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A Phase II Study of M2951 in SLE

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ClinicalTrials.gov Identifier: NCT02975336
Recruitment Status : Terminated (Study is completed; primary analysis completed.)
First Posted : November 29, 2016
Results First Posted : December 17, 2020
Last Update Posted : April 12, 2021
Sponsor:
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Systemic Lupus Erythematosus
Interventions Drug: Placebo
Drug: M2951
Enrollment 469
Recruitment Details A total of 1053 participants with Systemic Lupus Erythematosus (SLE) were screened. Out of which 469 participants were randomized in ratio of 1:1:1:1 to 1 of 4 treatment groups: Placebo; M2951 25mg QD, M2951 75 mg QD and M2951 50 mg BID. 283 out of 348 participants that completed Double-Blind Placebo-Controlled (DBPC) period, entered the Long-Term Extension (LTE) period of study.
Pre-assignment Details  
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID LTE: Placebo/ M2951 50 mg BID LTE Period: M2951 25 mg QD/ M2951 50 mg BID LTE Period: M2951 75 mg QD/ M2951 50 mg BID LTE: M2951 50 mg BID/ M2951 50 mg BID
Hide Arm/Group Description Participants received placebo matched to M2951 orally for 52 weeks. Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks. Participants received 75 mg of M2951 orally QD for 52 weeks. Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks. Participants who received Placebo in DBPC period were switched to receive 50 mg M2951 orally BID in LTE period for 104 weeks. Participants who received 25 mg of M2951 orally QD in DBPC period were switched to receive 50 mg M2951 orally BID in LTE period for 104 weeks. Participants who received 75 mg of M2951 orally QD in DBPC period were switched to receive 50 mg M2951 orally BID in LTE period for 104 weeks. Participants who received 50 mg of M2951 orally BID in DBPC period continued to receive same dose of M2951 orally BID in LTE period for 104 weeks.
Period Title: DBPC (52 Weeks)
Started 117 118 117 117 0 0 0 0
Completed 85 89 90 84 0 0 0 0
Not Completed 32 29 27 33 0 0 0 0
Reason Not Completed
Adverse Event             16             17             13             18             0             0             0             0
Lost to Follow-up             2             1             2             4             0             0             0             0
Protocol Violation             4             1             3             1             0             0             0             0
Lack of Efficacy             4             4             2             3             0             0             0             0
Withdrawal by Subject             1             0             1             3             0             0             0             0
Premature termination of the study             5             6             6             4             0             0             0             0
Period Title: LTE (104 Weeks)
Started 0 0 0 0 62 69 80 72
Completed 0 0 0 0 0 0 0 0
Not Completed 0 0 0 0 62 69 80 72
Reason Not Completed
Adverse Event             0             0             0             0             7             4             2             0
Lost to Follow-up             0             0             0             0             0             1             0             0
Lack of Efficacy             0             0             0             0             0             1             2             0
Other             0             0             0             0             55             63             76             72
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID Total
Hide Arm/Group Description Participants received placebo matched to M2951 orally for 52 weeks. Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks. Participants received 75 mg of M2951 orally QD for 52 weeks. Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks. Total of all reporting groups
Overall Number of Baseline Participants 117 118 117 117 469
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 117 participants 118 participants 117 participants 117 participants 469 participants
40.2  (12.49) 38.8  (12.45) 41.5  (12.52) 42.2  (11.78) 40.7  (12.34)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 117 participants 118 participants 117 participants 117 participants 469 participants
Female
110
  94.0%
112
  94.9%
111
  94.9%
112
  95.7%
445
  94.9%
Male
7
   6.0%
6
   5.1%
6
   5.1%
5
   4.3%
24
   5.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 117 participants 118 participants 117 participants 117 participants 469 participants
Hispanic or Latino
45
  38.5%
51
  43.2%
47
  40.2%
42
  35.9%
185
  39.4%
Not Hispanic or Latino
72
  61.5%
67
  56.8%
70
  59.8%
75
  64.1%
284
  60.6%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 117 participants 118 participants 117 participants 117 participants 469 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
23
  19.7%
17
  14.4%
21
  17.9%
13
  11.1%
74
  15.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
10
   8.5%
12
  10.2%
11
   9.4%
12
  10.3%
45
   9.6%
White
66
  56.4%
73
  61.9%
68
  58.1%
83
  70.9%
290
  61.8%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
18
  15.4%
16
  13.6%
17
  14.5%
9
   7.7%
60
  12.8%
1.Primary Outcome
Title DBPC Period: Number of Participants With Response Based on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Week 52
Hide Description SRI-4 response was defined as greater than or equal to (>=) 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score, no new British Isles Lupus Assessment Group (BILAG) A and no more than 1 new BILAG B domain score, no worsening (less than 10 percent increase) from baseline in Physician's Global Assessment of Disease Activity (PGA) and no treatment failure. SLEDAI-2K assessment consists of 24 items with total score of 0(no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to Systemic Lupus Erythematosus (SLE) divided into 9 organ systems. For each organ system A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. The PGA assess disease activity on a visual analogue scale =from 0(very well) to 100(very poor).
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The modified Intent To Treat (mITT) analysis set included all randomized participants who had received at least one dose of Investigational Medicinal Product (IMP) [Evobrutinib or placebo] and have at least one Baseline and one post Baseline disease assessment (among the following: Systemic Lupus Erythematosus Disease Activity Index flare index [SFI], SLEDAI 2K, PGA, BILAG 2004, Cutaneous Lupus Erythematosus Disease Area and Severity Index [CLASI]).
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 114 115 116 114
Measure Type: Count of Participants
Unit of Measure: Participants
52
  45.6%
64
  55.7%
60
  51.7%
55
  48.2%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5462
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.55
Confidence Interval (2-Sided) 95%
0.91 to 2.64
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5462
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.29
Confidence Interval (2-Sided) 95%
0.76 to 2.18
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5462
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.13
Confidence Interval (2-Sided) 95%
0.67 to 1.93
Estimation Comments [Not Specified]
2.Primary Outcome
Title DBPC Period: Number of Participants With Response Based on Systemic Lupus Erythematosus Responder Index 6 (SRI-6) at Week 52
Hide Description SRI-6 response was defined as >= 6-point reduction in SLEDAI-2K total score, no new BILAG A and no more than 1 new BILAG B domain score and no worsening (less than 10 percent increase) from baseline in Physician's Global Assessment of Disease Activity (PGA) and treatment failure. SLEDAI-2K assessment consists of 24 items with total score of 0 (no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to SLE, divided into 9 organ systems. For each organ system :A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. The PGA assess disease activity on a visual analogue scale =from 0(very well) to 100(very poor).
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set included all randomized participants who had received at least one dose of IMP (Evobrutinib or placebo) and have at least one Baseline and one post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI. Here, "overall number of participants analyzed" signifies those participants who achieved SLEDAI-2K total score >= 10 at screening (High Disease Activity [HDA] participants).
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 56 54 65 55
Measure Type: Count of Participants
Unit of Measure: Participants
22
  39.3%
27
  50.0%
30
  46.2%
24
  43.6%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5462
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.50
Confidence Interval (2-Sided) 95%
0.69 to 3.24
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5462
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.42
Confidence Interval (2-Sided) 95%
0.68 to 2.97
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5462
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.27
Confidence Interval (2-Sided) 95%
0.59 to 2.75
Estimation Comments [Not Specified]
3.Primary Outcome
Title DBPC Period: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)
Hide Description 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: events between first dose of study drug that were absent before treatment/that worsened relative to pre-treatment state up to 56 weeks. TEAEs included both serious TEAEs and non-serious TEAEs. Number of participants with TEAEs and serious TEAEs were reported.
Time Frame Baseline up to Week 56
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo).
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 117 118 117 117
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAEs
96
  82.1%
103
  87.3%
100
  85.5%
99
  84.6%
Any serious TEAE
10
   8.5%
13
  11.0%
11
   9.4%
9
   7.7%
4.Primary Outcome
Title DBPC Period: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)
Hide Description 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 by severity were reported.
