liter (g/L)
Change From Baseline in Immunoglobulin (Ig) M Level
Participant 2: Day 125
-0.3 grams per liter (g/L)
Change From Baseline in Immunoglobulin (Ig) M Level
Participant 2: Day 155
-0.08 grams per liter (g/L)
Change From Baseline in Immunoglobulin (Ig) M Level
Participant 3: Day 125
-0.31 grams per liter (g/L)

Adverse Events

Experimental: Evobrutinib + Avonex® Matched Placebo

Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths

Active Comparator: Avonex® + Evobrutinib Matched Placebo

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Experimental: Evobrutinib + Avonex® Matched Placebo
n=2 participants at risk
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.
Active Comparator: Avonex® + Evobrutinib Matched Placebo
n=1 participants at risk
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.
Investigations
Neutrophil count decreased
0.00%
0/2 • Baseline up to 235 days
SAF analysis set included all participants who were administered any dose of any study intervention.
100.0%
1/1 • Baseline up to 235 days
SAF analysis set included all participants who were administered any dose of any study intervention.
Nervous system disorders
Tension headache
0.00%
0/2 • Baseline up to 235 days
SAF analysis set included all participants who were administered any dose of any study intervention.
100.0%
1/1 • Baseline up to 235 days
SAF analysis set included all participants who were administered any dose of any study intervention.
Gastrointestinal disorders
Abdominal pain
0.00%
0/2 • Baseline up to 235 days
SAF analysis set included all participants who were administered any dose of any study intervention.
100.0%
1/1 • Baseline up to 235 days
SAF analysis set included all participants who were administered any dose of any study intervention.
Gastrointestinal disorders
Vomiting
0.00%
0/2 • Baseline up to 235 days
SAF analysis set included all participants who were administered any dose of any study intervention.
100.0%
1/1 • Baseline up to 235 days
SAF analysis set included all participants who were administered any dose of any study intervention.
General disorders
Drug eruption
50.0%
1/2 • Baseline up to 235 days
SAF analysis set included all participants who were administered any dose of any study intervention.
0.00%
0/1 • Baseline up to 235 days
SAF analysis set included all participants who were administered any dose of any study intervention.
General disorders
Influenza like illness
50.0%
1/2 • Baseline up to 235 days
SAF analysis set included all participants who were administered any dose of any study intervention.
0.00%
0/1 • Baseline up to 235 days
SAF analysis set included all participants who were administered any dose of any study intervention.
Musculoskeletal and connective tissue disorders
Pain in jaw
50.0%
1/2 • Baseline up to 235 days
SAF analysis set included all participants who were administered any dose of any study intervention.
0.00%
0/1 • Baseline up to 235 days
SAF analysis set included all participants who were administered any dose of any study intervention.
Nervous system disorders
Paraesthesia
50.0%
1/2 • Baseline up to 235 days
SAF analysis set included all participants who were administered any dose of any study intervention.
0.00%
0/1 • Baseline up to 235 days
SAF analysis set included all participants who were administered any dose of any study intervention.
Skin and subcutaneous tissue disorders
Tinea cruris
50.0%
1/2 • Baseline up to 235 days
SAF analysis set included all participants who were administered any dose of any study intervention.
0.00%
0/1 • Baseline up to 235 days
SAF analysis set included all participants who were administered any dose of any study intervention.
Skin and subcutaneous tissue disorders
Petechiae
50.0%
1/2 • Baseline up to 235 days
SAF analysis set included all participants who were administered any dose of any study intervention.
0.00%
0/1 • Baseline up to 235 days
SAF analysis set included all participants who were administered any dose of any study intervention.

Additional Information

Communication Center

Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Phone: +49-6151-72-5200

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place