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A Phase 2 Study to Evaluate the Safety and Efficacy of LOU064 in Patients With Moderate to Severe Sjögren's Syndrome (LOUiSSe)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04035668
Recruitment Status : Terminated (Sponsor's decision)
First Posted : July 29, 2019
Results First Posted : December 20, 2022
Last Update Posted : January 30, 2023
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Other
Condition Sjögren Syndrome
Interventions Drug: Remibrutinib
Drug: Placebo
Enrollment 73
Recruitment Details Participants took part in 26 investigative sites in 12 countries.
Pre-assignment Details The screening period of up to 6 weeks began after the subject had provided written informed consent. Eligible subjects were randomized in a 1:1:1 ratio to one of the 3 treatment groups.
Arm/Group Title Remibrutinib 100 mg Bid Remibrutinib 100 mg qd Placebo
Hide Arm/Group Description Remibrutinib 100 mg twice daily (bid) Remibrutinib 100 mg once daily (qd) Placebo group
Period Title: Overall Study
Started 24 25 24
Completed 17 17 21
Not Completed 7 8 3
Reason Not Completed
Adverse Event             3             4             2
Lost to Follow-up             0             1             0
Physician Decision             2             1             1
Subject Decision             2             2             0
Arm/Group Title Remibrutinib 100 mg Bid Remibrutinib 100 mg qd Placebo Total
Hide Arm/Group Description Remibrutinib 100 mg twice daily (bid) Remibrutinib 100 mg once daily (qd) Placebo group Total of all reporting groups
Overall Number of Baseline Participants 24 25 24 73
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 24 participants 25 participants 24 participants 73 participants
49.5  (15.21) 54.8  (10.51) 51.0  (13.94) 51.8  (13.34)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 25 participants 24 participants 73 participants
Female
24
 100.0%
24
  96.0%
23
  95.8%
71
  97.3%
Male
0
   0.0%
1
   4.0%
1
   4.2%
2
   2.7%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 25 participants 24 participants 73 participants
Asian
7
  29.2%
7
  28.0%
7
  29.2%
21
  28.8%
White
17
  70.8%
17
  68.0%
16
  66.7%
50
  68.5%
Unknown
0
   0.0%
1
   4.0%
0
   0.0%
1
   1.4%
Black or African American
0
   0.0%
0
   0.0%
1
   4.2%
1
   1.4%
1.Primary Outcome
Title Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) Total Score at Week 24
Hide Description

ESSDAI is a validated disease outcome measure for Sjögren's Syndrome. The instrument contains 12 organ-specific domains contributing to disease activity: constitutional, lymphadenopathy, glandular, articular, cutaneous, pulmonary, renal, muscular, peripheral nervous system, central nervous system, hematological and biological. For each domain, features of disease activity were scored according to their severity. These scores were summed across the 12 domains in a weighted manner to provide the total score. ESSDAI total score ranges from 0 to 123 with higher values indicating more disease activity. A negative change from baseline indicates improvement.

The baseline value is defined as the last assessment performed prior to administration of the first dose of study treatment.

A mixed effect model for repeated measurements (MMRM) was fitted to the changes from baseline in ESSDAI for all post-baseline time points up to Week 24. Values estimated from the model are presented in this table.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set (FAS) with a valid assessment for the outcome measure. FAS included all participants who were randomized in the study.
Arm/Group Title Remibrutinib 100 mg qd Remibrutinib 100 mg Bid Any Remibrutinib Placebo
Hide Arm/Group Description:
Remibrutinib 100 mg once daily (qd)
Remibrutinib 100 mg twice daily (bid)
Patients in any of the two remibrutinib treatment groups
Placebo group
Overall Number of Participants Analyzed 24 24 48 24
Least Squares Mean (Standard Error)
Unit of Measure: score on scale
-4.70  (0.78) -3.70  (0.80) -4.20  (0.56) -1.34  (0.74)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.86
Confidence Interval (2-Sided) 95%
-4.71 to -1.01
Estimation Comments Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.00
Confidence Interval (2-Sided) 95%
-3.24 to 1.25
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
2.Secondary Outcome
Title Change From Baseline in ESSDAI Total Score Over Time
Hide Description

ESSDAI is a validated disease outcome measure for Sjögren's Syndrome. The instrument contains 12 organ-specific domains contributing to disease activity: constitutional, lymphadenopathy, glandular, articular, cutaneous, pulmonary, renal, muscular, peripheral nervous system, central nervous system, hematological and biological. For each domain, features of disease activity were scored according to their severity. These scores were summed across the 12 domains in a weighted manner to provide the total score. ESSDAI total score ranges from 0 to 123 with higher values indicating more disease activity. A negative change from baseline indicates improvement.