Time Frame Baseline up to Week 56
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo).
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 117 118 117 117
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 1
76
  65.0%
80
  67.8%
79
  67.5%
76
  65.0%
Grade 2
63
  53.8%
77
  65.3%
72
  61.5%
78
  66.7%
Grade 3
24
  20.5%
29
  24.6%
24
  20.5%
21
  17.9%
Grade 4
1
   0.9%
1
   0.8%
0
   0.0%
2
   1.7%
Grade 5
0
   0.0%
1
   0.8%
1
   0.9%
0
   0.0%
5.Primary Outcome
Title DBPC Period: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Hide Description Vital signs included body temperature, systolic and diastolic blood pressure, pulse rate, respiratory rate, weight and height. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in vital signs were reported.
Time Frame Baseline up to Week 56
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo).
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 117 118 117 117
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
6.Primary Outcome
Title DBPC Period: Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings
Hide Description 12-lead ECG recordings included rhythm, heart rate (as measured by RR interval), PR interval, QRS duration, and QT interval. The corrected QT interval (QTcF) was calculated using Fridericia's formula. 12-lead ECG recordings were obtained after the participants have rested for at least 10 minutes in semisupine position. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in 12-lead ECG findings were reported.
Time Frame Baseline up to Week 56
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo).
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 117 118 117 117
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
7.Primary Outcome
Title DBPC Period: Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Hide Description Laboratory investigation included hematology, biochemistry, urinalysis and coagulation. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in laboratory parameters were reported.
Time Frame Baseline up to Week 56
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo).
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 117 118 117 117
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
8.Primary Outcome
Title DBPC Period: Mean Absolute Value of Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2
Hide Description Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 2.
Time Frame Week 2
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 114 116 115 113
Mean (Standard Deviation)
Unit of Measure: gram per liter (g/L)
IgG 14.56  (5.367) 13.75  (4.652) 14.37  (5.536) 12.81  (3.847)
IgA 2.62  (1.207) 2.75  (1.374) 2.78  (1.328) 2.66  (1.137)
IgM 1.12  (0.662) 1.22  (0.890) 1.09  (0.697) 1.18  (0.776)
9.Primary Outcome
Title DBPC Period: Mean Absolute Value of Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 4
Hide Description Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 4.
Time Frame Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 114 114 114 115
Mean (Standard Deviation)
Unit of Measure: gram per liter (g/L)
IgG 14.92  (5.497) 13.60  (4.590) 14.21  (4.828) 12.73  (3.771)
IgA 2.71  (1.284) 2.73  (1.349) 2.82  (1.293) 2.64  (1.109)
IgM 1.12  (0.699) 1.18  (0.824) 1.06  (0.676) 1.16  (0.745)
10.Primary Outcome
Title DBPC Period: Mean Absolute Value of Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 12
Hide Description Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 12.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 110 106 110 105
Mean (Standard Deviation)
Unit of Measure: gram per liter (g/L)
IgG: 14.91  (5.312) 12.92  (4.332) 13.64  (4.035) 12.38  (3.520)
IgA 2.72  (1.321) 2.73  (1.340) 2.88  (1.363) 2.68  (1.021)
IgM 1.11  (0.683) 1.05  (0.700) 0.95  (0.610) 1.02  (0.695)
11.Primary Outcome
Title DBPC Period: Mean Absolute Value of Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 24
Hide Description Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 24.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 96 97 101 96
Mean (Standard Deviation)
Unit of Measure: gram per liter (g/L)
IgG 15.01  (5.190) 13.75  (4.783) 13.79  (4.165) 12.86  (3.725)
IgA 2.79  (1.430) 2.89  (1.460) 2.98  (1.391) 2.78  (1.091)
IgM 1.07  (0.609) 1.01  (0.686) 0.89  (0.583) 0.98  (0.656)
12.Primary Outcome
Title DBPC Period: Mean Absolute Value of Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 36
Hide Description Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 36.
Time Frame Week 36
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 92 91 97 86
Mean (Standard Deviation)
Unit of Measure: gram per liter (g/L)
IgG 14.81  (5.217) 13.54  (4.242) 13.67  (3.934) 12.65  (3.480)
IgA 2.72  (1.378) 2.89  (1.418) 3.01  (1.420) 2.86  (1.073)
IgM 1.06  (0.630) 1.01  (0.669) 0.85  (0.541) 0.95  (0.656)
13.Primary Outcome
Title DBPC Period: Mean Absolute Value of Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 52
Hide Description Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 52
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and Number Analyzed" signified those participants who were evaluable for the specified category at given time points.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 78 83 85 76
Mean (Standard Deviation)
Unit of Measure: gram per liter (g/L)
IgG Number Analyzed 78 participants 83 participants 85 participants 76 participants
15.21  (5.105) 13.90  (4.087) 14.32  (4.542) 13.01  (3.723)
IgA Number Analyzed 78 participants 83 participants 85 participants 76 participants
2.82  (1.438) 2.95  (1.596) 3.17  (1.596) 2.95  (1.159)
IgM Number Analyzed 78 participants 83 participants 84 participants 76 participants
1.08  (0.624) 0.94  (0.645) 0.82  (0.487) 0.96  (0.670)
14.Primary Outcome
Title DBPC Period: Mean Absolute Value of Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 56
Hide Description Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 56
Time Frame Week 56
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 37 36 31 33
Mean (Standard Deviation)
Unit of Measure: gram per liter (g/L)
IgG 14.82  (5.504) 14.25  (4.435) 14.25  (4.626) 13.12  (4.507)
IgA 2.95  (1.549) 3.01  (1.459) 2.89  (1.655) 3.03  (1.164)
IgM 1.11  (0.642) 1.01  (0.601) 0.95  (0.624) 1.31  (0.869)
15.Primary Outcome
Title DBPC Period: Mean Absolute Total B Cell Count at Week 4
Hide Description Mean total B cell count were assessed. Flow cytometry analysis of lymphocyte populations using four-color fluorescence activated cell sorting was performed for the analysis of B cell counts.
Time Frame Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 98 99 99 99
Mean (Standard Deviation)
Unit of Measure: Cells per microliter
150  (126.9) 236  (197.4) 296  (243.8) 229  (232.9)
16.Primary Outcome
Title DBPC Period: Mean Absolute Total B Cell Count at Week 24
Hide Description Mean absolute total B cell count were assessed. Flow cytometry analysis of lymphocyte populations using four-color fluorescence activated cell sorting was performed for the analysis of B cell counts.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 89 90 87 88
Mean (Standard Deviation)
Unit of Measure: Cells per microliter
161  (125.8) 184  (152.6) 204  (158.3) 151  (129.2)
17.Primary Outcome
Title DBPC Period: Mean Absolute Total B Cell Count at Week 52
Hide Description Mean absolute total B cell count were assessed. Flow cytometry analysis of lymphocyte populations using four-color fluorescence activated cell sorting was performed for the analysis of B cell counts.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 68 66 76 66
Mean (Standard Deviation)
Unit of Measure: Cells per microliter
169  (121.9) 167  (168.7) 180  (170.7) 119  (84.1)
18.Primary Outcome
Title DBPC Period: Mean Absolute Total B Cell Count at Week 56
Hide Description Mean absolute total B cell count were assessed. Flow cytometry analysis of lymphocyte populations using four-color fluorescence activated cell sorting was performed for the analysis of B cell counts.
