Trial Outcomes & Findings for Study of Evobrutinib in Participants With RMS (NCT NCT04032171)
NCT ID: NCT04032171
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.
TERMINATED
PHASE3
1 participants
At Week 96
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. A total of 950 participants were planned to be included in 1:1 to treatment with evobrutinib or Avonex, however only 1 participant was enrolled in evobrutinib due to early termination.
Participant milestones
| Measure |
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.
|
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
|
1
|
0
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
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.
|
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
|
1
|
0
|
Baseline Characteristics
Study of Evobrutinib in Participants With RMS
Baseline characteristics by cohort
| Measure |
Evobrutinib + Avonex® Matched Placebo
n=1 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.
|
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.
|
Total
n=1 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
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 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
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 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
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 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 96Population: Following analysis of open label extension (OLE) data from RMS phase 2 study (MS200527- 0086), it was determined that a change in active comparator warranted in phase 3 RMS comprised of trial MS200527-0074. Consequently, this trial terminated early, therefore, it was decided as per Statistical Analysis Plan not to report the efficacy data for this study.
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 weeksPopulation: Following analysis of open label extension (OLE) data from RMS phase 2 study (MS200527- 0086), it was determined that a change in active comparator warranted in phase 3 RMS comprised of trial MS200527-0074. Consequently, this trial terminated early, therefore, it was decided as per Statistical Analysis Plan not to report the efficacy data for this study.
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 weeksPopulation: Following analysis of open label extension (OLE) data from RMS phase 2 study (MS200527- 0086), it was determined that a change in active comparator warranted in phase 3 RMS comprised of trial MS200527-0074. Consequently, this trial terminated early, therefore, it was decided as per Statistical Analysis Plan not to report the efficacy data for this study.
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 96Population: Following analysis of open label extension (OLE) data from RMS phase 2 study (MS200527- 0086), it was determined that a change in active comparator warranted in phase 3 RMS comprised of trial MS200527-0074. Consequently, this trial terminated early, therefore, it was decided as per Statistical Analysis Plan not to report the efficacy data for this study.
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 96Population: Following analysis of open label extension (OLE) data from RMS phase 2 study (MS200527- 0086), it was determined that a change in active comparator warranted in phase 3 RMS comprised of trial MS200527-0074. Consequently, this trial terminated early, therefore, it was decided as per Statistical Analysis Plan not to report the efficacy data for this study.
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 96Population: Following analysis of open label extension (OLE) data from RMS phase 2 study (MS200527- 0086), it was determined that a change in active comparator warranted in phase 3 RMS comprised of trial MS200527-0074. Consequently, this trial terminated early, therefore, it was decided as per Statistical Analysis Plan not to report the efficacy data for this study.
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 96Population: Following analysis of open label extension (OLE) data from RMS phase 2 study (MS200527- 0086), it was determined that a change in active comparator warranted in phase 3 RMS comprised of trial MS200527-0074. Consequently, this trial terminated early, therefore, it was decided as per Statistical Analysis Plan not to report the efficacy data for this study.
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 254 daysPopulation: 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 \& was serious, related to investigational medicinal product (IMP), or resulted in death, discontinuation, interruption or reduction of study therapy. TEAEs included both serious and non-serious TEAEs. AESIs included liver AEs (possible drug-induced, non-infectious, non-alcoholic and immune-mediated) infections (serious and opportunistic infections), lipase and amylase elevation, and seizure.
Outcome measures
| Measure |
Evobrutinib + Avonex® Matched Placebo
n=1 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.
|
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.
|
|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs)
Participants with TEAEs
|
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
|
—
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs)
Participants with AESIs
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Baseline up to 254 daysPopulation: Safety (SAF) analysis set included all participants who were administered any dose of any study intervention.
Adverse event (AE) was defined as any untoward medical occurrence in a participant, which does not necessarily have causal relationship with treatment. A serious AE was defined as an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged in participant hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs included both serious TEAEs and non-serious TEAEs. Severity of TEAEs were graded using NCI CTCAE v4.03 toxicity grades, as follows: Grade 1= Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death. Number of participants with TEAEs based on severity were reported.
