A Phase II Study of M2951 in SLE

• Sponsor: EMD Serono Research & Development Institute, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02975336
• Collaborator: Merck KGaA, Darmstadt, Germany (Industry)
• Enrollment: 469
• Locations: 157
• Arms: 8
• Actual Duration (Months): 38.6
• Patients Per Site: 3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

M2951 is an investigational drug under evaluation for treatment of autoimmune and inflammatory disorders. The purpose of the study was to assess the Safety and Efficacy of M2951 in participants with Systemic Lupus Erythematosus (SLE).

Condition or Disease	Intervention/Treatment	Phase
Systemic Lupus Erythematosus	Drug: Placebo; Drug: M2951; Drug: M2951; Drug: M2951; Drug: M2951	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 469 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase II, Randomized, Double-Blind, Placebo-Controlled Dose-Ranging Study To Evaluate the Safety and Efficacy of M2951 in Subjects With SLE
• Actual Study Start Date: Jan 4, 2017
• Actual Primary Completion Date: Nov 27, 2019
• Actual Study Completion Date: Mar 23, 2020

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Double-Blind Placebo-Controlled (DBPC) Period: Placebo	Drug: Placebo; Participants received placebo matched to M2951 orally for 52 weeks.
Experimental: DBPC Period: M2951 25 mg QD	Drug: M2951; Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.; Other Names: Evobrutinib
Experimental: DBPC Period: M2951 75 mg QD	Drug: M2951; Participants received 75 mg of M2951 orally QD for 52 weeks.; Other Names: Evobrutinib
Experimental: DBPC Period: M2951 50 mg BID	Drug: M2951; Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.; Other Names: Evobrutinib
Experimental: Long-Term Extension (LTE) Period: Placebo/ M2951 50 mg BID	Drug: M2951; Participants who had received Placebo or M2951 (25 mg QD, 75 mg QD or 50 mg BID) during DBPC period were switched to receive 50 mg M2951 orally BID in LTE period for 104 weeks.; Other Names: Evobrutinib
Experimental: LTE Period: M2951 25 mg QD/ M2951 50 mg BID	Drug: M2951; Participants who had received Placebo or M2951 (25 mg QD, 75 mg QD or 50 mg BID) during DBPC period were switched to receive 50 mg M2951 orally BID in LTE period for 104 weeks.; Other Names: Evobrutinib
Experimental: LTE Period: M2951 75 mg QD/ M2951 50 mg BID	Drug: M2951; Participants who had received Placebo or M2951 (25 mg QD, 75 mg QD or 50 mg BID) during DBPC period were switched to receive 50 mg M2951 orally BID in LTE period for 104 weeks.; Other Names: Evobrutinib
Experimental: LTE Period: M2951 50 mg BID/ M2951 50 mg BID	Drug: M2951; Participants who had received Placebo or M2951 (25 mg QD, 75 mg QD or 50 mg BID) during DBPC period were switched to receive 50 mg M2951 orally BID in LTE period for 104 weeks.; Other Names: Evobrutinib

Outcome Measures

Primary Outcome Measures

1. DBPC Period: Number of Participants With Response Based on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Week 52 [Week 52]

   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).

2. DBPC Period: Number of Participants With Response Based on Systemic Lupus Erythematosus Responder Index 6 (SRI-6) at Week 52 [Week 52]

   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).

3. 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) [Baseline up to Week 56]

   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.

4. 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) [Baseline up to Week 56]

   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.

5. DBPC Period: Number of Participants With Clinically Significant Change From Baseline in Vital Signs [Baseline up to Week 56]

   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.

6. DBPC Period: Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings [Baseline up to Week 56]

   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.

7. DBPC Period: Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters [Baseline up to Week 56]

   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.

8. DBPC Period: Mean Absolute Value of Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2 [Week 2]

   Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 2.

9. DBPC Period: Mean Absolute Value of Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 4 [Week 4]

   Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 4.

10. DBPC Period: Mean Absolute Value of Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 12 [Week 12]

    Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 12.

11. DBPC Period: Mean Absolute Value of Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 24 [Week 24]

    Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 24.

12. DBPC Period: Mean Absolute Value of Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 36 [Week 36]

    Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 36.

13. DBPC Period: Mean Absolute Value of Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 52 [Week 52]

    Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 52

14. DBPC Period: Mean Absolute Value of Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 56 [Week 56]

    Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 56

15. DBPC Period: Mean Absolute Total B Cell Count at Week 4 [Week 4]

    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.

16. DBPC Period: Mean Absolute Total B Cell Count at Week 24 [Week 24]

    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.

17. DBPC Period: Mean Absolute Total B Cell Count at Week 52 [Week 52]

    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.

18. DBPC Period: Mean Absolute Total B Cell Count at Week 56 [Week 56]

    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.

19. DBPC Period: Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2 [Baseline and Week 2]

    Change from baseline in the serum levels of IgG, IgA, IgM were assessed.

20. DBPC Period: Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 4 [Baseline and Week 4]

    Change from baseline in the serum levels of IgG, IgA, IgM were assessed.

21. DBPC Period: Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 12 [Baseline and Week 12]

    Change from baseline in the serum levels of IgG, IgA, IgM were assessed.

22. DBPC Period: Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 24 [Baseline and Week 24]

    Change from baseline in the serum levels of IgG, IgA, IgM were assessed.

23. DBPC Period: Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 36 [Baseline and Week 36]

    Change from baseline in the serum levels of IgG, IgA, IgM were assessed.

24. DBPC Period: Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 52 [Baseline and Week 52]

    Change from baseline in the serum levels of IgG, IgA, IgM were assessed.

25. DBPC Period: Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 56 [Baseline and Week 56]

    Change from baseline in the serum levels of IgG, IgA, IgM were assessed.

26. DBPC Period: Change From Baseline in Total B Cell Count at Week 4 [Baseline and Week 4]

    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.

27. DBPC Period: Change From Baseline in Total B Cell Count at Week 24 [Baseline and Week 24]

    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.

28. DBPC Period: Change From Baseline in Total B Cell Count at Week 52 [Baseline and Week 52]

    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.

29. DBPC Period: Change From Baseline in Total B Cell Count at Week 56 [Baseline and Week 56]

    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.

Secondary Outcome Measures

1. DBPC Period: Time to First Severe British Isles Lupus Assessment Group (BILAG) A Flare [Baseline up to Week 56]

   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.

2. 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 [Week 52]

   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).

3. DBPC Period: Number of Participants With Response Based on Systemic Lupus Erythematosus Responder Index 6 (SRI-6) at Week 52 in Serologically Active Subgroup [Week 52]

   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).

4. DBPC Period: Time to First British Isles Lupus Assessment Group (BILAG) A or 2B Moderate to Severe Flare [Baseline up to Week 56]

   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.

5. DBPC Period: Number of Participants With British Isles Lupus Assessment Group (BILAG) 2004 Flare-Free Status During the 52-Week Treatment Period [up to Week 52]

   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.

6. DBPC Period: Annualized Flare Rate [Baseline up to 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. 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.

7. 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 [Week 52]

   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).

8. 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 [Week 52]

   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'.

9. 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 [Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52]

   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).

10. 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 [Baseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52]

    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).

11. DBPC Period: Number of Participants With Response Based on BILAG-Based Composite Lupus Assessment (BICLA) at Week 52 [Week 52]

    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).

12. 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 [Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52]

    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.

13. 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 [Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52]

    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.

14. 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 [Baseline, Week 4, 8, 12, 16, 24, 32, 40 and 52]

    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).

15. 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 [Baseline, Week 4, 8, 12, 16, 24, 32, 40, and 52]

    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.

16. 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 [Baseline, Week 4, 8, 12, 16, 24, 32, 40, and 52]

    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.

17. DBPC Period: Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score at Week 4, 8, 12, 16, 24, 32, 40 and 52 [Baseline, Week 4, 8, 12, 16, 24, 32, 40, and 52]

    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.

18. DBPC Period: Number of Participants With Patient Global Impression of Change (PGIC) Scale Score of Any Improvement, no Change and Any Worsening [Week 4, 8, 12, 16, 24, 32, 40, and 52]

    The PGIC is a self-rated scale that asks the participant to describe the change in activity limitations, symptoms, emotions, and overall quality of life (QoL) related to the participants painful condition on the following scale: 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse) and 7 (very much worse). Number of participants in the PGIC categories of any improvement (that is PGIC scale score 1, 2 or 3), no change (that is PGIC scale score 4) and any worsening (that is PGIC scale score 5, 6 or 7) are reported.

19. DBPC Period: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 4, 8, 12, 16, 24, 32, 40 and 52 [Baseline, Week 4, 8, 12, 16, 24, 32, 40, and 52]

    The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assess self reported fatigue and its impact upon daily activities and function. It uses a 5-point Likert-type scale (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; 4 = very much). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse possible score) to 52 (best score). A higher score reflected an improvement in the participant's health status.

20. DBPC Period: Number of Participants With Change From Baseline in Prednisone Equivalent Corticosteroid (CS) Dose by >=25% to a Dose of <=7.5 Milligram Per Day (mg/Day), With no BILAG A or 2B Flare in Disease Activity at Week 52 [Baseline and Week 52]

    BILAG A or 2B flare is defined as at least one BILAG A grade or two BILAG B 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 period. BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to systemic lupus erythematosus (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.

21. DBPC Period: Change From Baseline to Week 52 in Prednisone Equivalent Corticosteroid (CS) Daily Dose at at Week 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 [Baseline, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52]

    Change From Baseline in Prednisone-equivalent CS Daily Dose at Week 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 were reported.

22. DBPC Period: Number of Participants With Reduction From Baseline in Prednisone Equivalent Corticosteroid (CS) Daily Dose by > 0 to 25%, >25% to 50%, >50% to 100% or an Increase at Week 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 [Baseline, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52]

    Number of Participants With Reduction From Baseline in Prednisone-equivalent Corticosteroid (CS) Daily Dose by > 0 to 25%, >25% to 50%, >50% to 100% or an Increase at Week 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 were reported.

23. DBPC Period: Cumulative Prednisone Equivalent Corticosteroid (CS) Dose at Week 52 [Week 52]

    Cumulative Prednisone-equivalent Corticosteroid (CS) Dose was calculated at Week 52.

24. DBPC Period: Number of Participants With a Sustained Reduction of Oral Corticosteroids (OCS) Dose to 7.5 mg Prednisone Equivalent Per Day or Less With Response Based on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Week 52 [Week 52]

    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).

25. DBPC Period: Number of Participants With a Sustained Reduction of Oral Corticosteroids (OCS) Dose to 7.5 mg Prednisone Equivalent Per Day or Less With Response Based on Systemic Lupus Erythematosus Responder Index 6 (SRI-6) at Week 52 [Week 52]

    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).