Time Frame Week 56
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 35 30 27 30
Mean (Standard Deviation)
Unit of Measure: Cells per microliter
164  (113.3) 129  (100.0) 156  (127.1) 104  (71.9)
19.Primary Outcome
Title DBPC Period: Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2
Hide Description Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
Time Frame Baseline and Week 2
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 114 116 115 113
Mean (Standard Deviation)
Unit of Measure: gram per liter (g/L)
IgG -0.51  (1.726) -0.06  (1.361) -0.15  (1.772) -0.40  (1.025)
IgA -0.11  (0.435) -0.04  (0.431) -0.01  (0.381) -0.03  (0.268)
IgM 0.00  (0.197) -0.05  (0.194) -0.04  (0.155) -0.07  (0.116)
20.Primary Outcome
Title DBPC Period: Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 4
Hide Description Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
Time Frame Baseline and Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 114 114 114 115
Mean (Standard Deviation)
Unit of Measure: gram per liter (g/L)
IgG -0.26  (1.760) -0.16  (1.463) -0.24  (1.657) -0.45  (1.150)
IgA -0.01  (0.205) -0.04  (0.334) 0.03  (0.447) -0.03  (0.301)
IgM 0.01  (0.195) -0.09  (0.175) -0.07  (0.192) -0.08  (0.159)
21.Primary Outcome
Title DBPC Period: Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 12
Hide Description Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 110 106 110 105
Mean (Standard Deviation)
Unit of Measure: gram per liter (g/L)
IgG -0.36  (2.073) -0.62  (1.827) -0.72  (2.552) -0.93  (1.640)
IgA 0.00  (0.325) -0.02  (0.360) 0.06  (0.518) -0.03  (0.340)
IgM -0.01  (0.194) -0.20  (0.301) -0.18  (0.277) -0.20  (0.250)
22.Primary Outcome
Title DBPC Period: Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 24
Hide Description Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 96 97 101 96
Mean (Standard Deviation)
Unit of Measure: gram per liter (g/L)
IgG -0.21  (2.318) 0.11  (2.234) -0.46  (2.912) -0.57  (2.363)
IgA 0.06  (0.332) 0.14  (0.390) 0.19  (0.565) 0.04  (0.563)
IgM -0.01  (0.264) -0.23  (0.369) -0.23  (0.321) -0.25  (0.346)
23.Primary Outcome
Title DBPC Period: Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 36
Hide Description Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
Time Frame Baseline and Week 36
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 92 91 97 86
Mean (Standard Deviation)
Unit of Measure: gram per liter (g/L)
IgG -0.15  (2.130) 0.02  (2.487) -0.43  (2.572) -0.69  (2.189)
IgA -0.02  (0.361) 0.22  (0.453) 0.24  (0.583) 0.08  (0.459)
IgM -0.04  (0.255) -0.25  (0.416) -0.25  (0.284) -0.28  (0.392)
24.Primary Outcome
Title DBPC Period: Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 52
Hide Description Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
Time Frame Baseline and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 78 83 85 76
Mean (Standard Deviation)
Unit of Measure: gram per liter (g/L)
IgG Number Analyzed 78 participants 83 participants 85 participants 76 participants
0.41  (2.898) 0.29  (2.361) 0.35  (2.688) -0.31  (2.344)
IgA Number Analyzed 78 participants 83 participants 85 participants 76 participants
0.19  (0.420) 0.32  (0.492) 0.39  (0.767) 0.18  (0.469)
IgM Number Analyzed 78 participants 83 participants 84 participants 76 participants
-0.02  (0.235) -0.25  (0.303) -0.21  (0.318) -0.33  (0.456)
25.Primary Outcome
Title DBPC Period: Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 56
Hide Description Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
Time Frame Baseline and Week 56
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 37 36 31 33
Mean (Standard Deviation)
Unit of Measure: gram per liter (g/L)
IgG 0.74  (2.907) 1.06  (2.607) 0.74  (1.987) -0.40  (2.823)
IgA 0.23  (0.468) 0.48  (0.600) 0.35  (0.488) 0.26  (0.498)
IgM 0.01  (0.266) -0.15  (0.219) -0.11  (0.225) -0.21  (0.488)
26.Primary Outcome
Title DBPC Period: Change From Baseline in Total B Cell Count at Week 4
Hide Description Change from baseline in Total B cell count were assessed. Flow cytometry analysis of lymphocyte populations using four-color fluorescence-activated cell sorting was performed for the analysis of B cell counts.
Time Frame Baseline and Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 90 88 88 91
Mean (Standard Deviation)
Unit of Measure: Cells per microliter
-5  (93.7) 65  (146.6) 87  (146.2) 67  (109.1)
27.Primary Outcome
Title DBPC Period: Change From Baseline in Total B Cell Count at Week 24
Hide Description Change from baseline in Total B cell count were assessed. Flow cytometry analysis of lymphocyte populations using four-color fluorescence-activated cell sorting was performed for the analysis of B cell counts.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 80 82 73 81
Mean (Standard Deviation)
Unit of Measure: Cells per microliter
2  (98.1) 5  (112.0) 3  (103.2) -7  (134.7)
28.Primary Outcome
Title DBPC Period: Change From Baseline in Total B Cell Count at Week 52
Hide Description Change from baseline in Total B cell count were assessed. Flow cytometry analysis of lymphocyte populations using four-color fluorescence-activated cell sorting was performed for the analysis of B cell counts.
Time Frame Baseline and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 57 60 63 60
Mean (Standard Deviation)
Unit of Measure: Cells per microliter
-14  (103.0) -19  (133.3) -14  (147.5) -52  (215.7)
29.Primary Outcome
Title DBPC Period: Change From Baseline in Total B Cell Count at Week 56
Hide Description Change from baseline in Total B cell count were assessed. Flow cytometry analysis of lymphocyte populations using four-color fluorescence-activated cell sorting was performed for the analysis of B cell counts.
Time Frame Baseline and Week 56
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 30 27 24 24
Mean (Standard Deviation)
Unit of Measure: Cells per microliter
7  (96.2) -70  (138.2) -75  (192.1) -48  (85.8)
30.Secondary Outcome
Title DBPC Period: Time to First Severe British Isles Lupus Assessment Group (BILAG) A Flare
Hide Description BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to SLE, divided into 9 organ systems. For each organ system based on alphabetic score: A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. BILAG evaluated by scoring each of a list of signs and symptoms as: improving (1); same (2); worse (3); new (4); not present (0); not done (ND). Total BILAG score is sum of scores of 9 domains where A=12, B=8, C=1, D=0, and E=0. Total score ranges from 0 to 108 with a higher score indicating greater lupus activity. Time to first severe flare, where a severe flare is defined as at least one BILAG A (Severe disease activity) score in any organ system due to items that are new or worse, compared to the BILAG evaluation at the previous visit, during the 52-Week Treatment. It was measured using Kaplan-Meier (KM) estimates.
Time Frame Baseline up to Week 56
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set included all randomized participants who had received at least one dose of IMP (Evobrutinib or placebo) and have at least one Baseline and one post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 14 16 11 12
Median (Full Range)
Unit of Measure: Days
NA [1] 
(29.0 to 337.0)
NA [1] 
(29.0 to 367.0)
NA [1] 
(29.0 to 225.0)
NA [1] 
(28.0 to 162.0)
[1]
NA indicated that median was not reached as the number of participants with events were too low in respect to number of participants censored to estimate the value.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7034
Comments [Not Specified]
Method Cox proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.17
Confidence Interval (2-Sided) 95%
0.57 to 2.40
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5462
Comments [Not Specified]
Method Cox proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.69
Confidence Interval (2-Sided) 95%
0.31 to 1.52
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5462
Comments [Not Specified]
Method Cox proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.42 to 1.97
Estimation Comments [Not Specified]
31.Secondary Outcome
Title DBPC Period: Number of Participants With Response Based on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Week 52 in Serologically Active (SA) Subgroup
Hide Description SRI-4 response was defined as greater than or equal to (>=) 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score, no new British Isles Lupus Assessment Group (BILAG) A and no more than 1 new BILAG B domain score, no worsening (less than 10 percent increase) from baseline in Physician's Global Assessment of Disease Activity (PGA) and no treatment failure. SLEDAI-2K assessment consists of 24 items with total score of 0(no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to Systemic Lupus Erythematosus (SLE), divided into 9 organ systems. For each organ system A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. The PGA assess disease activity on a visual analogue scale =from 0(very well) to 100(very poor).