Outcome measures
| Measure |
Evobrutinib + Avonex® Matched Placebo
n=1 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.
|
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.
|
|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)
Grade 1
|
1 Participants
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)
Grade 5
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: At Day 1, Week 2 unscheduled 1, Week 12 and Early Discontinuation (ED) (up to approximately 36 weeksPopulation: SAF analysis set included all participants who were administered any dose of any study intervention.
DBP and SBP were measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Outcome measures
| Measure |
Evobrutinib + Avonex® Matched Placebo
n=1 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.
|
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.
|
|---|---|---|
|
Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
DBP: Day 1
|
72 Millimeters of mercury (mmHg)
|
—
|
|
Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
DBP: Week 2 unscheduled 1
|
68 Millimeters of mercury (mmHg)
|
—
|
|
Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
DBP: Week 12
|
76 Millimeters of mercury (mmHg)
|
—
|
|
Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
DBP: ED (up to approximately 36 weeks)
|
84 Millimeters of mercury (mmHg)
|
—
|
|
Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
SBP: Day 1
|
124 Millimeters of mercury (mmHg)
|
—
|
|
Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
SBP: Week 2 unscheduled 1
|
119 Millimeters of mercury (mmHg)
|
—
|
|
Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
SBP: Week 12
|
130 Millimeters of mercury (mmHg)
|
—
|
|
Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
SBP:ED (up to approximately 36 weeks)
|
140 Millimeters of mercury (mmHg)
|
—
|
SECONDARY outcome
Timeframe: At Day 1, Week 2 unscheduled 1, Week 12 and Early Discontinuation ED (up to approximately 36 weeks)Population: SAF analysis set included all participants who were administered any dose of any study intervention.
Pulse rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Outcome measures
| Measure |
Evobrutinib + Avonex® Matched Placebo
n=1 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.
|
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.
|
|---|---|---|
|
Vital Signs: Pulse Rate
Pulse rate: Day 1
|
71 Beats per minute
|
—
|
|
Vital Signs: Pulse Rate
Pulse rate: Week 2 unscheduled 1
|
77 Beats per minute
|
—
|
|
Vital Signs: Pulse Rate
Pulse rate: Week 12
|
75 Beats per minute
|
—
|
|
Vital Signs: Pulse Rate
Pulse rate: ED (up to approximately 36 weeks)
|
80 Beats per minute
|
—
|
SECONDARY outcome
Timeframe: At Day 1, Week 2 unscheduled 1, Week 12 and Early Discontinuation ED (up to approximately 36 weeks)Population: SAF analysis set included all participants who were administered any dose of any study intervention.
Respiration rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Outcome measures
| Measure |
Evobrutinib + Avonex® Matched Placebo
n=1 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.
|
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.
|
|---|---|---|
|
Vital Signs: Respiratory Rate
Respiratory rate: ED (up to approximately 36 weeks)
|
14 Breaths Per Minute
|
—
|
|
Vital Signs: Respiratory Rate
Respiratory rate: Day 1
|
12 Breaths Per Minute
|
—
|
|
Vital Signs: Respiratory Rate
Respiratory rate: Week 2 unscheduled 1
|
18 Breaths Per Minute
|
—
|
|
Vital Signs: Respiratory Rate
Respiratory rate: Week 12
|
12 Breaths Per Minute
|
—
|
SECONDARY outcome
Timeframe: At Day 1, Week 2 unscheduled 1, Week 12 and Early Discontinuation (ED) (up to approximately 36 weeks)Population: SAF analysis set included all participants who were administered any dose of any study intervention.
Temperature was measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Outcome measures
| Measure |
Evobrutinib + Avonex® Matched Placebo
n=1 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.
|
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.
|
|---|---|---|
|
Vital Signs: Temperature
Day 1
|
36.4 Degree celsius
|
—
|
|
Vital Signs: Temperature
Week 2 unscheduled 1
|
36.7 Degree celsius
|
—
|
|
Vital Signs: Temperature
Week 12
|
36.9 Degree celsius
|
—
|
|
Vital Signs: Temperature
ED (up to approximately 36 weeks)
|
36.7 Degree celsius
|
—
|
SECONDARY outcome
Timeframe: At Day 1, Week 2 unscheduled 1, Week 12 and Early Discontinuation (up to approximately 36 weeks)Population: SAF analysis set included all participants who were administered any dose of any study intervention.