26. DBPC Period: Number of Participants With a Sustained Reduction of Oral Corticosteroids (OCS) Dose to 7.5 mg Prednisone Equivalent Per Day or Less With Response Based on SRI-4 at Week 52 in Serologically Active Subgroup [Week 52]

    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 very well(0)-very poor(100).

27. DBPC Period: Number of Participants With Lupus Low Disease Activity State (LLDAS) at Week 52 [Week 52]

    Lupus low disease activity state will be measured as: SLEDAI-2K <= 4; No activity in any major organ systems (renal, central nervous system, cardiopulmonary, vasculitis, fever); No new features of disease activity compared with the previous assessment; Prednisone-equivalent <= 7.5 milligram per day; Unchanged background immunosuppressive therapy.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Eligible male and female participants, aged 18 to 75 years

• Must have diagnosis of SLE with either the Systemic Lupus International Collaborating Clinics (SLICC) criteria for SLE, or at least four of the 11 American College of Rheumatology (ACR) classification criteria for SLE, of at least six months duration prior to Screening

• SLEDAI-2K total score greater than or equal to (>=) 6 (including clinical SLEDAI greater than or equal to (>=) 4) at Screening Visit

• And be positive for anti-double-stranded Deoxyribonucleic Acid (DNA) and/or anti-nuclear antibody (ANA greater than or equal to (>=) 1:80) and/or anti-Smith (anti-Sm) antibody at the time of Screening

• Other protocol defined inclusion criteria could apply

Exclusion Criteria:

• Participants are not eligible for this study if they have active, clinically significant interstitial lung disease or pulmonary arterial hypertension

• Proteinuria (urine protein to creatinine ratio [UPCR] > 4 mg/mg)

• Acutely worsened renal function

• Central nervous system SLE

• Or within two weeks prior to Screening or during Screening: use of oral corticosteroids greater than (>) 30 mg daily prednisone equivalent

• Use of injectable corticosteroids, or change in dose of corticosteroids.

• Other protocol defined exclusion criteria could apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pinnacle Research Group LLC	Anniston	Alabama	United States	36207
2	Arizona Arthritis & Rheumatology Associates, P.C.	Mesa	Arizona	United States	85210
3	Arizona Arthritis & Rheumatology Associates, P.C.	Phoenix	Arizona	United States	85032
4	Advanced Research Center, Inc.	Anaheim	California	United States	92805
5	Wallace Rheumatic Study Center	Beverly Hills	California	United States	90211
6	Medvin Clinical Research	Covina	California	United States	91722
7	Southern California Permanent Medical Group	Fontana	California	United States	92335
8	Global Research Management	Glendale	California	United States	91204
9	University of Southern California	Los Angeles	California	United States	90033
10	East Bay Rheumatology Medical Group, Inc.	San Leandro	California	United States	94578
11	Inland Rheumatology Clinical Trials, Inc.	Upland	California	United States	91786
12	Nazanin Firooz, MD Inc.	West Hills	California	United States	91307
13	University of Colorado Denver Anschutz Medical Campus	Aurora	Colorado	United States	80045
14	Yale School Of Medicine	New Haven	Connecticut	United States	06519
15	Clinical Research of West Florida - Corporate	Clearwater	Florida	United States	33765
16	Omega Research Consultants	DeBary	Florida	United States	32713
17	Center for Rheumatology, Immunology & Arthritis	Fort Lauderdale	Florida	United States	33309
18	Hope Clinical Trials	Miami	Florida	United States	33165
19	IRIS Research and Development	Plantation	Florida	United States	33324
20	McIlwain Medical Group, PA	Tampa	Florida	United States	33614
21	Meridien Research, Inc.	Tampa	Florida	United States	33634
22	Marietta Rheumatology Associates, PC	Marietta	Georgia	United States	30060
23	The University of Chicago Medicine	Chicago	Illinois	United States	60637
24	LSU Health Sciences Center Gastroenterology	Shreveport	Louisiana	United States	71103
25	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
26	Henry Ford Health System	Detroit	Michigan	United States	48202
27	AA MRC LLC Ahmed Arif Medical Research Center	Flint	Michigan	United States	48439
28	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
29	Washington University in St. Louis	Saint Louis	Missouri	United States	63110
30	Montefiore Medical Center PRIME	Bronx	New York	United States	10461
31	Hospital for Special Surgery	New York	New York	United States	10021
32	SUNY Upstate Medical Center	Syracuse	New York	United States	13210
33	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
34	Medication Management, LLC	Greensboro	North Carolina	United States	27408
35	Allegheny-Singer Research Institute	Pittsburgh	Pennsylvania	United States	15224
36	Innovative Clinical Research, LLC	Greenville	South Carolina	United States	29601
37	Metroplex Clinical Research Center, LLC	Dallas	Texas	United States	75231
38	Accurate Clinical Research, Inc.	Houston	Texas	United States	77034
39	Accurate Clinical Management - Brionez	Houston	Texas	United States	77084
40	Medical Center Research, LLC Webster Office	Pearland	Texas	United States	77584
41	DM Clinical Research	Tomball	Texas	United States	77375
42	FSAEI HE " First Moscow State Medical University n.a. I.M. Sechenov" of the MoH of the RF	Seattle	Washington	United States
43	Instituto de Investigaciones Clinicas	Mar del Plata	Buenos Aires	Argentina
44	Instituto de Investigaciones Clinicas Quilmes	Quilmes	Buenos Aires	Argentina
45	Centro Medico Privado de Reumatologia	San Miguel de Tucuman	Tucuman	Argentina
46	Investigaciones Clinicas Tucuman	San Miguel de Tucuman	Tucuman	Argentina
47	Centro Integral de Reumatologia	San Miguel de Tucumán	Tucuman	Argentina
48	APRILLUS	Ciudad Autonoma Buenos aires		Argentina
49	Centro Medico Dra Laura Maffei Investigacion Clinica Aplicada	Ciudad Autonoma Buenos Aires		Argentina
50	Clinica Adventista Belgrano	Ciudad Autonoma Buenos Aires		Argentina
51	Hospital Britanico de Buenos Aires	Ciudad Autonoma Buenos Aires		Argentina
52	Hospital General de Agudos Dr. J. M. Ramos Mejia	Ciudad Autonoma Buenos Aires		Argentina
53	Sanatorio Allende	Cordoba		Argentina
54	Instituto de Reumatologia	Mendoza		Argentina
55	Cordis S.A.	Salta		Argentina
56	Centro Polivalente de Asistencia e Inv. Clinica CER	San Juan		Argentina
57	UMHAT "Pulmed" OOD	Plovdiv		Bulgaria
58	MHAT - Ruse, AD	Ruse		Bulgaria
59	Medizinski Zentar-1-Sevlievo EOOD	Sevlievo		Bulgaria
60	Medical Center "Excelsior", OOD	Sofia		Bulgaria
61	Medical Center Comac Medical EOOD	Sofia		Bulgaria
62	UMHAT "SofiaMed", OOD	Sofia		Bulgaria
63	UMHAT "Sv. Ivan Rilski", EAD	Sofia		Bulgaria
64	Corporacion de Beneficencia Osorno	Osorno		Chile
65	Centro de Estudios Reumatologicos	Santiago		Chile
66	Centro Medico Prosalud	Santiago		Chile
67	Interin	Santiago		Chile
68	Psicomedica Clinical and Research Group	Santiago		Chile
69	Quantum Research Santiago	Santiago		Chile
70	Centro de Reumatologia y Ortopedia SAS	Barranquilla		Colombia
71	Clínica de la Costa Ltda.	Barranquilla		Colombia
72	Fundacion Instituto de Reumatologia Fernando Chalem	Bogota		Colombia
73	Simedics Ips Sas	Bogotá		Colombia
74	Servimed S.A.S.	Bucaramanga		Colombia
75	Charite Universitaetsmedizin Berlin - Campus Charite Mitte	Berlin		Germany
76	Humanitas Research Hospital	Rozzano	Milano	Italy
77	Ospedale San Raffaele	Milano		Italy
78	Azienda Ospedaliera Universitaria- Università degli Studi della Campania "Luigi Vanvitelli"	Napoli		Italy
79	Arcispedale S. Maria Nuova Azienda Ospedaliera di Reggio Emilia	Reggio Emilia		Italy
80	Policlinico Universitario Agostino Gemelli	Roma		Italy
81	Ehime University Hospital	Toon-shi	Ehime-Ken	Japan
82	Tobata General Hospital	Kitakyushu-shi	Fukuoka-Ken	Japan
83	University of Occupational and Environmental Health Hospital	Kitakyushu-shi	Fukuoka-Ken	Japan
84	NHO Asahikawa Medical Center	Asahikawa-shi	Hokkaido	Japan
85	Kanazawa University Hospital	Kanazawa-shi	Ishikawa-Ken	Japan
86	Kagawa University Hospital	Kita-gun	Kagawa-Ken	Japan
87	Eiraku Clinic	Kagoshima-shi	Kagoshima-Ken	Japan
88	Tohoku University Hospital	Sendai-shi	Miyagi-Ken	Japan
89	Seirei Hamamatsu General Hospital	Hamamatsu-shi	Shizuoka-Ken	Japan
90	Dokkyo Medical University Hospital	Shimotsuga-gun	Tochigi-Ken	Japan
91	St. Luke's International Hospital	Chuo-ku	Tokyo-To	Japan
92	Tokyo Metropolitan Tama Medical Center	Fuchu-shi	Tokyo-To	Japan
93	Nihon University Itabashi Hospital	Itabashi-ku	Tokyo-To	Japan
94	Keio University Hospital	Shinjuku-ku	Tokyo-To	Japan
95	Tottori University Hospital	Yonago-shi	Tottori-Ken	Japan
96	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do	Korea, Republic of
97	Ajou University Hospital	Suwon-si	Gyeonggi-do	Korea, Republic of
98	Dong-A University Hospital	Busan		Korea, Republic of
99	Kyungpook National University Hospital	Daegu		Korea, Republic of
100	Konkuk University Medical Center	Seoul		Korea, Republic of
101	Severance Hospital, Yonsei University	Seoul		Korea, Republic of
102	The Catholic University of Korea, Yeouido St. Mary's Hospital	Seoul		Korea, Republic of
103	Hospital Pakar Sultanah Fatimah	Muar	Johor	Malaysia
104	Hospital Umum Sarawak	Kuching	Sarawak	Malaysia
105	Hospital Selayang	Batu Caves	Selangor	Malaysia
106	International Medical University (IMU) Healthcare	Bukit Jalil	Selangor	Malaysia
107	Hospital Kuala Lumpur	Kuala Lumpur		Malaysia
108	CAP Research	Solferino-Phoenix		Mauritius
109	Unidad de Investigacion de las Enfermedades Reumaticas	Cuauhtemoc	Distrito Federal	Mexico
110	Clinstile, S.A. de C.V.	Mexico	Distrito Federal	Mexico
111	Clinical Research Institute S.C.	Tlalnepantla	Estado De Mexico	Mexico
112	Morales Vargas Centro de Investigacion, S.C.	Leon	Guanajuato	Mexico
113	Clinica de Investigacion en Reumatologia y Obesidad S.C.	Guadalajara	Jalisco	Mexico
114	Unidad de Investigacion en Enfermedades Cronico Degenerativas SC	Guadalajara	Jalisco	Mexico
115	Accelerium S. de R.L. de C.V.	Monterrey	Nuevo León	Mexico
116	Hospital Central Dr Ignacio Morones Prieto	San Luis Potosi	San Luis Potos	Mexico
117	Investigacion y Biomedicina de Chihuahua, S.C.	Chihuahua		Mexico
118	Hogar Clínica San Juan de Dios - Arequipa	Arequipa		Peru
119	Clinica El Golf	Lima		Peru
120	Clinica Medica Cayetano Heredia	Lima		Peru
121	Clinica San Juan Bautista	Lima		Peru
122	Clinica Vesalio	Lima		Peru
123	GINOBS SA. Instituto de Ginecologia y Reproduccion	Lima		Peru
124	Hospital Nacional Cayetano Heredia	Lima		Peru
125	University of Washington Medical Center	Lima		Peru
126	ICCV Research Instituto del Cerebro y la Columna Vertebral	Miraflores		Peru
127	Angeles University Foundation Medical Center	Angeles City, Pampanga		Philippines
128	Mary Mediatrix Medical Center	Batangas		Philippines
129	De La Salle University Medical Center	Dasmariñas City, Cavite		Philippines
130	Davao Doctors Hospital	Davao City		Philippines
131	Southern Philippines Medical Center	Davao City		Philippines
132	Iloilo Doctors Hospital	Iloilo City		Philippines
133	St. Luke's Medical Center	Quezon City		Philippines
134	CERMED	Bialystok		Poland
135	Szpital Uniwersytecki nr 2 im.dr J. Biziela	Bydgoszcz		Poland
136	Centrum Reumatologiczne Indywidualna Specjalistyczna Praktyka Lekarska lek. Barbara Bazela	Elblag		Poland
137	Centrum Medyczne Plejady	Krakow		Poland
138	Nzoz Atopia	Krakow		Poland
139	Rheuma Medicus Zaklad	Warsawa		Poland
140	Spitalul Clinic "Dr.I. Cantacuzino"	Bucuresti		Romania
141	Spitalul Clinic "Sf. Maria"	Bucuresti		Romania
142	S.C Mediab S.R.L	Tirgu Mures		Romania
143	LLC "Alliance Biomedical - Ural Group"	Izhevsk		Russian Federation
144	TSBIH "Krasnoyarsk Interdistrict Clinical Hospital of Emergency Medical Care n.a. N.S. Karpovich	Krasnoyarsk		Russian Federation
145	HMA - Hospital Maria Auxiliadora	Moscow		Russian Federation
146	Ultramed	Omsk		Russian Federation
147	LLC Medical Sanitary Unit#157	Saint-Petersburg		Russian Federation
148	SPb SBIH "Clinical Rheumatological Hospital # 25"	Saint-Petersburg		Russian Federation
149	SIH "Saratov City Clinical Hospital # 12"	Saratov		Russian Federation
150	Research Institute of Emergency Medical Care	St. Petersburg		Russian Federation
151	Nebbiolo LLC	Tomsk		Russian Federation
152	Wits Clinical Research	Johannesburg	Gauteng	South Africa
153	Winelands Medical Research Centre	Stellenbosch	Western Cape	South Africa
154	Naidoo, A - Netcare Umhlanga Hospital	Durban		South Africa	4319
155	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung		Taiwan
156	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung		Taiwan
157	Taichung Veterans General Hospital	Taichung		Taiwan