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set included all randomized participants who had received at least one dose of IMP (Evobrutinib or placebo) and have at least one Baseline and one post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI. Here, "Overall Number of Participants Analyzed" signifies those participants with positive anti-double-stranded deoxyribonucleic acid (antidsDNA) and/or low complement levels at screening (Serologically active subgroup).
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 59 65 60 63
Measure Type: Count of Participants
Unit of Measure: Participants
28
  47.5%
38
  58.5%
29
  48.3%
34
  54.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5462
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.52
Confidence Interval (2-Sided) 95%
0.74 to 3.15
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5462
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.49 to 2.13
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5462
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.35
Confidence Interval (2-Sided) 95%
0.65 to 2.81
Estimation Comments [Not Specified]
32.Secondary Outcome
Title DBPC Period: Number of Participants With Response Based on Systemic Lupus Erythematosus Responder Index 6 (SRI-6) at Week 52 in Serologically Active Subgroup
Hide Description SRI-6 response was defined as >= 6-point reduction in SLEDAI-2K total score, no new BILAG A and no more than 1 new BILAG B domain score and no worsening (less than 10 percent increase) from baseline in Physician's Global Assessment of Disease Activity (PGA) and treatment failure. SLEDAI-2K assessment consists of 24 items with total score of 0 (no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to SLE, divided into 9 organ systems. For each organ system :A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. The PGA assess disease activity on a visual analogue scale = from 0(very well) to 100(very poor).
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set included all randomized participants who had received at least one dose of IMP (Evobrutinib or placebo) and have at least one Baseline and one post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI. Here, "Overall Number of Participants Analyzed" signifies those participants with positive anti-double-stranded deoxyribonucleic acid (antidsDNA) and/or low complement levels at screening (Serologically active subgroup).
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 59 65 60 63
Measure Type: Count of Participants
Unit of Measure: Participants
17
  28.8%
25
  38.5%
23
  38.3%
23
  36.5%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2434
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.60
Confidence Interval (2-Sided) 95%
0.73 to 3.54
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2389
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.62
Confidence Interval (2-Sided) 95%
0.73 to 3.63
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1952
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.71
Confidence Interval (2-Sided) 95%
0.76 to 3.85
Estimation Comments [Not Specified]
33.Secondary Outcome
Title DBPC Period: Time to First British Isles Lupus Assessment Group (BILAG) A or 2B Moderate to Severe Flare
Hide Description BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to SLE, divided into 9 organ systems. For each organ system based on alphabetic score: A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. BILAG evaluated by scoring each of a list of signs and symptoms as: improving (1); same (2); worse (3); new (4); not present (0); not done (ND). Total BILAG score is sum of scores of 9 domains where A=12, B=8, C=1, D=0, and E=0. Total score ranges from 0 to 108 with a higher score indicating greater lupus activity. A Moderate to Severe (BILAG A or 2B) flare is defined as at least one BILAG A (severe disease activity) grade or two BILAG B (moderate disease activity) grade in any organ system due to items that are new or worse, compared to the BILAG evaluation at the previous visit, during the 52 week treatment. It was measured using Kaplan-Meier (KM) estimates.
Time Frame Baseline up to Week 56
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set included all randomized participants who had received at least one dose of IMP (Evobrutinib or placebo) and have at least one Baseline and one post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 18 27 19 19
Median (Full Range)
Unit of Measure: Days
NA [1] 
(29.0 to 337.0)
NA [1] 
(27.0 to 365.0)
NA [1] 
(29.0 to 308.0)
NA [1] 
(28.0 to 334.0)
[1]
NA indicated that median was not reached as the number of participants with events were too low in respect to number of participants censored to estimate the value.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0987
Comments [Not Specified]
Method Cox proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.59
Confidence Interval (2-Sided) 95%
0.87 to 2.89
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9201
Comments [Not Specified]
Method Cox proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.97
Confidence Interval (2-Sided) 95%
0.51 to 1.85
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5645
Comments [Not Specified]
Method Cox proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.15
Confidence Interval (2-Sided) 95%
0.60 to 2.20
Estimation Comments [Not Specified]
34.Secondary Outcome
Title DBPC Period: Number of Participants With British Isles Lupus Assessment Group (BILAG) 2004 Flare-Free Status During the 52-Week Treatment Period
Hide Description A participant has a flare-free status if no flare has been reported during the 52-week treatment period. Participants who discontinued treatment prior to Week 52, without having a flare are counted as not being flare free at Week 52. A flare was defined as either 1 or more new BILAG-2004 A (severe disease activity) or 2 or more new BILAG-2004 B (moderate disease activity) items compared to the previous visit. BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to SLE, divided into 9 organ systems. For each organ system based on alphabetic score: A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected.
Time Frame up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set included all randomized participants who had received at least one dose of IMP (Evobrutinib or placebo) and have at least one Baseline and one post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 114 115 116 114
Measure Type: Count of Participants
Unit of Measure: Participants
41
  36.0%
35
  30.4%
37
  31.9%
33
  28.9%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3743
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.44 to 1.37
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6445
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.50 to 1.54
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2634
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.72
Confidence Interval (2-Sided) 95%
0.41 to 1.28
Estimation Comments [Not Specified]
35.Secondary Outcome
Title DBPC Period: Annualized Flare Rate
Hide Description A flare was defined as either 1 or more new BILAG-2004 A (severe disease activity) or 2 or more new BILAG-2004 B (moderate disease activity) items compared to the previous visit. The occurrence of a new flare was checked for each available visit versus the previous available visit up to Week 52. If no new flares occurred, the number of flares was set to 0. Otherwise all flares were counted leading to the maximum number of flares of 13. The annualized flare rate was calculated as the number of flares divided by the flare exposure time in days multiplied with 365.25 (1 year). The flare exposure time is the time up to Week 52 (date of BILAG-2004 assessment at Week 52) or up to the date of last available BILAG 2004 assessment.
Time Frame Baseline up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set included all randomized participants who had received at least one dose of IMP (Evobrutinib or placebo) and have at least one Baseline and one post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 114 115 116 114
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Annualized flare rate ratio
0.15
(0.06 to 0.39)
0.23
(0.09 to 0.59)
0.13
(0.05 to 0.33)
0.19
(0.07 to 0.51)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2989
Comments Nominal p-value
Method Negative binomial regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 1.59
Confidence Interval (2-Sided) 95%
0.66 to 3.81
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7325
Comments Nominal p-value
Method Negative binomial regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.33 to 2.19
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5910
Comments Nominal p-value
Method Negative binomial regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 1.29
Confidence Interval (2-Sided) 95%
0.51 to 3.22
Estimation Comments [Not Specified]
36.Secondary Outcome
Title DBPC Period: Number of Participants With Low Disease Activity Status, Defined by Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) Score of Less Than or Equal (<= ) 2 at Week 52
Hide Description Low disease activity is defined as SLEDAI-2K score <=2. SLEDAI-2K is an activity index that measures disease activity and records feature of active lupus as present or not present. SLEDAI-2K uses a weighted checklist to assign a numerical score based on the presence or absence of 24 symptoms at the time of assessment or during the previous 30 days. Each symptom present is assigned between 1 and 8 points based on its usual clinical importance, yielding a total score that ranges from 0 points (no symptoms) to 105 points (presence of all defined symptoms).