Outcome measures
| Measure |
Evobrutinib + Avonex® Matched Placebo
n=1 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.
|
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.
|
|---|---|---|
|
Vital Signs: Weight
Day 1
|
91.4 kilogram (kg)
|
—
|
|
Vital Signs: Weight
Week 2 unscheduled 1
|
92.3 kilogram (kg)
|
—
|
|
Vital Signs: Weight
Week 12
|
92.6 kilogram (kg)
|
—
|
|
Vital Signs: Weight
ED (up to approximately 36 weeks)
|
95.5 kilogram (kg)
|
—
|
SECONDARY outcome
Timeframe: Baseline up to 254 daysPopulation: 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
| Measure |
Evobrutinib + Avonex® Matched Placebo
n=1 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.
|
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.
|
|---|---|---|
|
Number of Participants With Abnormal Lab Values
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Baseline up to 254 daysPopulation: 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
| Measure |
Evobrutinib + Avonex® Matched Placebo
n=1 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.
|
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.
|
|---|---|---|
|
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: At Day 1 and Day 92Population: SAF analysis set included all participants who were administered any dose of any study intervention.
Absolute concentrations of Immunoglobulin (Ig) A was reported.
Outcome measures
| Measure |
Evobrutinib + Avonex® Matched Placebo
n=1 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.
|
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.
|
|---|---|---|
|
Absolute Concentrations of Immunoglobulin (Ig) A Level
Day 1
|
0.8 gram per liter (g/L)
|
—
|
|
Absolute Concentrations of Immunoglobulin (Ig) A Level
Day 92
|
0.92 gram per liter (g/L)
|
—
|
SECONDARY outcome
Timeframe: At Day 1 and Day 92Population: SAF analysis set included all participants who were administered any dose of any study intervention.
Absolute concentrations of Immunoglobulin (Ig) E was reported.
Outcome measures
| Measure |
Evobrutinib + Avonex® Matched Placebo
n=1 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.
|
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.
|
|---|---|---|
|
Absolute Concentrations of Immunoglobulin (Ig) G Level
Day 1
|
5.54 grams per liter (g/L)
|
—
|
|
Absolute Concentrations of Immunoglobulin (Ig) G Level
Day 92
|
6.11 grams per liter (g/L)
|
—
|
SECONDARY outcome
Timeframe: At Day 1 and Day 92Population: SAF analysis set included all participants who were administered any dose of any study intervention.
Absolute concentrations of Immunoglobulin (Ig) M was reported.
Outcome measures
| Measure |
Evobrutinib + Avonex® Matched Placebo
n=1 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.
|
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.
|
|---|---|---|
|
Absolute Concentrations of Immunoglobulin (Ig) M Level
Day 1
|
0.29 grams per liter (g/L)
|
—
|
|
Absolute Concentrations of Immunoglobulin (Ig) M Level
Day 92
|
0.25 grams per liter (g/L)
|
—
|
SECONDARY outcome
Timeframe: At Day 1 and Day 92Population: SAF analysis set included all participants who were administered any dose of any study intervention.
Absolute concentrations of Immunoglobulin (Ig) E was reported.
Outcome measures
| Measure |
Evobrutinib + Avonex® Matched Placebo
n=1 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.
|
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.
|
|---|---|---|
|
Absolute Concentrations of Immunoglobulin (Ig) E Level
Day 1
|
14.1 International units per milliliter
|
—
|
|
Absolute Concentrations of Immunoglobulin (Ig) E Level
Day 92
|
16.7 International units per milliliter
|
—
|
SECONDARY outcome
Timeframe: At Day 1 and Day 92Population: SAF analysis set included all participants who were administered any dose of any study intervention.
Change from baseline in immunoglobulin (Ig) A level was reported.