Sponsors and Collaborators

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

Investigators

• Study Director: Medical Responsible, EMD Serono Research & Development Institute, Inc., a business of Merck KGaA, Darmstadt, Germany

Study Documents (Full-Text)

• Study Protocol - May 22, 2018
• Statistical Analysis Plan - Jun 11, 2020

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: EMD Serono Research & Development Institute, Inc.
• ClinicalTrials.gov Identifier: NCT02975336
• Other Study ID Numbers: MS200527-0018; 2016-002950-19
• First Posted: Nov 29, 2016
• Last Update Posted: Apr 12, 2021
• Last Verified: Mar 1, 2021

• Keywords provided by EMD Serono Research & Development Institute, Inc.: Systemic Lupus Erythematosus; M2951; Placebo; Dose response; Oral Corticosteroids; Safety; Efficacy; Autoimmune And Inflammatory Disorders
• Additional relevant MeSH terms: Lupus Erythematosus, Systemic

Study Results

Participant Flow

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.

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
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
Period Title: DBPC (52 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

Baseline Characteristics

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
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 Participants	117	118	117	117	469
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	40.2 (12.49)	38.8 (12.45)	41.5 (12.52)	42.2 (11.78)	40.7 (12.34)
Sex: Female, Male (Count of Participants)
Female	110 94%	112 94.9%	111 94.9%	112 95.7%	445 94.9%
Male	7 6%	6 5.1%	6 5.1%	5 4.3%	24 5.1%
Ethnicity (NIH/OMB) (Count of 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%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	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%
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%
Unknown or Not Reported	18 15.4%	16 13.6%	17 14.5%	9 7.7%	60 12.8%

Outcome Measures

1. Primary Outcome

Title	DBPC Period: Number of Participants With Response Based on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Week 52
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

Outcome Measure Data

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
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.
Measure Participants	114	115	116	114
Count of Participants [Participants]	52 44.4%	64 54.2%	60 51.3%	55 47%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5462
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.55
	Confidence Interval	(2-Sided) 95%; 0.91 to 2.64
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5462
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.29
	Confidence Interval	(2-Sided) 95%; 0.76 to 2.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5462
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.13
	Confidence Interval	(2-Sided) 95%; 0.67 to 1.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	DBPC Period: Number of Participants With Response Based on Systemic Lupus Erythematosus Responder Index 6 (SRI-6) at Week 52
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

Outcome Measure Data

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
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.
Measure Participants	56	54	65	55
Count of Participants [Participants]	22 18.8%	27 22.9%	30 25.6%	24 20.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5462
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.50
	Confidence Interval	(2-Sided) 95%; 0.69 to 3.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5462
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.42
	Confidence Interval	(2-Sided) 95%; 0.68 to 2.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5462
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.27
	Confidence Interval	(2-Sided) 95%; 0.59 to 2.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

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)
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

Outcome Measure Data

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
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.
Measure Participants	117	118	117	117
Any TEAEs	96 82.1%	103 87.3%	100 85.5%	99 84.6%
Any serious TEAE	10 8.5%	13 11%	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)
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

Outcome Measure Data

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
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.
Measure Participants	117	118	117	117
Grade 1	76 65%	80 67.8%	79 67.5%	76 65%
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%	2 1.7%
Grade 5	0 0%	1 0.8%	1 0.9%	0 0%

5. Primary Outcome

Title	DBPC Period: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
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

Outcome Measure Data

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
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.
Measure Participants	117	118	117	117
Count of Participants [Participants]	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
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

Outcome Measure Data

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
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.
Measure Participants	117	118	117	117
Count of Participants [Participants]	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
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

Outcome Measure Data

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
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.
Measure Participants	117	118	117	117
Count of Participants [Participants]	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
Description	Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 2.
Time Frame	Week 2

Outcome Measure Data

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
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.
Measure Participants	114	116	115	113
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
Description	Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 4.
Time Frame	Week 4

Outcome Measure Data

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
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.
Measure Participants	114	114	114	115
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
Description	Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 12.
Time Frame	Week 12

Outcome Measure Data

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
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.
Measure Participants	110	106	110	105
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
Description	Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 24.
Time Frame	Week 24

Outcome Measure Data

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
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.
Measure Participants	96	97	101	96
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
Description	Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 36.
Time Frame	Week 36

Outcome Measure Data

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
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.
Measure Participants	92	91	97	86
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
Description	Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 52
Time Frame	Week 52

Outcome Measure Data

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
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.
Measure Participants	78	83	85	76
IgG	15.21 (5.105)	13.90 (4.087)	14.32 (4.542)	13.01 (3.723)
IgA	2.82 (1.438)	2.95 (1.596)	3.17 (1.596)	2.95 (1.159)
IgM	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
Description	Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 56
Time Frame	Week 56

Outcome Measure Data

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
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.
Measure Participants	37	36	31	33
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
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

Outcome Measure Data

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
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.
Measure Participants	98	99	99	99
Mean (Standard Deviation) [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
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

Outcome Measure Data

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
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.
Measure Participants	89	90	87	88
Mean (Standard Deviation) [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
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

Outcome Measure Data

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
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.
Measure Participants	68	66	76	66
Mean (Standard Deviation) [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
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

Outcome Measure Data

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
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.
Measure Participants	35	30	27	30
Mean (Standard Deviation) [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
Description	Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
Time Frame	Baseline and Week 2

Outcome Measure Data

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
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.
Measure Participants	114	116	115	113
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
Description	Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
Time Frame	Baseline and Week 4

Outcome Measure Data

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
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.
Measure Participants	114	114	114	115
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
Description	Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
Time Frame	Baseline and Week 12

Outcome Measure Data

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
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.
Measure Participants	110	106	110	105
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
Description	Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
Time Frame	Baseline and Week 24

Outcome Measure Data

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
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.
Measure Participants	96	97	101	96
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
Description	Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
Time Frame	Baseline and Week 36

Outcome Measure Data

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
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.
Measure Participants	92	91	97	86
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
Description	Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
Time Frame	Baseline and Week 52

Outcome Measure Data

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
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.
Measure Participants	78	83	85	76
IgG	0.41 (2.898)	0.29 (2.361)	0.35 (2.688)	-0.31 (2.344)
IgA	0.19 (0.420)	0.32 (0.492)	0.39 (0.767)	0.18 (0.469)
IgM	-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
Description	Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
Time Frame	Baseline and Week 56

Outcome Measure Data

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
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.
Measure Participants	37	36	31	33
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
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

Outcome Measure Data

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
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.
Measure Participants	90	88	88	91
Mean (Standard Deviation) [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
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

Outcome Measure Data

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
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.
Measure Participants	80	82	73	81
Mean (Standard Deviation) [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
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

Outcome Measure Data

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
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.
Measure Participants	57	60	63	60
Mean (Standard Deviation) [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
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