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set included all randomized participants who had received at least one dose of IMP (Evobrutinib or placebo) and have at least one Baseline and one post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 114 115 116 114
Measure Type: Count of Participants
Unit of Measure: Participants
26
  22.8%
32
  27.8%
39
  33.6%
28
  24.6%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3635
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.33
Confidence Interval (2-Sided) 95%
0.72 to 2.47
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0329
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.94
Confidence Interval (2-Sided) 95%
1.06 to 3.56
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7619
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.10
Confidence Interval (2-Sided) 95%
0.59 to 2.07
Estimation Comments [Not Specified]
37.Secondary Outcome
Title DBPC Period: Number of Participants With Low Disease Activity Status, Defined by Clinical Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) Score of Less Than or Equal (<= ) 2 at Week 52
Hide Description Low disease activity is defined as SLEDAI-2K score <=2. SLEDAI-2K is an activity index that measures disease activity and records feature of active lupus as present or not present. SLEDAI-2K uses a weighted checklist to assign a numerical score based on the presence or absence of 24 symptoms at the time of assessment or during the previous 30 days. Each symptom present is assigned between 1 and 8 points based on its usual clinical importance, yielding a total score that ranges from 0 points (no symptoms) to 105 points (presence of all defined symptoms). Clinical SLEDAI-2K score is equal to the SLEDAI-2K score from electronic case report form (eCRF) excluding the components 'Increased Deoxyribonucleic acid (DNA) Binding' and 'Low Complement'.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set included all randomized participants who had received at least one dose of IMP (Evobrutinib or placebo) and have at least one Baseline and one post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 114 115 116 114
Measure Type: Count of Participants
Unit of Measure: Participants
42
  36.8%
50
  43.5%
52
  44.8%
41
  36.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2642
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.36
Confidence Interval (2-Sided) 95%
0.79 to 2.35
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1489
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.49
Confidence Interval (2-Sided) 95%
0.87 to 2.57
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9285
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.97
Confidence Interval (2-Sided) 95%
0.56 to 1.70
Estimation Comments [Not Specified]
38.Secondary Outcome
Title DBPC Period: Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) Score at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Hide Description SLEDAI-2K is an activity index that measures disease activity and records feature of active lupus as present or not present. SLEDAI-2K uses a weighted checklist to assign a numerical score based on the presence or absence of 24 symptoms at the time of assessment or during the previous 30 days. Each symptom present is assigned between 1 and 8 points based on its usual clinical importance, yielding a total score that ranges from 0 points (no symptoms) to 105 points (presence of all defined symptoms).
Time Frame Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set included all randomized participants who had received at least 1 dose of IMP (Evobrutinib or placebo) and have at least 1 Baseline and 1 post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 111 115 115 113
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Week 4 Number Analyzed 111 participants 115 participants 115 participants 113 participants
-1  (1.9) -1  (2.1) 0  (1.9) -1  (2.2)
Week 8 Number Analyzed 111 participants 111 participants 112 participants 109 participants
-2  (3.1) -2  (3.2) -2  (3.0) -2  (3.2)
Week 12 Number Analyzed 109 participants 106 participants 109 participants 104 participants
-3  (3.8) -3  (3.3) -3  (3.2) -3  (3.4)
Week 16 Number Analyzed 104 participants 102 participants 107 participants 98 participants
-4  (3.7) -3  (3.4) -3  (3.4) -3  (3.6)
Week 20 Number Analyzed 101 participants 99 participants 103 participants 96 participants
-4  (4.1) -4  (3.8) -4  (3.4) -4  (3.4)
Week 24 Number Analyzed 98 participants 95 participants 101 participants 94 participants
-4  (4.0) -4  (3.7) -4  (3.6) -3  (3.4)
Week 28 Number Analyzed 93 participants 94 participants 99 participants 89 participants
-4  (3.9) -4  (3.6) -4  (3.5) -4  (3.5)
Week 32 Number Analyzed 92 participants 91 participants 97 participants 88 participants
-4  (4.0) -4  (3.5) -4  (3.7) -4  (3.4)
Week 36 Number Analyzed 91 participants 90 participants 95 participants 113 participants
-4  (4.3) -5  (3.5) -5  (3.6) -4  (3.5)
Week 40 Number Analyzed 90 participants 90 participants 95 participants 87 participants
-5  (4.1) -5  (3.6) -5  (3.8) -4  (3.3)
Week 44 Number Analyzed 89 participants 90 participants 92 participants 86 participants
-4  (4.0) -5  (3.7) -5  (3.9) -4  (3.5)
Week 48 Number Analyzed 89 participants 90 participants 92 participants 85 participants
-4  (4.1) -5  (3.7) -5  (3.8) -5  (3.3)
Week 52 Number Analyzed 85 participants 89 participants 91 participants 84 participants
-5  (4.0) -5  (3.7) -5  (3.7) -5  (3.9)
39.Secondary Outcome
Title DBPC Period: Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) Score at Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Hide Description CLASI is an validated measurement instrument for lupus erythematosus developed for use in clinical studies that consists of separate scores for the activity of the disease (CLASI-A). The CLASI activity score is calculated on the basis of erythema, scale/hyperkeratosis, mucous membrane involvement, acute hair loss and non-scarring alopecia. The CLASI activity score ranges from 0-70, with higher scores indicating more severe skin disease. Severity categories based on the CLASI activity score are as follows: mild (0-9), moderate (10-20), and severe (21-70).
Time Frame Baseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set included all randomized participants who had received at least 1 dose of IMP (Evobrutinib or placebo) and have at least 1 Baseline and 1 post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 111 113 115 113
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Week 2 Number Analyzed 110 participants 113 participants 113 participants 109 participants
-1  (1.9) -1  (1.6) 0  (1.6) 0  (1.2)
Week 4 Number Analyzed 111 participants 113 participants 115 participants 113 participants
-1  (1.9) -1  (3.5) -1  (2.4) -1  (2.2)
Week 8 Number Analyzed 110 participants 109 participants 110 participants 107 participants
-2  (2.8) -1  (4.2) -1  (2.3) -1  (2.5)
Week 12 Number Analyzed 107 participants 104 participants 107 participants 101 participants
-2  (2.8) -2  (3.3) -2  (3.2) -2  (2.7)
Week 16 Number Analyzed 104 participants 102 participants 107 participants 98 participants
-2  (3.1) -2  (3.9) -2  (3.3) -2  (2.7)
Week 20 Number Analyzed 99 participants 96 participants 102 participants 95 participants
-3  (3.6) -3  (4.4) -3  (3.4) -2  (2.9)
Week 24 Number Analyzed 97 participants 95 participants 100 participants 92 participants
-3  (3.5) -3  (4.7) -3  (3.6) -2  (2.7)
Week 28 Number Analyzed 92 participants 91 participants 96 participants 89 participants
-3  (3.7) -3  (4.6) -3  (3.4) -2  (2.7)
Week 32 Number Analyzed 91 participants 91 participants 96 participants 87 participants
-3  (3.5) -3  (4.4) -3  (3.6) -3  (3.2)
Week 36 Number Analyzed 90 participants 89 participants 95 participants 86 participants
-3  (3.5) -3  (4.6) -3  (3.4) -3  (3.6)
Week 40 Number Analyzed 90 participants 90 participants 92 participants 85 participants
-3  (3.0) -3  (4.6) -3  (3.6) -3  (3.8)
Week 44 Number Analyzed 89 participants 90 participants 92 participants 85 participants
-3  (3.2) -3  (4.5) -3  (3.7) -3  (3.8)
Week 48 Number Analyzed 88 participants 89 participants 91 participants 83 participants
-3  (3.2) -3  (4.7) -3  (3.7) -3  (3.9)
Week 52 Number Analyzed 84 participants 86 participants 89 participants 84 participants
-3  (3.6) -4  (4.8) -3  (3.7) -3  (4.0)
40.Secondary Outcome
Title DBPC Period: Number of Participants With Response Based on BILAG-Based Composite Lupus Assessment (BICLA) at Week 52
Hide Description BICLA response defined as participants meeting following criteria: [1] At least one gradation of improvement in baseline BILAG scores in all body systems with moderate or severe disease activity at entry (example: all A (severe disease) scores falling to B (moderate), C (mild), or D (no activity) and all B scores falling to C or D; [2] No new BILAG A or more than one new BILAG B scores; [3] No worsening of total SLEDAI-2K score from baseline; [4] No significant deterioration (=<10%) in physician's global assessment and [5] No treatment failure (initiation of non-protocol treatment).