The baseline value is defined as the last assessment performed prior to administration of the first dose of study treatment.

A mixed effect model for repeated measurements (MMRM) was fitted to the changes from baseline in ESSDAI for all post-baseline time points up to Week 24. Values estimated from the model are presented in this table.
Time Frame Baseline, Week 2, Week 4, Week 8, Week 12, Week 16 and Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set (FAS) with a valid assessment for the outcome measure. FAS included all participants who were randomized in the study.
Arm/Group Title Remibrutinib 100 mg qd Remibrutinib 100 mg Bid Any Remibrutinib Placebo
Hide Arm/Group Description:
Remibrutinib 100 mg once daily (qd)
Remibrutinib 100 mg twice daily (bid)
Patients in any of the two remibrutinib treatment groups
Placebo group
Overall Number of Participants Analyzed 24 24 48 24
Least Squares Mean (Standard Error)
Unit of Measure: score on scale
Week 2 -1.68  (0.52) -1.05  (0.52) -1.37  (0.37) -0.37  (0.55)
Week 4 -2.57  (0.60) -2.54  (0.62) -2.55  (0.43) -0.79  (0.61)
Week 8 -2.74  (0.72) -2.93  (0.71) -2.83  (0.51) -2.36  (0.69)
Week 12 -3.66  (0.74) -2.56  (0.75) -3.11  (0.53) -1.92  (0.73)
Week 16 -4.02  (0.71) -2.57  (0.74) -3.29  (0.51) -2.16  (0.69)
Week 20 -4.40  (0.73) -3.26  (0.75) -3.83  (0.52) -1.84  (0.69)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.065
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.99
Confidence Interval (2-Sided) 95%
-2.29 to 0.30
Estimation Comments Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.010
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.76
Confidence Interval (2-Sided) 95%
-3.24 to -0.29
Estimation Comments Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.289
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.47
Confidence Interval (2-Sided) 95%
-2.17 to 1.22
Estimation Comments Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.093
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.19
Confidence Interval (2-Sided) 95%
-2.97 to 0.59
Estimation Comments Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.094
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.13
Confidence Interval (2-Sided) 95%
-2.84 to 0.57
Estimation Comments Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 20
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.012
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.99
Confidence Interval (2-Sided) 95%
-3.71 to -0.28
Estimation Comments [Not Specified]
Other Statistical Analysis Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 2
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.63
Confidence Interval (2-Sided) 95%
-2.10 to 0.84
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 4
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.03
Confidence Interval (2-Sided) 95%
-1.75 to 1.69
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 8
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.19
Confidence Interval (2-Sided) 95%
-1.83 to 2.21
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 12
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.10
Confidence Interval (2-Sided) 95%
-3.20 to 1.01
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 16
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.45
Confidence Interval (2-Sided) 95%
-3.50 to 0.60
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 20
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.14
Confidence Interval (2-Sided) 95%
-3.22 to 0.95
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
3.Secondary Outcome
Title Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) Total Score Over Time
Hide Description

ESSPRI is an established disease outcome measure for Sjögren's Syndrome. It consists of three domains of dryness, pain, and fatigue. The patient can assess the severity of symptoms they experience on a single 0-10 numerical scale for each of the three domains. The ESSPRI score is defined as the mean of scores from the three scales: (dryness + pain +fatigue) /3. ESSPRI total score ranges from 0 to 10 with higher values indicating more disease symptoms. A negative change from baseline indicates improvement.

The baseline value is defined as the last assessment performed prior to administration of the first dose of study treatment.