Outcome Measure Data

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
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.
Measure Participants	30	27	24	24
Mean (Standard Deviation) [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
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

Outcome Measure Data

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
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.
Measure Participants	14	16	11	12
Median (Full Range) [Days]	NA	NA	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7034
	Comments
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.17
	Confidence Interval	(2-Sided) 95%; 0.57 to 2.40
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5462
	Comments
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.69
	Confidence Interval	(2-Sided) 95%; 0.31 to 1.52
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5462
	Comments
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95%; 0.42 to 1.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
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

Outcome Measure Data

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
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.
Measure Participants	59	65	60	63
Count of Participants [Participants]	28 23.9%	38 32.2%	29 24.8%	34 29.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5462
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.52
	Confidence Interval	(2-Sided) 95%; 0.74 to 3.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5462
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95%; 0.49 to 2.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5462
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.35
	Confidence Interval	(2-Sided) 95%; 0.65 to 2.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
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

Outcome Measure Data

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
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.
Measure Participants	59	65	60	63
Count of Participants [Participants]	17 14.5%	25 21.2%	23 19.7%	23 19.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2434
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.60
	Confidence Interval	(2-Sided) 95%; 0.73 to 3.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2389
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.62
	Confidence Interval	(2-Sided) 95%; 0.73 to 3.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1952
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.71
	Confidence Interval	(2-Sided) 95%; 0.76 to 3.85
	Parameter Dispersion	Type: Value:
	Estimation Comments

33. Secondary Outcome

Title	DBPC Period: Time to First British Isles Lupus Assessment Group (BILAG) A or 2B Moderate to Severe Flare
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

Outcome Measure Data

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
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.
Measure Participants	18	27	19	19
Median (Full Range) [Days]	NA	NA	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0987
	Comments
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.59
	Confidence Interval	(2-Sided) 95%; 0.87 to 2.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9201
	Comments
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.51 to 1.85
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5645
	Comments
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.15
	Confidence Interval	(2-Sided) 95%; 0.60 to 2.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
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

Outcome Measure Data

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
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.
Measure Participants	114	115	116	114
Count of Participants [Participants]	41 35%	35 29.7%	37 31.6%	33 28.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3743
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.77
	Confidence Interval	(2-Sided) 95%; 0.44 to 1.37
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6445
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95%; 0.50 to 1.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2634
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.72
	Confidence Interval	(2-Sided) 95%; 0.41 to 1.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

35. Secondary Outcome

Title	DBPC Period: Annualized Flare Rate
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

Outcome Measure Data

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
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.
Measure Participants	114	115	116	114
Number (95% Confidence Interval) [Annualized flare rate ratio]	0.15	0.23	0.13	0.19

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2989
	Comments	Nominal p-value
	Method	Negative binomial regression
	Comments
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	1.59
	Confidence Interval	(2-Sided) 95%; 0.66 to 3.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7325
	Comments	Nominal p-value
	Method	Negative binomial regression
	Comments
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.33 to 2.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5910
	Comments	Nominal p-value
	Method	Negative binomial regression
	Comments
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	1.29
	Confidence Interval	(2-Sided) 95%; 0.51 to 3.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
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

Outcome Measure Data

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
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.
Measure Participants	114	115	116	114
Count of Participants [Participants]	26 22.2%	32 27.1%	39 33.3%	28 23.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3635
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.33
	Confidence Interval	(2-Sided) 95%; 0.72 to 2.47
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0329
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.94
	Confidence Interval	(2-Sided) 95%; 1.06 to 3.56
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7619
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.10
	Confidence Interval	(2-Sided) 95%; 0.59 to 2.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
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

Outcome Measure Data

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
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.
Measure Participants	114	115	116	114
Count of Participants [Participants]	42 35.9%	50 42.4%	52 44.4%	41 35%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2642
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.36
	Confidence Interval	(2-Sided) 95%; 0.79 to 2.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1489
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.49
	Confidence Interval	(2-Sided) 95%; 0.87 to 2.57
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9285
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.56 to 1.70
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
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

Outcome Measure Data

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
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.
Measure Participants	111	115	115	113
Week 4	-1 (1.9)	-1 (2.1)	0 (1.9)	-1 (2.2)
Week 8	-2 (3.1)	-2 (3.2)	-2 (3.0)	-2 (3.2)
Week 12	-3 (3.8)	-3 (3.3)	-3 (3.2)	-3 (3.4)
Week 16	-4 (3.7)	-3 (3.4)	-3 (3.4)	-3 (3.6)
Week 20	-4 (4.1)	-4 (3.8)	-4 (3.4)	-4 (3.4)
Week 24	-4 (4.0)	-4 (3.7)	-4 (3.6)	-3 (3.4)
Week 28	-4 (3.9)	-4 (3.6)	-4 (3.5)	-4 (3.5)
Week 32	-4 (4.0)	-4 (3.5)	-4 (3.7)	-4 (3.4)
Week 36	-4 (4.3)	-5 (3.5)	-5 (3.6)	-4 (3.5)
Week 40	-5 (4.1)	-5 (3.6)	-5 (3.8)	-4 (3.3)
Week 44	-4 (4.0)	-5 (3.7)	-5 (3.9)	-4 (3.5)
Week 48	-4 (4.1)	-5 (3.7)	-5 (3.8)	-5 (3.3)
Week 52	-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
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

Outcome Measure Data

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
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.
Measure Participants	111	113	115	113
Week 2	-1 (1.9)	-1 (1.6)	0 (1.6)	0 (1.2)
Week 4	-1 (1.9)	-1 (3.5)	-1 (2.4)	-1 (2.2)
Week 8	-2 (2.8)	-1 (4.2)	-1 (2.3)	-1 (2.5)
Week 12	-2 (2.8)	-2 (3.3)	-2 (3.2)	-2 (2.7)
Week 16	-2 (3.1)	-2 (3.9)	-2 (3.3)	-2 (2.7)
Week 20	-3 (3.6)	-3 (4.4)	-3 (3.4)	-2 (2.9)
Week 24	-3 (3.5)	-3 (4.7)	-3 (3.6)	-2 (2.7)
Week 28	-3 (3.7)	-3 (4.6)	-3 (3.4)	-2 (2.7)
Week 32	-3 (3.5)	-3 (4.4)	-3 (3.6)	-3 (3.2)
Week 36	-3 (3.5)	-3 (4.6)	-3 (3.4)	-3 (3.6)
Week 40	-3 (3.0)	-3 (4.6)	-3 (3.6)	-3 (3.8)
Week 44	-3 (3.2)	-3 (4.5)	-3 (3.7)	-3 (3.8)
Week 48	-3 (3.2)	-3 (4.7)	-3 (3.7)	-3 (3.9)
Week 52	-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
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

Outcome Measure Data

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
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.
Measure Participants	76	73	76	70
Count of Participants [Participants]	30 25.6%	29 24.6%	33 28.2%	24 20.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9061
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95%; 0.49 to 1.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6053
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.19
	Confidence Interval	(2-Sided) 95%; 0.61 to 2.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5200
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.80
	Confidence Interval	(2-Sided) 95%; 0.40 to 1.59
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
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

Outcome Measure Data

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
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.
Measure Participants	110	111	109	109
Week 4	-4 (5.8)	-4 (6.1)	-3 (6.3)	-4 (6.2)
Week 8	-6 (6.0)	-5 (7.0)	-6 (6.3)	-6 (6.1)
Week 12	-7 (6.7)	-7 (6.8)	-6 (7.0)	-6 (6.2)
Week 16	-7 (6.9)	-7 (7.6)	-6 (6.8)	-6 (5.9)
Week 20	-7 (6.8)	-7 (7.3)	-7 (7.6)	-6 (6.2)
Week 24	-8 (6.9)	-7 (6.5)	-8 (7.7)	-6 (6.3)
Week 28	-8 (6.7)	-8 (6.9)	-8 (7.4)	-7 (6.2)
Week 32	-9 (6.7)	-8 (7.3)	-8 (7.9)	-7 (6.0)
Week 36	-8 (7.1)	-8 (7.2)	-8 (7.4)	-7 (6.7)
Week 40	-9 (6.8)	-8 (6.7)	-9 (7.7)	-7 (6.6)
Week 44	-9 (7.2)	-9 (7.2)	-9 (7.9)	-7 (6.7)
Week 48	-8 (7.1)	-8 (7.2)	-9 (7.6)	-7 (6.5)
Week 52	-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
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

Outcome Measure Data

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
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.
Measure Participants	111	115	115	113
Week 4	-8 (11.7)	-8 (14.1)	-9 (13.4)	-9 (12.1)
Week 8	-13 (16.2)	-14 (16.5)	-13 (15.5)	-14 (15.9)
Week 12	-18 (17.4)	-18 (18.8)	-19 (18.3)	-18 (16.9)
Week 16	-21 (17.6)	-20 (19.7)	-21 (18.7)	-19 (18.0)
Week 20	-23 (19.2)	-21 (19.5)	-24 (17.9)	-20 (18.6)
Week 24	-24 (17.8)	-24 (20.0)	-25 (19.2)	-21 (18.0)
Week 28	-26 (17.6)	-26 (20.3)	-26 (18.6)	-24 (17.8)
Week 32	-26 (17.8)	-26 (20.8)	-26 (19.0)	-26 (17.5)
Week 36	-26 (17.9)	-26 (20.9)	-29 (18.3)	-26 (18.3)
Week 40	-27 (16.9)	-27 (19.1)	-30 (19.7)	-25 (18.1)
Week 44	-28 (16.6)	-28 (20.1)	-30 (20.7)	-26 (16.6)
Week 48	-29 (16.5)	-29 (19.5)	-32 (18.8)	-28 (18.3)
Week 52	-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
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