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set included all randomized participants who had received at least one dose of IMP (Evobrutinib or placebo) and have at least one Baseline and one post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI. Here, "Overall Number of Participants Analyzed" signifies those participants who have at least 1 BILAG A or 2 BILAG B grades at Baseline (BICLA Subpopulation).
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 76 73 76 70
Measure Type: Count of Participants
Unit of Measure: Participants
30
  39.5%
29
  39.7%
33
  43.4%
24
  34.3%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9061
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.96
Confidence Interval (2-Sided) 95%
0.49 to 1.88
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6053
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.19
Confidence Interval (2-Sided) 95%
0.61 to 2.31
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5200
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.80
Confidence Interval (2-Sided) 95%
0.40 to 1.59
Estimation Comments [Not Specified]
41.Secondary Outcome
Title DBPC Period: Change From Baseline in British Isles Lupus Assessment Group (BILAG)-2004 Score at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Hide Description BILAG 2004 disease activity Index: assessing clinical signs, symptoms, or laboratory parameters related to SLE, divided into 9 organ systems. For each organ system based on alphabetic score: A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. BILAG evaluated by scoring each of a list of signs and symptoms as: improving (1); same (2); worse (3); new (4); not present (0); not done (ND). Total BILAG score is sum of scores of 9 domains where A=12, B=8, C=1, D=0, and E=0. Total score ranges from 0 to 108 with a higher score indicating greater lupus activity.
Time Frame Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set included all randomized participants who had received at least 1 dose of IMP (Evobrutinib or placebo) and have at least 1 Baseline and 1 post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 110 111 109 109
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Week 4 Number Analyzed 108 participants 108 participants 108 participants 105 participants
-4  (5.8) -4  (6.1) -3  (6.3) -4  (6.2)
Week 8 Number Analyzed 110 participants 111 participants 109 participants 109 participants
-6  (6.0) -5  (7.0) -6  (6.3) -6  (6.1)
Week 12 Number Analyzed 109 participants 106 participants 107 participants 104 participants
-7  (6.7) -7  (6.8) -6  (7.0) -6  (6.2)
Week 16 Number Analyzed 104 participants 102 participants 105 participants 98 participants
-7  (6.9) -7  (7.6) -6  (6.8) -6  (5.9)
Week 20 Number Analyzed 101 participants 99 participants 102 participants 96 participants
-7  (6.8) -7  (7.3) -7  (7.6) -6  (6.2)
Week 24 Number Analyzed 97 participants 95 participants 100 participants 94 participants
-8  (6.9) -7  (6.5) -8  (7.7) -6  (6.3)
Week 28 Number Analyzed 93 participants 94 participants 98 participants 89 participants
-8  (6.7) -8  (6.9) -8  (7.4) -7  (6.2)
Week 32 Number Analyzed 92 participants 91 participants 96 participants 89 participants
-9  (6.7) -8  (7.3) -8  (7.9) -7  (6.0)
Week 36 Number Analyzed 91 participants 90 participants 95 participants 88 participants
-8  (7.1) -8  (7.2) -8  (7.4) -7  (6.7)
Week 40 Number Analyzed 88 participants 90 participants 95 participants 87 participants
-9  (6.8) -8  (6.7) -9  (7.7) -7  (6.6)
Week 44 Number Analyzed 88 participants 90 participants 92 participants 85 participants
-9  (7.2) -9  (7.2) -9  (7.9) -7  (6.7)
Week 48 Number Analyzed 89 participants 90 participants 92 participants 85 participants
-8  (7.1) -8  (7.2) -9  (7.6) -7  (6.5)
Week 52 Number Analyzed 85 participants 89 participants 91 participants 84 participants
-8  (7.0) -9  (6.8) -9  (7.8) -7  (6.7)
42.Secondary Outcome
Title DBPC Period: Change From Baseline in Physician's Global Assessment (PGA) Score at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Hide Description The Physician's Global Assessment of Disease Activity was recorded using the 100 millimeter horizontal Visual Analog Scale (VAS). Physician rated participant's disease activity on a scale ranged from 0-100 millimeter (mm), where 0 indicated no disease activity and 100 represented maximum disease activity.
Time Frame Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set included all randomized participants who had received at least 1 dose of IMP (Evobrutinib or placebo) and have at least 1 Baseline and 1 post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 111 115 115 113
Mean (Standard Deviation)
Unit of Measure: Millimeter
Week 4 Number Analyzed 111 participants 115 participants 115 participants 113 participants
-8  (11.7) -8  (14.1) -9  (13.4) -9  (12.1)
Week 8 Number Analyzed 110 participants 109 participants 111 participants 107 participants
-13  (16.2) -14  (16.5) -13  (15.5) -14  (15.9)
Week 12 Number Analyzed 107 participants 104 participants 107 participants 101 participants
-18  (17.4) -18  (18.8) -19  (18.3) -18  (16.9)
Week 16 Number Analyzed 104 participants 102 participants 105 participants 98 participants
-21  (17.6) -20  (19.7) -21  (18.7) -19  (18.0)
Week 20 Number Analyzed 99 participants 96 participants 102 participants 95 participants
-23  (19.2) -21  (19.5) -24  (17.9) -20  (18.6)
Week 24 Number Analyzed 97 participants 95 participants 100 participants 92 participants
-24  (17.8) -24  (20.0) -25  (19.2) -21  (18.0)
Week 28 Number Analyzed 92 participants 91 participants 96 participants 89 participants
-26  (17.6) -26  (20.3) -26  (18.6) -24  (17.8)
Week 32 Number Analyzed 91 participants 91 participants 96 participants 87 participants
-26  (17.8) -26  (20.8) -26  (19.0) -26  (17.5)
Week 36 Number Analyzed 90 participants 89 participants 95 participants 86 participants
-26  (17.9) -26  (20.9) -29  (18.3) -26  (18.3)
Week 40 Number Analyzed 90 participants 90 participants 91 participants 85 participants
-27  (16.9) -27  (19.1) -30  (19.7) -25  (18.1)
Week 44 Number Analyzed 89 participants 90 participants 92 participants 85 participants
-28  (16.6) -28  (20.1) -30  (20.7) -26  (16.6)
Week 48 Number Analyzed 88 participants 89 participants 91 participants 83 participants
-29  (16.5) -29  (19.5) -32  (18.8) -28  (18.3)
Week 52 Number Analyzed 84 participants 86 participants 89 participants 84 participants
-29  (16.2) -31  (20.7) -33  (19.2) -27  (18.1)
43.Secondary Outcome
Title DBPC Period: Change From Baseline in Study 36-Item Short Form Health Survey Version 2 (SF-36v2) Physical Component Summary Score and Mental Component Summary Scores at Week 4, 8, 12, 16, 24, 32, 40 and 52
Hide Description The 36-Item Short-Form Health Survey (SF-36) was a standardized survey evaluating 8 aspects of functional health and well-being. These eight subscales were summarized as relating to either physical health or mental health. Physical component summary (PCS) was based primarily on physical functioning, role-physical, bodily pain, and general health scales and mental component summary (MCS) encompasses vitality, social functioning, role-emotional, and mental health scales. Score from mental health, role emotional, social functioning, and vitality domains were averaged to calculate MCS. Total score range for MCS was 0 - 100 (100 = highest level of mental functioning). Score from physical function, role physical, bodily pain, and general health domains were averaged to calculate PCS. Total score range for PCS was 0-100 (100 = highest level of physical functioning).