A mixed effect model for repeated measurements (MMRM) was fitted to the changes from baseline in ESSPRI for all post-baseline time points up to Week 24. Values estimated from the model are presented in this table.
Time Frame Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20 and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set (FAS) with a valid assessment for the outcome measure. FAS included all participants who were randomized in the study.
Arm/Group Title Remibrutinib 100 mg qd Remibrutinib 100 mg Bid Any Remibrutinib Placebo
Hide Arm/Group Description:
Remibrutinib 100 mg once daily (qd)
Remibrutinib 100 mg twice daily (bid)
Patients in any of the two remibrutinib treatment groups
Placebo group
Overall Number of Participants Analyzed 24 24 48 24
Least Squares Mean (Standard Error)
Unit of Measure: score on scale
Week 2 -0.44  (0.26) 0.18  (0.26) -0.13  (0.18) -0.09  (0.27)
Week 4 -0.72  (0.30) -0.14  (0.30) -0.43  (0.21) -0.35  (0.30)
Week 8 -0.83  (0.31) -0.38  (0.31) -0.60  (0.22) -0.57  (0.29)
Week 12 -0.88  (0.31) -0.32  (0.31) -0.60  (0.22) -0.66  (0.29)
Week 16 -0.77  (0.36) -0.39  (0.37) -0.58  (0.26) -0.71  (0.34)
Week 20 -0.92  (0.38) -0.74  (0.39) -0.83  (0.27) -0.92  (0.36)
Week 24 -1.17  (0.34) -0.76  (0.35) -0.96  (0.24) -1.13  (0.31)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.460
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.03
Confidence Interval (2-Sided) 95%
-0.69 to 0.62
Estimation Comments Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.418
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.08
Confidence Interval (2-Sided) 95%
-0.82 to 0.66
Estimation Comments Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.466
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.03
Confidence Interval (2-Sided) 95%
-0.76 to 0.70
Estimation Comments Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.560
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-0.67 to 0.79
Estimation Comments Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.616
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.13
Confidence Interval (2-Sided) 95%
-0.73 to 0.99
Estimation Comments Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 20
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.581
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.13
Confidence Interval (2-Sided) 95%
-0.81 to 0.99
Estimation Comments [Not Specified]
Other Statistical Analysis Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.663
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.17
Confidence Interval (2-Sided) 95%
-0.62 to 0.96
Estimation Comments Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 2
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.62
Confidence Interval (2-Sided) 95%
-1.35 to 0.11
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 4
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.58
Confidence Interval (2-Sided) 95%
-1.42 to 0.26
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 8
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.45
Confidence Interval (2-Sided) 95%
-1.31 to 0.42
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 12
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.57
Confidence Interval (2-Sided) 95%
-1.44 to 0.31
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 16
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.37
Confidence Interval (2-Sided) 95%
-1.39 to 0.65
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 20
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.37
Confidence Interval (2-Sided) 95%
-1.39 to 0.65
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.40
Confidence Interval (2-Sided) 95%
-1.37 to 0.57
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
4.Secondary Outcome
Title Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) Total Score Over Time
Hide Description

FACIT-F v4 is a short, 13-item, easy-to-administer tool that measures an individual's level of fatigue during their usual daily activities over the past week. The level of fatigue was measured on a 5-point Likert scale (0 = not at all, 1 = a little bit, 2 = somewhat, 3 = quite a bit, 4 = very much). FACIT-F total score ranges from 0 to 52 with higher values indicating higher quality of life (less fatigue). A positive change from baseline is a favorable outcome.

The baseline value is defined as the last assessment performed prior to administration of the first dose of study treatment.