Outcome Measure Data

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
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.
Measure Participants	110	114	112	113
Physical Component Summary Score at Week 4	1.2 (5.42)	2.5 (7.40)	3.5 (6.01)	2.2 (5.86)
Physical Component Summary Score at Week 8	1.8 (6.35)	3.5 (7.69)	3.0 (6.61)	2.2 (6.63)
Physical Component Summary Score at Week 12	2.4 (6.44)	3.7 (7.71)	4.2 (6.68)	3.0 (6.99)
Physical Component Summary Score at Week 16	3.3 (7.04)	4.0 (7.56)	4.4 (5.81)	3.4 (6.77)
Physical Component Summary Score at Week 24	3.4 (7.08)	4.6 (7.57)	5.4 (7.63)	2.8 (7.15)
Physical Component Summary Score at Week 32	3.5 (8.03)	3.8 (7.36)	5.4 (7.24)	3.8 (6.89)
Physical Component Summary Score at Week 40	4.2 (7.11)	4.6 (7.97)	5.7 (7.76)	4.1 (8.59)
Physical Component Summary Score at Week 52	3.7 (8.32)	5.4 (7.05)	6.5 (8.58)	4.8 (7.76)
Mental Component Summary Score at Week 4	3.9 (9.38)	1.7 (9.25)	1.9 (7.93)	2.4 (7.68)
Mental Component Summary Score at Week 8	2.5 (8.59)	2.2 (8.81)	1.6 (8.48)	3.6 (9.04)
Mental Component Summary Score at Week 12	3.1 (10.07)	3.1 (8.45)	0.8 (10.39)	2.9 (8.89)
Mental Component Summary Score at Week 16	3.6 (9.84)	2.5 (8.39)	2.8 (9.39)	2.9 (9.13)
Mental Component Summary Score at Week 24	2.9 (9.75)	2.4 (8.41)	3.4 (9.68)	2.7 (8.87)
Mental Component Summary Score at Week 32	3.5 (8.55)	1.8 (9.51)	2.8 (9.71)	4.3 (9.03)
Mental Component Summary Score at Week 40	4.5 (8.81)	1.5 (10.55)	3.2 (9.81)	4.0 (9.85)
Mental Component Summary Score at Week 52	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
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

Outcome Measure Data

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
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.
Measure Participants	110	114	112	113
Week 4	0.036 (0.1626)	0.045 (0.1931)	0.036 (0.1618)	0.038 (0.1908)
Week 8	0.034 (0.2164)	0.064 (0.2505)	0.046 (0.1842)	0.061 (0.1603)
Week 12	0.061 (0.2014)	0.070 (0.2189)	0.055 (0.1912)	0.065 (0.1732)
Week 16	0.083 (0.1818)	0.072 (0.2252)	0.067 (0.2287)	0.056 (0.1738)
Week 24	0.080 (0.1901)	0.067 (0.2271)	0.086 (0.2110)	0.055 (0.1817)
Week 32	0.083 (0.1758)	0.067 (0.2262)	0.075 (0.2009)	0.071 (0.1941)
Week 40	0.093 (0.1521)	0.061 (0.1850)	0.090 (0.1853)	0.084 (0.2172)
Week 52	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
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

Outcome Measure Data

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
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.
Measure Participants	110	114	112	113
Week 4	3 (16.8)	2 (19.0)	4 (17.6)	4 (18.2)
Week 8	3 (18.8)	6 (20.0)	4 (14.5)	6 (16.5)
Week 12	5 (19.7)	6 (17.4)	5 (17.2)	4 (16.8)
Week 16	7 (19.3)	5 (18.1)	6 (18.5)	4 (15.5)
Week 24	7 (18.7)	5 (18.4)	9 (20.4)	4 (17.3)
Week 32	8 (17.2)	4 (21.1)	7 (17.8)	7 (16.6)
Week 40	8 (18.1)	6 (18.1)	10 (19.5)	8 (18.9)
Week 52	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
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

Outcome Measure Data

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
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.
Measure Participants	110	114	112	113
Physical Health Week 4	1.9 (12.58)	4.7 (17.68)	4.0 (14.04)	3.5 (13.43)
Physical Health Week 8	2.8 (15.20)	6.3 (19.94)	3.8 (17.64)	4.6 (14.69)
Physical Health Week 12	4.8 (16.75)	6.7 (19.78)	5.6 (15.95)	5.7 (14.94)
Physical Health Week 16	6.6 (17.45)	6.1 (18.71)	7.4 (17.61)	6.2 (15.59)
Physical Health Week 24	6.9 (17.17)	7.2 (18.59)	8.4 (20.47)	6.1 (13.63)
Physical Health Week 32	5.7 (16.82)	6.7 (19.45)	9.4 (17.21)	7.0 (16.21)
Physical Health Week 40	7.6 (15.32)	8.2 (17.38)	9.6 (19.10)	7.1 (17.98)
Physical Health Week 52	7.1 (20.39)	9.0 (18.44)	11.6 (19.88)	7.9 (18.73)
Pain Week 4	3.6 (16.30)	6.7 (21.81)	9.0 (20.90)	5.7 (16.26)
Pain Week 8	4.8 (18.71)	9.9 (24.65)	7.3 (21.76)	6.7 (18.31)
Pain Week 12	7.5 (19.04)	8.8 (24.00)	9.8 (23.35)	5.5 (14.73)
Pain Week 16	9.4 (18.58)	8.3 (25.60)	10.5 (26.33)	6.9 (15.47)
Pain Week 24	9.4 (19.95)	9.3 (24.31)	13.0 (28.18)	6.2 (17.02)
Pain Week 32	6.7 (23.74)	9.2 (24.60)	12.8 (22.87)	8.7 (17.18)
Pain Week 40	11.0 (19.43)	10.9 (23.68)	15.3 (23.81)	9.6 (20.51)
Pain Week 52	10.2 (21.37)	12.9 (22.64)	14.9 (26.11)	9.6 (19.99)
Planning Week 4	4.8 (20.14)	4.9 (19.64)	5.4 (24.30)	4.6 (18.73)
Planning Week 8	5.5 (23.32)	8.4 (23.25)	5.8 (25.14)	3.9 (22.98)
Planning Week 12	7.8 (23.58)	5.8 (23.39)	6.8 (25.74)	5.1 (20.55)
Planning Week 16	8.3 (21.65)	5.3 (24.12)	6.5 (28.00)	6.3 (22.91)
Planning Week 24	7.9 (22.92)	8.1 (23.55)	11.5 (29.08)	5.6 (21.79)
Planning Week 32	6.5 (24.82)	7.6 (22.66)	9.9 (25.90)	6.9 (22.07)
Planning Week 40	9.0 (20.69)	7.8 (23.19)	11.6 (26.17)	8.0 (23.52)
Planning Week 52	9.9 (22.38)	7.0 (23.12)	9.9 (28.29)	10.5 (21.59)
Intimate Relationship Week 4	3.4 (26.11)	1.6 (28.29)	4.7 (24.06)	3.2 (24.06)
Intimate Relationship Week 8	8.2 (30.31)	4.2 (28.44)	9.7 (29.10)	3.7 (18.73)
Intimate Relationship Week 12	5.5 (27.31)	4.7 (25.65)	2.3 (30.37)	6.4 (21.32)
Intimate Relationship Week 16	8.8 (26.77)	1.6 (30.76)	3.8 (32.46)	4.2 (22.99)
Intimate Relationship Week 24	6.4 (30.12)	2.1 (28.79)	6.7 (30.76)	5.3 (26.29)
Intimate Relationship Week 32	2.5 (28.77)	1.3 (31.78)	6.5 (29.41)	1.4 (27.86)
Intimate Relationship Week 40	12.0 (27.59)	6.6 (27.91)	6.4 (32.53)	7.8 (22.72)
Intimate Relationship Week 52	7.4 (26.48)	4.4 (28.36)	8.4 (29.58)	8.9 (24.52)
Burden to Others Week 4	5.8 (23.83)	5.2 (22.84)	6.8 (24.85)	2.2 (24.24)
Burden to Others Week 8	5.6 (22.42)	9.3 (27.17)	5.7 (25.80)	8.0 (25.79)
Burden to Others Week 12	8.6 (25.86)	6.7 (28.00)	7.4 (25.93)	7.3 (24.74)
Burden to Others Week 16	11.8 (26.17)	8.1 (23.32)	6.7 (25.80)	7.4 (24.30)
Burden to Others Week 24	10.3 (28.68)	9.0 (24.12)	11.8 (27.15)	5.8 (26.21)
Burden to Others Week 32	10.6 (29.42)	6.8 (24.09)	9.6 (27.14)	8.4 (28.21)
Burden to Others Week 40	16.1 (25.07)	12.4 (21.91)	12.4 (28.74)	12.1 (25.78)
Burden to Others Week 52	15.3 (26.96)	10.7 (22.13)	13.0 (30.04)	10.5 (25.89)
Emotional Health Week 4	6.4 (15.37)	4.7 (18.48)	4.2 (18.45)	1.8 (16.73)
Emotional Health Week 8	4.5 (15.15)	7.0 (19.26)	2.3 (19.51)	5.3 (15.53)
Emotional Health Week 12	6.3 (17.23)	7.6 (21.08)	4.9 (20.99)	4.7 (16.39)
Emotional Health Week 16	8.3 (15.86)	7.5 (19.59)	7.4 (18.56)	6.2 (18.32)
Emotional Health Week 24	7.1 (17.31)	5.6 (24.02)	8.9 (20.97)	4.3 (20.04)
Emotional Health Week 32	6.3 (17.07)	4.3 (23.55)	9.0 (22.66)	6.0 (20.56)
Emotional Health Week 40	8.4 (16.08)	8.3 (19.94)	7.6 (21.52)	6.7 (19.14)
Emotional Health Week 52	8.5 (17.43)	6.4 (21.31)	8.2 (22.77)	7.6 (18.80)
Body Image Week 4	3.1 (17.70)	8.4 (24.41)	2.5 (24.60)	4.0 (18.79)
Body Image Week 8	5.7 (18.37)	7.5 (23.40)	-1.3 (27.06)	6.5 (17.30)
Body Image Week 12	6.5 (18.57)	7.1 (21.07)	2.3 (26.86)	6.6 (16.53)
Body Image Week 16	6.7 (18.10)	7.6 (23.11)	-0.4 (25.31)	5.7 (20.39)
Body Image Week 24	6.7 (20.84)	10.2 (20.47)	5.8 (27.31)	6.7 (21.80)
Body Image Week 32	5.1 (20.08)	8.1 (23.71)	3.3 (24.99)	5.8 (21.54)
Body Image Week 40	7.7 (14.11)	8.2 (23.99)	4.6 (26.67)	9.0 (18.31)
Body Image Week 52	6.6 (16.92)	9.8 (21.46)	5.1 (27.30)	7.8 (21.56)
Fatigue Week 4	4.4 (16.71)	4.3 (18.98)	6.2 (19.91)	3.9 (17.08)
Fatigue Week 8	5.0 (19.22)	7.1 (21.31)	4.9 (20.61)	4.5 (16.78)
Fatigue Week 12	6.7 (18.22)	5.8 (21.30)	7.3 (23.11)	5.0 (16.08)
Fatigue Week 16	7.7 (17.61)	6.6 (21.39)	7.1 (24.16)	4.1 (15.81)
Fatigue Week 24	7.5 (19.06)	4.8 (23.34)	9.0 (26.00)	3.6 (14.20)
Fatigue Week 32	7.0 (19.20)	3.7 (22.71)	8.5 (22.96)	4.1 (17.24)
Fatigue Week 40	11.3 (20.03)	6.1 (25.28)	11.0 (25.18)	5.3 (16.73)
Fatigue Week 52	8.9 (21.15)	4.5 (24.78)	11.2 (22.56)	6.7 (17.89)