Outcome measures
| Measure |
Evobrutinib + Avonex® Matched Placebo
n=1 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.
|
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.
|
|---|---|---|
|
Change From Baseline in Immunoglobulin (Ig) A Level
|
0.12 gram per liter (g/L)
|
—
|
SECONDARY outcome
Timeframe: At Day 1 and Day 92Population: SAF analysis set included all participants who were administered any dose of any study intervention.
Change from baseline in immunoglobulin (Ig) E level was reported.
Outcome measures
| Measure |
Evobrutinib + Avonex® Matched Placebo
n=1 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.
|
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.
|
|---|---|---|
|
Change From Baseline in Immunoglobulin (Ig) E Level
|
2.6 International units per milliliter
|
—
|
SECONDARY outcome
Timeframe: At Day 1 and Day 92Population: SAF analysis set included all participants who were administered any dose of any study intervention.
Change from baseline in immunoglobulin (Ig) G level was reported.
Outcome measures
| Measure |
Evobrutinib + Avonex® Matched Placebo
n=1 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.
|
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.
|
|---|---|---|
|
Change From Baseline in Immunoglobulin (Ig) G Level
|
0.57 grams per liter (g/L)
|
—
|
SECONDARY outcome
Timeframe: At Day 1 and Day 92Population: SAF analysis set included all participants who were administered any dose of any study intervention.
Change from baseline in immunoglobulin (Ig) M level was reported.
Outcome measures
| Measure |
Evobrutinib + Avonex® Matched Placebo
n=1 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.
|
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.
|
|---|---|---|
|
Change From Baseline in Immunoglobulin (Ig) M Level
|
-0.04 grams per liter (g/L)
|
—
|
Adverse Events
Evobrutinib + Avonex® Matched Placebo
Avonex® + Evobrutinib Matched Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Evobrutinib + Avonex® Matched Placebo
n=1 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.
|
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.
|
|---|---|---|
|
Eye disorders
Dry eye
|
100.0%
1/1 • Baseline up to 254 days
Following analysis of open label extension (OLE) data from RMS phase 2 study (MS200527- 0086), it was determined that a change in active comparator warranted in phase 3 RMS comprised of trial MS200527-0074. Consequently, this trial terminated early, therefore no participants enrolled in Avonex® + Evobrutinib matched Placebo arm.
|
—
0/0 • Baseline up to 254 days
Following analysis of open label extension (OLE) data from RMS phase 2 study (MS200527- 0086), it was determined that a change in active comparator warranted in phase 3 RMS comprised of trial MS200527-0074. Consequently, this trial terminated early, therefore no participants enrolled in Avonex® + Evobrutinib matched Placebo arm.
|
|
Nervous system disorders
Peripheral edema
|
100.0%
1/1 • Baseline up to 254 days
Following analysis of open label extension (OLE) data from RMS phase 2 study (MS200527- 0086), it was determined that a change in active comparator warranted in phase 3 RMS comprised of trial MS200527-0074. Consequently, this trial terminated early, therefore no participants enrolled in Avonex® + Evobrutinib matched Placebo arm.
|
—
0/0 • Baseline up to 254 days
Following analysis of open label extension (OLE) data from RMS phase 2 study (MS200527- 0086), it was determined that a change in active comparator warranted in phase 3 RMS comprised of trial MS200527-0074. Consequently, this trial terminated early, therefore no participants enrolled in Avonex® + Evobrutinib matched Placebo arm.
|
|
Hepatobiliary disorders
Hypercholesterolemia
|
100.0%
1/1 • Baseline up to 254 days
Following analysis of open label extension (OLE) data from RMS phase 2 study (MS200527- 0086), it was determined that a change in active comparator warranted in phase 3 RMS comprised of trial MS200527-0074. Consequently, this trial terminated early, therefore no participants enrolled in Avonex® + Evobrutinib matched Placebo arm.
|
—
0/0 • Baseline up to 254 days
Following analysis of open label extension (OLE) data from RMS phase 2 study (MS200527- 0086), it was determined that a change in active comparator warranted in phase 3 RMS comprised of trial MS200527-0074. Consequently, this trial terminated early, therefore no participants enrolled in Avonex® + Evobrutinib matched Placebo arm.
|
Additional Information
Communication Center
Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place