A mixed effect model for repeated measurements (MMRM) was fitted to the changes from baseline in FACIT-F for all post-baseline time points up to Week 24. Values estimated from the model are presented in this table.
Time Frame Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20 and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set (FAS) with a valid assessment for the outcome measure. FAS included all participants who were randomized in the study.
Arm/Group Title Remibrutinib 100 mg qd Remibrutinib 100 mg Bid Any Remibrutinib Placebo
Hide Arm/Group Description:
Remibrutinib 100 mg once daily (qd)
Remibrutinib 100 mg twice daily (bid)
Patients in any of the two remibrutinib treatment groups
Placebo group
Overall Number of Participants Analyzed 24 23 47 23
Least Squares Mean (Standard Error)
Unit of Measure: score on scale
Week 2 1.80  (1.32) -0.51  (1.35) 0.64  (0.95) 3.37  (1.43)
Week 4 4.83  (1.50) 3.97  (1.57) 4.40  (1.09) 3.51  (1.58)
Week 8 4.00  (1.64) 3.79  (1.66) 3.90  (1.17) 5.26  (1.60)
Week 12 4.88  (1.80) 4.25  (1.86) 4.56  (1.30) 7.30  (1.77)
Week 16 4.40  (1.97) 3.29  (2.08) 3.84  (1.44) 7.73  (1.98)
Week 20 10.01  (2.20) 4.32  (2.30) 7.16  (1.60) 5.77  (2.17)
Week 24 8.17  (2.45) 4.64  (2.55) 6.40  (1.77) 7.45  (2.32)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.940
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.73
Confidence Interval (2-Sided) 95%
-6.18 to 0.73
Estimation Comments Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.322
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.89
Confidence Interval (2-Sided) 95%
-2.95 to 4.74
Estimation Comments Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.753
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.36
Confidence Interval (2-Sided) 95%
-5.32 to 2.59
Estimation Comments Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.891
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.74
Confidence Interval (2-Sided) 95%
-7.13 to 1.66
Estimation Comments Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.941
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.88
Confidence Interval (2-Sided) 95%
-8.77 to 1.01
Estimation Comments Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 20
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.304
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.39
Confidence Interval (2-Sided) 95%
-4.01 to 6.79
Estimation Comments [Not Specified]
Other Statistical Analysis Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.640
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.05
Confidence Interval (2-Sided) 95%
-6.89 to 4.79
Estimation Comments Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 2
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.32
Confidence Interval (2-Sided) 95%
-1.44 to 6.07
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 4
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.86
Confidence Interval (2-Sided) 95%
-3.46 to 5.18
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 8
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.20
Confidence Interval (2-Sided) 95%
-4.43 to 4.83
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 12
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.63
Confidence Interval (2-Sided) 95%
-4.53 to 5.78
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 16
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.11
Confidence Interval (2-Sided) 95%
-4.60 to 6.82
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 20
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 5.69
Confidence Interval (2-Sided) 95%
-0.66 to 12.04
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.53
Confidence Interval (2-Sided) 95%
-3.53 to 10.59
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
5.Secondary Outcome
Title Change From Baseline in EuroQual 5 Dimensions (EQ-5D) VAS Score Over Time
Hide Description

EQ-5D is a standardized instrument that measures the health-related quality of life. The EQ-5D consists of a descriptive system and a visual analog scale (VAS).The EQ-5D VAS records the patient's self-rated health on a vertical visual analogue scale with 0 representing 'Worst imaginable Health State' and 100 'Best imaginable Health State'. A positive change from baseline is a favorable outcome.

The baseline value is defined as the last assessment performed prior to administration of the first dose of study treatment.