47. Secondary Outcome

Title	DBPC Period: Number of Participants With Patient Global Impression of Change (PGIC) Scale Score of Any Improvement, no Change and Any Worsening
Description	The PGIC is a self-rated scale that asks the participant to describe the change in activity limitations, symptoms, emotions, and overall quality of life (QoL) related to the participants painful condition on the following scale: 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse) and 7 (very much worse). Number of participants in the PGIC categories of any improvement (that is PGIC scale score 1, 2 or 3), no change (that is PGIC scale score 4) and any worsening (that is PGIC scale score 5, 6 or 7) are reported.
Time Frame	Week 4, 8, 12, 16, 24, 32, 40, and 52

Outcome Measure Data

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,"Number Analyzed" signified those participants who were evaluable 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
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.
Measure Participants	112	114	113	113
Any Improvement	69 59%	78 66.1%	81 69.2%	71 60.7%
No Change	33 28.2%	27 22.9%	23 19.7%	34 29.1%
Any Worsening	8 6.8%	9 7.6%	8 6.8%	8 6.8%
Missing	2 1.7%	0 0%	1 0.9%	0 0%
Any Improvement	80 68.4%	81 68.6%	85 72.6%	75 64.1%
No Change	22 18.8%	18 15.3%	19 16.2%	28 23.9%
Any Worsening	5 4.3%	9 7.6%	5 4.3%	3 2.6%
Missing	3 2.6%	2 1.7%	1 0.9%	3 2.6%
Any Improvement	78 66.7%	82 69.5%	81 69.2%	77 65.8%
No Change	23 19.7%	13 11%	15 12.8%	20 17.1%
Any Worsening	5 4.3%	7 5.9%	7 6%	4 3.4%
Missing	2 1.7%	3 2.5%	4 3.4%	3 2.6%
Any Improvement	75 64.1%	81 68.6%	87 74.4%	79 67.5%
No Change	23 19.7%	13 11%	16 13.7%	15 12.8%
Any Worsening	3 2.6%	7 5.9%	2 1.7%	2 1.7%
Missing	3 2.6%	0 0%	0 0%	2 1.7%
Any Improvement	67 57.3%	77 65.3%	87 74.4%	73 62.4%
No Change	23 19.7%	12 10.2%	7 6%	17 14.5%
Any Worsening	6 5.1%	6 5.1%	5 4.3%	5 4.3%
Missing	2 1.7%	0 0%	2 1.7%	0 0%
Any Improvement	70 59.8%	70 59.3%	80 68.4%	72 61.5%
No Change	16 13.7%	15 12.7%	8 6.8%	13 11.1%
Any Worsening	4 3.4%	6 5.1%	5 4.3%	3 2.6%
Missing	1 0.9%	0 0%	2 1.7%	1 0.9%
Any Improvement	67 57.3%	69 58.5%	80 68.4%	73 62.4%
No Change	19 16.2%	12 10.2%	7 6%	9 7.7%
Any Worsening	2 1.7%	8 6.8%	4 3.4%	4 3.4%
Missing	1 0.9%	0 0%	2 1.7%	1 0.9%
Any Improvement	66 56.4%	64 54.2%	76 65%	64 54.7%
No Change	14 12%	18 15.3%	6 5.1%	13 11.1%
Any Worsening	6 5.1%	1 0.8%	5 4.3%	4 3.4%
Missing	2 1.7%	6 5.1%	3 2.6%	4 3.4%

48. Secondary Outcome

Title	DBPC Period: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 4, 8, 12, 16, 24, 32, 40 and 52
Description	The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assess self reported fatigue and its impact upon daily activities and function. It uses a 5-point Likert-type scale (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; 4 = very much). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse possible score) to 52 (best score). A higher score reflected an improvement in the participant's health status.
Time Frame	Baseline, Week 4, 8, 12, 16, 24, 32, 40, and 52

Outcome Measure Data

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
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.
Measure Participants	110	114	112	113
Week 4	3 (8.0)	2 (7.8)	4 (9.1)	3 (7.7)
Week 8	3 (8.7)	3 (8.3)	3 (9.1)	5 (8.2)
Week 12	3 (10.0)	4 (9.7)	3 (9.7)	4 (8.1)
Week 16	4 (9.8)	3 (9.8)	4 (10.2)	3 (8.4)
Week 24	3 (9.9)	4 (8.5)	5 (10.3)	3 (7.5)
Week 32	4 (9.6)	4 (9.5)	5 (9.7)	4 (6.8)
Week 40	4 (8.8)	3 (8.6)	6 (9.9)	4 (8.5)
Week 52	4 (9.9)	4 (7.9)	5 (9.7)	5 (8.7)

49. Secondary Outcome

Title	DBPC Period: Number of Participants With Change From Baseline in Prednisone Equivalent Corticosteroid (CS) Dose by >=25% to a Dose of <=7.5 Milligram Per Day (mg/Day), With no BILAG A or 2B Flare in Disease Activity at Week 52
Description	BILAG A or 2B flare is defined as at least one BILAG A grade or two BILAG B 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 period. BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to systemic lupus erythematosus (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	Baseline and Week 52

Outcome Measure Data

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
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.
Measure Participants	68	68	70	71
Count of Participants [Participants]	19 16.2%	23 19.5%	20 17.1%	21 17.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Rate difference
	Estimated Value	5.9
	Confidence Interval	(2-Sided) 95%; -9.7 to 21.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Rate Difference
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; -14.5 to 15.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Rate difference
	Estimated Value	1.6
	Confidence Interval	(2-Sided) 95%; -13.5 to 16.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

50. Secondary Outcome

Title	DBPC Period: Change From Baseline to Week 52 in Prednisone Equivalent Corticosteroid (CS) Daily Dose at at Week 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Description	Change From Baseline in Prednisone-equivalent CS Daily Dose at Week 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 were reported.
Time Frame	Baseline, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Outcome Measure Data

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 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
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.
Measure Participants	113	113	116	114
Week 1	0.21 (1.443)	0.00 (0.000)	0.00 (0.000)	0.00 (0.000)
Week 2	0.10 (1.206)	-0.07 (0.524)	0.00 (0.000)	-0.13 (1.405)
Week 4	0.01 (1.267)	-0.45 (2.879)	-0.04 (0.739)	-0.15 (1.428)
Week 6	-1.07 (3.563)	-0.64 (3.275)	-0.59 (2.095)	-0.70 (3.484)
Week 8	-0.57 (2.588)	-1.24 (3.915)	-1.09 (3.640)	-1.02 (3.422)
Week 10	-1.43 (3.985)	-2.04 (5.146)	-1.56 (4.137)	-2.50 (4.971)
Week 12	-1.26 (3.260)	-1.85 (4.158)	-1.73 (4.574)	-1.97 (4.150)
Week 14	-2.00 (4.569)	-2.70 (5.428)	-1.87 (4.489)	-2.76 (5.125)
Week 16	-1.67 (4.427)	-2.70 (4.955)	-2.47 (5.365)	-2.40 (4.535)
Week 20	-1.94 (4.054)	-2.82 (4.905)	-2.64 (5.489)	-2.53 (4.727)
Week 24	-1.99 (4.228)	-2.64 (5.066)	-2.61 (5.568)	-2.34 (5.330)
Week 28	-2.23 (4.439)	-2.97 (4.981)	-3.07 (6.068)	-2.46 (5.371)
Week 32	-2.45 (4.584)	-3.13 (5.193)	-3.18 (6.161)	-2.44 (5.347)
Week 36	-2.42 (4.835)	-3.31 (5.327)	-3.18 (6.136)	-2.37 (5.445)
Week 40	-2.08 (6.149)	-3.21 (5.280)	-3.24 (6.218)	-2.67 (5.202)
Week 44	-2.42 (4.833)	-3.21 (5.280)	-3.27 (6.254)	-2.56 (5.121)
Week 48	-2.38 (4.895)	-3.22 (5.310)	-3.37 (6.265)	-2.62 (5.136)
Week 52	-1.70 (5.470)	-2.94 (5.534)	-3.09 (5.981)	-2.63 (5.673)

51. Secondary Outcome

Title	DBPC Period: Number of Participants With Reduction From Baseline in Prednisone Equivalent Corticosteroid (CS) Daily Dose by > 0 to 25%, >25% to 50%, >50% to 100% or an Increase at Week 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Description	Number of Participants With Reduction From Baseline in Prednisone-equivalent Corticosteroid (CS) Daily Dose by > 0 to 25%, >25% to 50%, >50% to 100% or an Increase at Week 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 were reported.
Time Frame	Baseline, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Outcome Measure Data