Time Frame Baseline, Week 4, 8, 12, 16, 24, 32, 40 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Quality of Life analysis set included all randomized participants who had received at least 1 dose of IMP (Evobrutinib or placebo) and had at least 1 Baseline and 1 post baseline QoL assessment. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 110 114 112 113
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Physical Component Summary Score at Week 4 Number Analyzed 110 participants 114 participants 112 participants 113 participants
1.2  (5.42) 2.5  (7.40) 3.5  (6.01) 2.2  (5.86)
Physical Component Summary Score at Week 8 Number Analyzed 107 participants 108 participants 109 participants 106 participants
1.8  (6.35) 3.5  (7.69) 3.0  (6.61) 2.2  (6.63)
Physical Component Summary Score at Week 12 Number Analyzed 106 participants 102 participants 103 participants 101 participants
2.4  (6.44) 3.7  (7.71) 4.2  (6.68) 3.0  (6.99)
Physical Component Summary Score at Week 16 Number Analyzed 101 participants 101 participants 105 participants 96 participants
3.3  (7.04) 4.0  (7.56) 4.4  (5.81) 3.4  (6.77)
Physical Component Summary Score at Week 24 Number Analyzed 96 participants 95 participants 99 participants 95 participants
3.4  (7.08) 4.6  (7.57) 5.4  (7.63) 2.8  (7.15)
Physical Component Summary Score at Week 32 Number Analyzed 90 participants 91 participants 93 participants 88 participants
3.5  (8.03) 3.8  (7.36) 5.4  (7.24) 3.8  (6.89)
Physical Component Summary Score at Week 40 Number Analyzed 88 participants 89 participants 91 participants 86 participants
4.2  (7.11) 4.6  (7.97) 5.7  (7.76) 4.1  (8.59)
Physical Component Summary Score at Week 52 Number Analyzed 86 participants 84 participants 87 participants 82 participants
3.7  (8.32) 5.4  (7.05) 6.5  (8.58) 4.8  (7.76)
Mental Component Summary Score at Week 4 Number Analyzed 110 participants 114 participants 112 participants 113 participants
3.9  (9.38) 1.7  (9.25) 1.9  (7.93) 2.4  (7.68)
Mental Component Summary Score at Week 8 Number Analyzed 107 participants 108 participants 109 participants 106 participants
2.5  (8.59) 2.2  (8.81) 1.6  (8.48) 3.6  (9.04)
Mental Component Summary Score at Week 12 Number Analyzed 106 participants 102 participants 103 participants 101 participants
3.1  (10.07) 3.1  (8.45) 0.8  (10.39) 2.9  (8.89)
Mental Component Summary Score at Week 16 Number Analyzed 101 participants 101 participants 105 participants 96 participants
3.6  (9.84) 2.5  (8.39) 2.8  (9.39) 2.9  (9.13)
Mental Component Summary Score at Week 24 Number Analyzed 96 participants 95 participants 99 participants 95 participants
2.9  (9.75) 2.4  (8.41) 3.4  (9.68) 2.7  (8.87)
Mental Component Summary Score at Week 32 Number Analyzed 90 participants 91 participants 93 participants 88 participants
3.5  (8.55) 1.8  (9.51) 2.8  (9.71) 4.3  (9.03)
Mental Component Summary Score at Week 40 Number Analyzed 88 participants 89 participants 91 participants 86 participants
4.5  (8.81) 1.5  (10.55) 3.2  (9.81) 4.0  (9.85)
Mental Component Summary Score at Week 52 Number Analyzed 86 participants 84 participants 87 participants 82 participants
3.8  (9.45) 1.7  (9.91) 3.9  (11.21) 4.6  (9.80)
44.Secondary Outcome
Title DBPC Period: Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire at Week 4, 8, 12, 16, 24, 32, 40 and 52
Hide Description The EQ-5D-5L questionnaire is a generic measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L profile defines health in terms of mobility, self-care, usual activities, pain or discomfort, and anxiety or depression. Each dimension has five levels: 1: no problems, 2: slight problems, 3: moderate problems, 4: severe problems, and 5: extreme problems. Responses were used to generate a weighted summary index (EQ-5D index), which ranges from 0 (dead) to 1.00 (perfect health). A higher score indicates better health and positive changes from baseline indicate improvement of health.
Time Frame Baseline, Week 4, 8, 12, 16, 24, 32, 40, and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Quality of Life analysis set included all randomized participants who had received at least 1 dose of IMP (Evobrutinib or placebo) and had at least 1 Baseline and 1 post baseline QoL assessment. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 110 114 112 113
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Week 4 Number Analyzed 110 participants 114 participants 112 participants 113 participants
0.036  (0.1626) 0.045  (0.1931) 0.036  (0.1618) 0.038  (0.1908)
Week 8 Number Analyzed 107 participants 108 participants 109 participants 106 participants
0.034  (0.2164) 0.064  (0.2505) 0.046  (0.1842) 0.061  (0.1603)
Week 12 Number Analyzed 106 participants 102 participants 103 participants 101 participants
0.061  (0.2014) 0.070  (0.2189) 0.055  (0.1912) 0.065  (0.1732)
Week 16 Number Analyzed 101 participants 101 participants 105 participants 96 participants
0.083  (0.1818) 0.072  (0.2252) 0.067  (0.2287) 0.056  (0.1738)
Week 24 Number Analyzed 96 participants 95 participants 99 participants 95 participants
0.080  (0.1901) 0.067  (0.2271) 0.086  (0.2110) 0.055  (0.1817)
Week 32 Number Analyzed 90 participants 91 participants 93 participants 88 participants
0.083  (0.1758) 0.067  (0.2262) 0.075  (0.2009) 0.071  (0.1941)
Week 40 Number Analyzed 88 participants 89 participants 91 participants 86 participants
0.093  (0.1521) 0.061  (0.1850) 0.090  (0.1853) 0.084  (0.2172)
Week 52 Number Analyzed 86 participants 84 participants 87 participants 82 participants
0.096  (0.2092) 0.078  (0.2197) 0.102  (0.2224) 0.096  (0.2051)
45.Secondary Outcome
Title DBPC Period: Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Visual Analog Scale (VAS) at Week 4, 8, 12, 16, 24, 32, 40 and 52
Hide Description The EQ-5D-5L questionnaire is a generic measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L profile defines health in terms of mobility, self-care, usual activities, pain or discomfort, and anxiety or depression. Each dimension has five levels: 1: no problems, 2: slight problems, 3: moderate problems, 4: severe problems, and 5: extreme problems. The responses were used to derive overall score using a visual analog scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 was the worst health you can imagine and 100 was the best health you can imagine.
Time Frame Baseline, Week 4, 8, 12, 16, 24, 32, 40, and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Quality of Life analysis set included all randomized participants who had received at least 1 dose of IMP (Evobrutinib or placebo) and had at least 1 Baseline and 1 post baseline QoL assessment. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 110 114 112 113
Mean (Standard Deviation)
Unit of Measure: Millimeter
Week 4 Number Analyzed 110 participants 114 participants 112 participants 113 participants
3  (16.8) 2  (19.0) 4  (17.6) 4  (18.2)
Week 8 Number Analyzed 107 participants 108 participants 109 participants 106 participants
3  (18.8) 6  (20.0) 4  (14.5) 6  (16.5)
Week 12 Number Analyzed 106 participants 102 participants 103 participants 101 participants
5  (19.7) 6  (17.4) 5  (17.2) 4  (16.8)
Week 16 Number Analyzed 101 participants 101 participants 105 participants 96 participants
7  (19.3) 5  (18.1) 6  (18.5) 4  (15.5)
Week 24 Number Analyzed 96 participants 95 participants 99 participants 95 participants
7  (18.7) 5  (18.4) 9  (20.4) 4  (17.3)
Week 32 Number Analyzed 90 participants 91 participants 93 participants 88 participants
8  (17.2) 4  (21.1) 7  (17.8) 7  (16.6)
Week 40 Number Analyzed 88 participants 89 participants 91 participants 86 participants
8  (18.1) 6  (18.1) 10  (19.5) 8  (18.9)
Week 52 Number Analyzed 86 participants 84 participants 87 participants 82 participants
8  (19.9) 8  (18.6) 10  (21.3) 10  (18.9)
46.Secondary Outcome
Title DBPC Period: Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score at Week 4, 8, 12, 16, 24, 32, 40 and 52
Hide Description The Lupus QoL assessment is a 34 item questionnaire across 8 domains that is designed to find out how systemic lupus erythematosus (SLE) affects a participant's life. Domains include physical health, pain, planning, intimate relationships, burden to others, emotional health, body image, and fatigue. Participants indicate their responses on a 5-point Likert response format, where 4=never, 3=occasionally, 2= a good bit of the time, 1=most of the time, and 0=worst of the time. Summary scores can be calculated for all 8 domains. A LupusQoL score for each domain was reported on a 0 to 100 scale, with greater values indicating better health related QoL.