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
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.
Measure Participants	114	115	116	114
Reduction of dose by >0-25% Week 1	0 0%	0 0%	0 0%	0 0%
Reduction of dose by >0-25% Week 2	1 0.9%	2 1.7%	0 0%	0 0%
Reduction of dose by >0-25% Week 4	1 0.9%	5 4.2%	2 1.7%	1 0.9%
Reduction of dose by >0-25% Week 6	3 2.6%	4 3.4%	3 2.6%	4 3.4%
Reduction of dose by >0-25% Week 8	6 5.1%	6 5.1%	5 4.3%	6 5.1%
Reduction of dose by >0-25% Week 10	0 0%	3 2.5%	4 3.4%	5 4.3%
Reduction of dose by >0-25% Week 12	5 4.3%	11 9.3%	8 6.8%	6 5.1%
Reduction of dose by >0-25% Week 14	2 1.7%	2 1.7%	4 3.4%	5 4.3%
Reduction of dose by >0-25% Week 16	5 4.3%	10 8.5%	5 4.3%	6 5.1%
Reduction of dose by >0-25% Week 20	5 4.3%	10 8.5%	5 4.3%	5 4.3%
Reduction of dose by >0-25% Week 24	4 3.4%	10 8.5%	5 4.3%	5 4.3%
Reduction of dose by >0-25% Week 28	2 1.7%	8 6.8%	5 4.3%	4 3.4%
Reduction of dose by >0-25% Week 32	1 0.9%	7 5.9%	4 3.4%	3 2.6%
Reduction of dose by >0-25% Week 36	1 0.9%	5 4.2%	4 3.4%	3 2.6%
Reduction of dose by >0-25% Week 40	1 0.9%	5 4.2%	3 2.6%	3 2.6%
Reduction of dose by >0-25% Week 44	1 0.9%	5 4.2%	3 2.6%	3 2.6%
Reduction of dose by >0-25% Week 48	0 0%	5 4.2%	4 3.4%	3 2.6%
Reduction of dose by >0-25% Week 52	1 0.9%	5 4.2%	4 3.4%	4 3.4%
Reduction of dose by >25- 50% Week 1	0 0%	0 0%	0 0%	0 0%
Reduction of dose by >25- 50% Week 2	0 0%	0 0%	0 0%	0 0%
Reduction of dose by >25- 50% Week 4	1 0.9%	2 1.7%	1 0.9%	0 0%
Reduction of dose by >25- 50% Week 6	4 3.4%	1 0.8%	2 1.7%	0 0%
Reduction of dose by >25- 50% Week 8	5 4.3%	9 7.6%	6 5.1%	5 4.3%
Reduction of dose by >25- 50% Week 10	7 6%	6 5.1%	4 3.4%	10 8.5%
Reduction of dose by >25- 50% Week 12	14 12%	9 7.6%	10 8.5%	15 12.8%
Reduction of dose by >25- 50% Week 14	7 6%	6 5.1%	2 1.7%	8 6.8%
Reduction of dose by >25- 50% Week 16	16 13.7%	12 10.2%	9 7.7%	16 13.7%
Reduction of dose by >25- 50% Week 20	13 11.1%	11 9.3%	8 6.8%	14 12%
Reduction of dose by >25- 50% Week 24	12 10.3%	9 7.6%	8 6.8%	13 11.1%
Reduction of dose by >25- 50% Week 28	14 12%	12 10.2%	9 7.7%	16 13.7%
Reduction of dose by >25- 50% Week 32	15 12.8%	11 9.3%	8 6.8%	16 13.7%
Reduction of dose by >25- 50% Week 36	15 12.8%	13 11%	6 5.1%	15 12.8%
Reduction of dose by >25- 50% Week 40	15 12.8%	15 12.7%	6 5.1%	16 13.7%
Reduction of dose by >25- 50% Week 44	15 12.8%	15 12.7%	6 5.1%	16 13.7%
Reduction of dose by >25- 50% Week 48	15 12.8%	14 11.9%	6 5.1%	17 14.5%
Reduction of dose by >25- 50% Week 52	16 13.7%	12 10.2%	7 6%	17 14.5%
Reduction of dose by >50-100% Week 1	0 0%	0 0%	0 0%	0 0%
Reduction of dose by >50-100% Week 2	0 0%	0 0%	0 0%	1 0.9%
Reduction of dose by >50-100% Week 4	0 0%	1 0.8%	0 0%	1 0.9%
Reduction of dose by >50-100% Week 6	1 0.9%	1 0.8%	0 0%	1 0.9%
Reduction of dose by >50-100% Week 8	1 0.9%	3 2.5%	4 3.4%	3 2.6%
Reduction of dose by >50-100% Week 10	2 1.7%	3 2.5%	3 2.6%	4 3.4%
Reduction of dose by >50-100% Week 12	1 0.9%	6 5.1%	6 5.1%	6 5.1%
Reduction of dose by >50-100% Week 14	5 4.3%	6 5.1%	7 6%	7 6%
Reduction of dose by >50-100% Week 16	5 4.3%	13 11%	13 11.1%	9 7.7%
Reduction of dose by >50-100% Week 20	7 6%	13 11%	14 12%	11 9.4%
Reduction of dose by >50-100% Week 24	7 6%	14 11.9%	13 11.1%	11 9.4%
Reduction of dose by >50-100% Week 28	9 7.7%	14 11.9%	15 12.8%	11 9.4%
Reduction of dose by >50-100% Week 32	11 9.4%	16 13.6%	16 13.7%	12 10.3%
Reduction of dose by >50-100% Week 36	10 8.5%	17 14.4%	18 15.4%	11 9.4%
Reduction of dose by >50-100% Week 40	10 8.5%	15 12.7%	18 15.4%	11 9.4%
Reduction of dose by >50-100% Week 44	10 8.5%	15 12.7%	18 15.4%	10 8.5%
Reduction of dose by >50-100% Week 48	9 7.7%	15 12.7%	19 16.2%	10 8.5%
Reduction of dose by >50-100% Week 52	9 7.7%	17 14.4%	19 16.2%	12 10.3%
Increased from Baseline Week 1	1 0.9%	0 0%	0 0%	0 0%
Increased from Baseline Week 2	2 1.7%	0 0%	0 0%	0 0%
Increased from Baseline Week 4	2 1.7%	1 0.8%	1 0.9%	0 0%
Increased from Baseline Week 6	1 0.9%	1 0.8%	0 0%	0 0%
Increased from Baseline Week 8	2 1.7%	1 0.8%	1 0.9%	0 0%
Increased from Baseline Week 10	1 0.9%	1 0.8%	0 0%	0 0%
Increased from Baseline Week 12	1 0.9%	1 0.8%	1 0.9%	0 0%
Increased from Baseline Week 14	1 0.9%	0 0%	0 0%	0 0%
Increased from Baseline Week 16	1 0.9%	1 0.8%	1 0.9%	0 0%
Increased from Baseline Week 20	0 0%	0 0%	0 0%	0 0%
Increased from Baseline Week 24	0 0%	0 0%	0 0%	0 0%
Increased from Baseline Week 28	0 0%	0 0%	0 0%	1 0.9%
Increased from Baseline Week 32	0 0%	0 0%	0 0%	1 0.9%
Increased from Baseline Week 36	0 0%	0 0%	0 0%	1 0.9%
Increased from Baseline Week 40	1 0.9%	0 0%	0 0%	1 0.9%
Increased from Baseline Week 44	0 0%	0 0%	0 0%	1 0.9%
Increased from Baseline Week 48	0 0%	0 0%	0 0%	1 0.9%
Increased from Baseline Week 52	2 1.7%	0 0%	0 0%	2 1.7%

52. Secondary Outcome

Title	DBPC Period: Cumulative Prednisone Equivalent Corticosteroid (CS) Dose at Week 52
Description	Cumulative Prednisone-equivalent Corticosteroid (CS) Dose was calculated at Week 52.
Time Frame	Week 52

Outcome Measure Data

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
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.
Measure Participants	114	115	116	114
Mean (Standard Deviation) [Milligrams]	2267.66 (1507.652)	2209.46 (1922.557)	2137.70 (1618.688)	2205.56 (1737.092)

53. Secondary Outcome

Title	DBPC Period: Number of Participants With a Sustained Reduction of Oral Corticosteroids (OCS) Dose to 7.5 mg Prednisone Equivalent Per Day or Less With Response Based on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Week 52
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

Outcome Measure Data

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
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.
Measure Participants	56	59	63	57
Count of Participants [Participants]	43 36.8%	45 38.1%	43 36.8%	41 35%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7728
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.14
	Confidence Interval	(2-Sided) 95%; 0.46 to 2.82
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3314
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.66
	Confidence Interval	(2-Sided) 95%; 0.28 to 1.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7205
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.36 to 2.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

54. Secondary Outcome

Title	DBPC Period: Number of Participants With a Sustained Reduction of Oral Corticosteroids (OCS) Dose to 7.5 mg Prednisone Equivalent Per Day or Less With Response Based on Systemic Lupus Erythematosus Responder Index 6 (SRI-6) at Week 52
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

Outcome Measure Data

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 (HDA participants) and 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
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.
Measure Participants	27	28	35	24
Count of Participants [Participants]	18 15.4%	19 16.1%	23 19.7%	15 12.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8364
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.13
	Confidence Interval	(2-Sided) 95%; 0.35 to 3.71
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8287
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.13
	Confidence Interval	(2-Sided) 95%; 0.37 to 3.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7621
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.21
	Confidence Interval	(2-Sided) 95%; 0.35 to 4.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

55. Secondary Outcome

Title	DBPC Period: Number of Participants With a Sustained Reduction of Oral Corticosteroids (OCS) Dose to 7.5 mg Prednisone Equivalent Per Day or Less With Response Based on SRI-4 at Week 52 in Serologically Active Subgroup
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 very well(0)-very poor(100).
Time Frame	Week 52

Outcome Measure Data

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 antidsDNA and/or low complement levels at screening (Serologically active subgroup) and 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
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.
Measure Participants	26	33	32	34
Count of Participants [Participants]	21 17.9%	25 21.2%	22 18.8%	25 21.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8464
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95%; 0.23 to 3.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4170
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.59
	Confidence Interval	(2-Sided) 95%; 0.16 to 2.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9988
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.27 to 3.74
	Parameter Dispersion	Type: Value:
	Estimation Comments

56. Secondary Outcome

Title	DBPC Period: Number of Participants With Lupus Low Disease Activity State (LLDAS) at Week 52
Description	Lupus low disease activity state will be measured as: SLEDAI-2K <= 4; No activity in any major organ systems (renal, central nervous system, cardiopulmonary, vasculitis, fever); No new features of disease activity compared with the previous assessment; Prednisone-equivalent <= 7.5 milligram per day; Unchanged background immunosuppressive therapy.
Time Frame	Week 52

Outcome Measure Data

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
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.
Measure Participants	114	115	116	114
Count of Participants [Participants]	29 24.8%	32 27.1%	35 29.9%	29 24.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6970
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.13
	Confidence Interval	(2-Sided) 95%; 0.62 to 2.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3234
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.34
	Confidence Interval	(2-Sided) 95%; 0.75 to 2.42
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9846
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.54 to 1.82
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Double-Blind Placebo-Controlled: Baseline up to Week 56 Long-Term Extension: Up to Week 108
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
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.
All Cause Mortality
	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
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/117 (0%)		1/118 (0.8%)		1/117 (0.9%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Serious Adverse Events
	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
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/117 (8.5%)		13/118 (11%)		11/117 (9.4%)		9/117 (7.7%)		5/62 (8.1%)		5/69 (7.2%)		5/80 (6.3%)		7/72 (9.7%)
Blood and lymphatic system disorders
Bone marrow failure	0/117 (0%)		0/118 (0%)		1/117 (0.9%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Pancytopenia	0/117 (0%)		0/118 (0%)		0/117 (0%)		1/117 (0.9%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Anaemia	0/117 (0%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		1/62 (1.6%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Leukopenia	0/117 (0%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		1/80 (1.3%)		0/72 (0%)
Lymphadenitis	0/117 (0%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		1/62 (1.6%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Thrombocytopenia	0/117 (0%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		1/62 (1.6%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Cardiac disorders
Pericarditis lupus	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Ear and labyrinth disorders
Vertigo	1/117 (0.9%)		0/118 (0%)		1/117 (0.9%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Eye disorders
Cataract	0/117 (0%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		1/72 (1.4%)
Gastrointestinal disorders
Abdominal pain	0/117 (0%)		0/118 (0%)		1/117 (0.9%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Ascites	0/117 (0%)		0/118 (0%)		0/117 (0%)		1/117 (0.9%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Colitis	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Lupus enteritis	0/117 (0%)		0/118 (0%)		0/117 (0%)		1/117 (0.9%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Pancreatitis	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Dental cyst	1/117 (0.9%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Diarrhoea	1/117 (0.9%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Abdominal adhesions	0/117 (0%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		1/72 (1.4%)
General disorders
Non-cardiac chest pain	0/117 (0%)		2/118 (1.7%)		0/117 (0%)		2/117 (1.7%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Chest pain	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Hepatobiliary disorders
Cholelithiasis	0/117 (0%)		0/118 (0%)		0/117 (0%)		1/117 (0.9%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		1/72 (1.4%)
Hepatitis	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/117 (0%)		1/62 (1.6%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Infections and infestations
Otitis media	0/117 (0%)		0/118 (0%)		2/117 (1.7%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Campylobacter sepsis	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Cellulitis	0/117 (0%)		0/118 (0%)		0/117 (0%)		1/117 (0.9%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Clostridium difficile infection	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Diverticulitis	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Gastroenteritis	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Giardiasis	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Pneumonia	0/117 (0%)		0/118 (0%)		0/117 (0%)		1/117 (0.9%)		0/62 (0%)		0/69 (0%)		1/80 (1.3%)		1/72 (1.4%)
Pyelonephritis acute	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Soft tissue infection	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Upper respiratory tract infection	0/117 (0%)		0/118 (0%)		1/117 (0.9%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Herpes zoster	1/117 (0.9%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Osteomyelitis	1/117 (0.9%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		1/62 (1.6%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Urinary tract infection	0/117 (0%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		2/69 (2.9%)		0/80 (0%)		0/72 (0%)
Appendicitis	0/117 (0%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		1/72 (1.4%)
Bronchitis	0/117 (0%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		1/80 (1.3%)		0/72 (0%)
Pneumonia mycoplasmal	0/117 (0%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		1/72 (1.4%)
Subperiosteal abscess	0/117 (0%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		1/62 (1.6%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Injury, poisoning and procedural complications
Ligament injury	0/117 (0%)		0/118 (0%)		0/117 (0%)		1/117 (0.9%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Post procedural complication	0/117 (0%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		1/72 (1.4%)
Post procedural haemorrhage	0/117 (0%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		1/72 (1.4%)
Wound	0/117 (0%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		1/72 (1.4%)
Investigations
Liver function test increased	0/117 (0%)		0/118 (0%)		1/117 (0.9%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Transaminases increased	0/117 (0%)		0/118 (0%)		0/117 (0%)		1/117 (0.9%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Platelet count decreased	1/117 (0.9%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Metabolism and nutrition disorders
Hypoglycaemia	0/117 (0%)		0/118 (0%)		1/117 (0.9%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Back pain	0/117 (0%)		0/118 (0%)		1/117 (0.9%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Intervertebral disc protrusion	0/117 (0%)		0/118 (0%)		1/117 (0.9%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Musculoskeletal chest pain	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Osteoarthritis	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Osteonecrosis	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		1/72 (1.4%)
Systemic lupus erythematosus	0/117 (0%)		0/118 (0%)		0/117 (0%)		1/117 (0.9%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Osteonecrosis of jaw	1/117 (0.9%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		1/62 (1.6%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
SLE arthritis	1/117 (0.9%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Papillary thyroid cancer	1/117 (0.9%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Basal cell carcinoma	0/117 (0%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		1/62 (1.6%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Nervous system disorders
Dizziness	0/117 (0%)		0/118 (0%)		1/117 (0.9%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		1/80 (1.3%)		0/72 (0%)
Headache	2/117 (1.7%)		1/118 (0.8%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Presyncope	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Syncope	0/117 (0%)		0/118 (0%)		1/117 (0.9%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Ischaemic stroke	1/117 (0.9%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Cerebral infarction	0/117 (0%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		1/62 (1.6%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Cerebral venous sinus thrombosis	0/117 (0%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		1/62 (1.6%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Renal and urinary disorders
Acute kidney injury	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Lupus nephritis	0/117 (0%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		1/62 (1.6%)		1/69 (1.4%)		0/80 (0%)		0/72 (0%)
Urinary retention	0/117 (0%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		1/80 (1.3%)		0/72 (0%)
Reproductive system and breast disorders
Pelvic pain	0/117 (0%)		0/118 (0%)		1/117 (0.9%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Uterine polyp	1/117 (0.9%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		1/69 (1.4%)		0/80 (0%)		0/72 (0%)
Metrorrhagia	0/117 (0%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		1/69 (1.4%)		0/80 (0%)		0/72 (0%)
Ovarian cyst	0/117 (0%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		1/80 (1.3%)		0/72 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/117 (0%)		0/118 (0%)		0/117 (0%)		1/117 (0.9%)		0/62 (0%)		0/69 (0%)		1/80 (1.3%)		0/72 (0%)
Skin and subcutaneous tissue disorders
Cutaneous vasculitis	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Dermatosis	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Dermatitis contact	0/117 (0%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		1/72 (1.4%)
Urticaria	0/117 (0%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		1/69 (1.4%)		0/80 (0%)		0/72 (0%)
Vascular disorders
Hypertension	0/117 (0%)		0/118 (0%)		1/117 (0.9%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Malignant hypertension	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Hypotension	0/117 (0%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		1/80 (1.3%)		0/72 (0%)
Hypovolaemic shock	0/117 (0%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		1/72 (1.4%)
Other (Not Including Serious) Adverse Events
	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
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	76/117 (65%)		85/118 (72%)		75/117 (64.1%)		78/117 (66.7%)		22/62 (35.5%)		34/69 (49.3%)		35/80 (43.8%)		23/72 (31.9%)
Blood and lymphatic system disorders
Lymphopenia	9/117 (7.7%)		4/118 (3.4%)		6/117 (5.1%)		2/117 (1.7%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Neutropenia	4/117 (3.4%)		1/118 (0.8%)		2/117 (1.7%)		6/117 (5.1%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Gastrointestinal disorders
Diarrhoea	11/117 (9.4%)		12/118 (10.2%)		17/117 (14.5%)		10/117 (8.5%)		3/62 (4.8%)		5/69 (7.2%)		7/80 (8.8%)		2/72 (2.8%)
Nausea	7/117 (6%)		8/118 (6.8%)		9/117 (7.7%)		5/117 (4.3%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Vomiting	4/117 (3.4%)		9/118 (7.6%)		8/117 (6.8%)		3/117 (2.6%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Abdominal pain upper	5/117 (4.3%)		6/118 (5.1%)		8/117 (6.8%)		5/117 (4.3%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Abdominal pain	3/117 (2.6%)		7/118 (5.9%)		3/117 (2.6%)		5/117 (4.3%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Gastritis	3/117 (2.6%)		6/118 (5.1%)		3/117 (2.6%)		4/117 (3.4%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
General disorders
Influenza like illness	5/117 (4.3%)		7/118 (5.9%)		9/117 (7.7%)		7/117 (6%)		4/62 (6.5%)		0/69 (0%)		2/80 (2.5%)		0/72 (0%)
Infections and infestations
Urinary tract infection	16/117 (13.7%)		21/118 (17.8%)		26/117 (22.2%)		21/117 (17.9%)		4/62 (6.5%)		7/69 (10.1%)		7/80 (8.8%)		6/72 (8.3%)
Nasopharyngitis	8/117 (6.8%)		13/118 (11%)		15/117 (12.8%)		7/117 (6%)		5/62 (8.1%)		5/69 (7.2%)		7/80 (8.8%)		5/72 (6.9%)
Upper respiratory tract infection	12/117 (10.3%)		15/118 (12.7%)		6/117 (5.1%)		8/117 (6.8%)		3/62 (4.8%)		6/69 (8.7%)		3/80 (3.8%)		0/72 (0%)
Pharyngitis	8/117 (6.8%)		5/118 (4.2%)		4/117 (3.4%)		4/117 (3.4%)		0/62 (0%)		3/69 (4.3%)		6/80 (7.5%)		1/72 (1.4%)
Gastroenteritis	6/117 (5.1%)		4/118 (3.4%)		2/117 (1.7%)		2/117 (1.7%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Herpes zoster	2/117 (1.7%)		2/118 (1.7%)		6/117 (5.1%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Bronchitis	0/117 (0%)		0/118 (0%)		0/117 (0%)		0/117 (0%)		0/62 (0%)		4/69 (5.8%)		5/80 (6.3%)		3/72 (4.2%)
Investigations
Alanine aminotransferase increased	3/117 (2.6%)		8/118 (6.8%)		6/117 (5.1%)		6/117 (5.1%)		5/62 (8.1%)		4/69 (5.8%)		1/80 (1.3%)		2/72 (2.8%)
Lipase increased	2/117 (1.7%)		4/118 (3.4%)		6/117 (5.1%)		6/117 (5.1%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Aspartate aminotransferase increased	3/117 (2.6%)		8/118 (6.8%)		3/117 (2.6%)		4/117 (3.4%)		3/62 (4.8%)		4/69 (5.8%)		1/80 (1.3%)		2/72 (2.8%)
Gamma-glutamyltransferase increased	6/117 (5.1%)		4/118 (3.4%)		4/117 (3.4%)		7/117 (6%)		3/62 (4.8%)		3/69 (4.3%)		1/80 (1.3%)		4/72 (5.6%)
Amylase increased	5/117 (4.3%)		2/118 (1.7%)		4/117 (3.4%)		8/117 (6.8%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Transaminases increased	3/117 (2.6%)		3/118 (2.5%)		3/117 (2.6%)		6/117 (5.1%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Musculoskeletal and connective tissue disorders
Back Pain	3/117 (2.6%)		4/118 (3.4%)		5/117 (4.3%)		9/117 (7.7%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Nervous system disorders
Headache	20/117 (17.1%)		17/118 (14.4%)		19/117 (16.2%)		17/117 (14.5%)		1/62 (1.6%)		7/69 (10.1%)		2/80 (2.5%)		5/72 (6.9%)
Dizziness	3/117 (2.6%)		5/118 (4.2%)		4/117 (3.4%)		6/117 (5.1%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	6/117 (5.1%)		2/118 (1.7%)		1/117 (0.9%)		0/117 (0%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)
Vascular disorders
Hypertension	0/117 (0%)		6/118 (5.1%)		4/117 (3.4%)		1/117 (0.9%)		0/62 (0%)		0/69 (0%)		0/80 (0%)		0/72 (0%)

Limitations/Caveats

Primary and Secondary endpoints were planned to be analyze only for Double-Blind Placebo-controlled period.

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Certain Agreements

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