Time Frame Baseline, Week 4, 8, 12, 16, 24, 32, 40, and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Quality of Life analysis set included all randomized participants who had received at least 1 dose of IMP (Evobrutinib or placebo) and had at least 1 Baseline and 1 post baseline QoL assessment. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.
Arm/Group Title DBPC Period: Placebo DBPC Period: M2951 25 mg QD DBPC Period: M2951 75 mg QD DBPC Period: M2951 50 mg BID
Hide Arm/Group Description:
Participants received placebo matched to M2951 orally for 52 weeks.
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.
Participants received 75 mg of M2951 orally QD for 52 weeks.
Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed 110 114 112 113
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Physical Health Week 4 Number Analyzed 110 participants 114 participants 112 participants 113 participants
1.9  (12.58) 4.7  (17.68) 4.0  (14.04) 3.5  (13.43)
Physical Health Week 8 Number Analyzed 107 participants 108 participants 109 participants 106 participants
2.8  (15.20) 6.3  (19.94) 3.8  (17.64) 4.6  (14.69)
Physical Health Week 12 Number Analyzed 106 participants 102 participants 103 participants 101 participants
4.8  (16.75) 6.7  (19.78) 5.6  (15.95) 5.7  (14.94)
Physical Health Week 16 Number Analyzed 101 participants 101 participants 105 participants 96 participants
6.6  (17.45) 6.1  (18.71) 7.4  (17.61) 6.2  (15.59)
Physical Health Week 24 Number Analyzed 96 participants 95 participants 99 participants 95 participants
6.9  (17.17) 7.2  (18.59) 8.4  (20.47) 6.1  (13.63)
Physical Health Week 32 Number Analyzed 90 participants 91 participants 93 participants 88 participants
5.7  (16.82) 6.7  (19.45) 9.4  (17.21) 7.0  (16.21)
Physical Health Week 40 Number Analyzed 88 participants 89 participants 91 participants 86 participants
7.6  (15.32) 8.2  (17.38) 9.6  (19.10) 7.1  (17.98)
Physical Health Week 52 Number Analyzed 86 participants 84 participants 87 participants 82 participants
7.1  (20.39) 9.0  (18.44) 11.6  (19.88) 7.9  (18.73)
Pain Week 4 Number Analyzed 110 participants 114 participants 112 participants 113 participants
3.6  (16.30) 6.7  (21.81) 9.0  (20.90) 5.7  (16.26)
Pain Week 8 Number Analyzed 107 participants 108 participants 109 participants 106 participants
4.8  (18.71) 9.9  (24.65) 7.3  (21.76) 6.7  (18.31)
Pain Week 12 Number Analyzed 106 participants 102 participants 103 participants 101 participants
7.5  (19.04) 8.8  (24.00) 9.8  (23.35) 5.5  (14.73)
Pain Week 16 Number Analyzed 101 participants 101 participants 105 participants 96 participants
9.4  (18.58) 8.3  (25.60) 10.5  (26.33) 6.9  (15.47)
Pain Week 24 Number Analyzed 96 participants 95 participants 99 participants 95 participants
9.4  (19.95) 9.3  (24.31) 13.0  (28.18) 6.2  (17.02)
Pain Week 32 Number Analyzed 90 participants 91 participants 93 participants 88 participants
6.7  (23.74) 9.2  (24.60) 12.8  (22.87) 8.7  (17.18)
Pain Week 40 Number Analyzed 88 participants 89 participants 91 participants 86 participants
11.0  (19.43) 10.9  (23.68) 15.3  (23.81) 9.6  (20.51)
Pain Week 52 Number Analyzed 86 participants 84 participants 87 participants 82 participants
10.2  (21.37) 12.9  (22.64) 14.9  (26.11) 9.6  (19.99)
Planning Week 4 Number Analyzed 110 participants 114 participants 112 participants 113 participants
4.8  (20.14) 4.9  (19.64) 5.4  (24.30) 4.6  (18.73)
Planning Week 8 Number Analyzed 107 participants 108 participants 109 participants 106 participants
5.5  (23.32) 8.4  (23.25) 5.8  (25.14) 3.9  (22.98)
Planning Week 12 Number Analyzed 106 participants 102 participants 103 participants 101 participants
7.8  (23.58) 5.8  (23.39) 6.8  (25.74) 5.1  (20.55)
Planning Week 16 Number Analyzed 101 participants 101 participants 105 participants 96 participants
8.3  (21.65) 5.3  (24.12) 6.5  (28.00) 6.3  (22.91)
Planning Week 24 Number Analyzed 96 participants 95 participants 99 participants 95 participants
7.9  (22.92) 8.1  (23.55) 11.5  (29.08) 5.6  (21.79)
Planning Week 32 Number Analyzed 90 participants 91 participants 93 participants 88 participants
6.5  (24.82) 7.6  (22.66) 9.9  (25.90) 6.9  (22.07)
Planning Week 40 Number Analyzed 88 participants 89 participants 91 participants 86 participants
9.0  (20.69) 7.8  (23.19) 11.6  (26.17) 8.0  (23.52)
Planning Week 52 Number Analyzed 86 participants 84 participants 87 participants 82 participants
9.9  (22.38) 7.0  (23.12) 9.9  (28.29) 10.5  (21.59)
Intimate Relationship Week 4 Number Analyzed 74 participants 88 participants 80 participants 71 participants
3.4  (26.11) 1.6  (28.29) 4.7  (24.06) 3.2  (24.06)
Intimate Relationship Week 8 Number Analyzed 70 participants 81 participants 75 participants 61 participants
8.2  (30.31) 4.2  (28.44) 9.7  (29.10) 3.7  (18.73)
Intimate Relationship Week 12 Number Analyzed 70 participants 75 participants 65 participants 59 participants
5.5  (27.31) 4.7  (25.65) 2.3  (30.37) 6.4  (21.32)
Intimate Relationship Week 16 Number Analyzed 60 participants 72 participants 69 participants 53 participants
8.8  (26.77) 1.6  (30.76) 3.8  (32.46) 4.2  (22.99)
Intimate Relationship Week 24 Number Analyzed 59 participants 70 participants 62 participants 47 participants
6.4  (30.12) 2.1  (28.79) 6.7  (30.76) 5.3  (26.29)
Intimate Relationship Week 32 Number Analyzed 54 participants 66 participants 54 participants 52 participants
2.5  (28.77) 1.3  (31.78) 6.5  (29.41) 1.4  (27.86)
Intimate Relationship Week 40 Number Analyzed 49 participants 61 participants 55 participants 48 participants
12.0  (27.59) 6.6  (27.91) 6.4  (32.53) 7.8  (22.72)
Intimate Relationship Week 52 Number Analyzed 51 participants 60 participants 49 participants 45 participants
7.4  (26.48) 4.4  (28.36) 8.4  (29.58) 8.9  (24.52)
Burden to Others Week 4 Number Analyzed 110 participants 114 participants 112 participants 113 participants
5.8  (23.83) 5.2  (22.84) 6.8  (24.85) 2.2  (24.24)
Burden to Others Week 8 Number Analyzed 107 participants 108 participants 109 participants 106 participants
5.6  (22.42) 9.3  (27.17) 5.7  (25.80) 8.0  (25.79)
Burden to Others Week 12 Number Analyzed 106 participants 102 participants 103 participants 101 participants
8.6  (25.86) 6.7  (28.00) 7.4  (25.93) 7.3  (24.74)
Burden to Others Week 16 Number Analyzed 101 participants 101 participants 105 participants 96 participants