A mixed effect model for repeated measurements (MMRM) was fitted to the changes from baseline in EQ-5D VAS score for all post-baseline time points up to Week 24. Values estimated from the model are presented in this table.
Time Frame Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20 and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set (FAS) with a valid assessment for the outcome measure. FAS included all participants who were randomized in the study.
Arm/Group Title Remibrutinib 100 mg qd Remibrutinib 100 mg Bid Any Remibrutinib Placebo
Hide Arm/Group Description:
Remibrutinib 100 mg once daily (qd)
Remibrutinib 100 mg twice daily (bid)
Patients in any of the two remibrutinib treatment groups
Placebo group
Overall Number of Participants Analyzed 24 23 47 23
Least Squares Mean (Standard Error)
Unit of Measure: score on scale
Week 2 -3.05  (3.11) -2.86  (3.16) -2.95  (2.22) -3.02  (3.28)
Week 4 -1.74  (2.71) -0.03  (2.86) -0.88  (1.97) 2.99  (2.87)
Week 8 1.46  (3.20) 1.76  (3.20) 1.61  (2.26) 3.44  (3.04)
Week 12 -2.36  (2.71) 1.58  (2.82) -0.39  (1.95) 4.00  (2.64)
Week 16 -0.44  (3.27) 4.27  (3.54) 1.92  (2.41) 1.79  (3.28)
Week 20 -0.91  (3.15) 5.37  (3.33) 2.23  (2.29) 5.29  (3.01)
Week 24 1.81  (3.47) 5.73  (3.65) 3.77  (2.52) 2.07  (3.22)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.494
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-7.84 to 7.96
Estimation Comments Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.866
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.87
Confidence Interval (2-Sided) 95%
-10.81 to 3.06
Estimation Comments Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.684
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.82
Confidence Interval (2-Sided) 95%
-9.37 to 5.73
Estimation Comments Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.908
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.39
Confidence Interval (2-Sided) 95%
-10.93 to 2.14
Estimation Comments Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.487
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.13
Confidence Interval (2-Sided) 95%
-8.00 to 8.26
Estimation Comments Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 20
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.790
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.06
Confidence Interval (2-Sided) 95%
-10.61 to 4.49
Estimation Comments [Not Specified]
Other Statistical Analysis Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.340
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.70
Confidence Interval (2-Sided) 95%
-6.48 to 9.88
Estimation Comments Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 2
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.19
Confidence Interval (2-Sided) 95%
-9.06 to 8.68
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 4
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.71
Confidence Interval (2-Sided) 95%
-9.59 to 6.17
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 8
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.30
Confidence Interval (2-Sided) 95%
-9.34 to 8.74
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 12
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.94
Confidence Interval (2-Sided) 95%
-11.74 to 3.86
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 16
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.71
Confidence Interval (2-Sided) 95%
-14.34 to 4.93
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 20
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -6.29
Confidence Interval (2-Sided) 95%
-15.44 to 2.87
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.92
Confidence Interval (2-Sided) 95%
-14.01 to 6.16
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
6.Secondary Outcome
Title Change From Baseline in Physician Global Assessment Scale (PhGA) Score Over Time
Hide Description

The physician's global assessment scale was used for the Investigator to rate the disease activity of their patient using 100 mm visual analog scale (VAS) ranging from "no disease activity" (0) to "maximal disease activity" (100). A negative change from baseline indicates improvement.

The baseline value is defined as the last assessment performed prior to administration of the first dose of study treatment.

A mixed effect model for repeated measurements (MMRM) was fitted to the changes from baseline in PhGA score for all post-baseline time points up to Week 24. Values estimated from the model are presented in this table.
Time Frame Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20 and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set (FAS) with a valid assessment for the outcome measure. FAS included all participants who were randomized in the study.
Arm/Group Title Remibrutinib 100 mg qd Remibrutinib 100 mg Bid Any Remibrutinib Placebo
Hide Arm/Group Description:
Remibrutinib 100 mg once daily (qd)
Remibrutinib 100 mg twice daily (bid)
Patients in any of the two remibrutinib treatment groups
Placebo group
Overall Number of Participants Analyzed 24 24 48 24
Least Squares Mean (Standard Error)
Unit of Measure: score on scale
Week 2 -4.21  (2.90) -4.02  (2.85) -4.12  (2.04) -4.82  (3.10)
Week 4 -9.58  (2.89) -8.93  (2.96) -9.26  (2.08) -7.28  (2.95)
Week 8 -13.68  (3.39) -13.78  (3.28) -13.73  (2.37) -13.23  (3.16)
Week 12 -13.85  (3.63) -9.45  (3.68) -11.65  (2.60) -17.67  (3.52)
Week 16 -19.37  (3.61) -7.25  (3.74) -13.31  (2.61) -15.90  (3.51)
Week 20 -23.56  (3.43) -17.31  (3.48) -20.43  (2.45) -17.57  (3.20)
Week 24 -21.25  (3.88) -13.15  (3.95) -17.20  (2.78) -20.15  (3.54)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.575
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
-6.75 to 8.16
Estimation Comments Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.294
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.98
Confidence Interval (2-Sided) 95%
-9.22 to 5.27
Estimation Comments Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.450
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.50
Confidence Interval (2-Sided) 95%
-8.40 to 7.41
Estimation Comments Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.913
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 6.02
Confidence Interval (2-Sided) 95%
-2.74 to 14.78
Estimation Comments Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.722
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.59
Confidence Interval (2-Sided) 95%
-6.16 to 11.34
Estimation Comments Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 20
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.241
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.86
Confidence Interval (2-Sided) 95%
-10.96 to 5.24
Estimation Comments [Not Specified]
Other Statistical Analysis Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Any Remibrutinib, Placebo
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.742
Comments one-sided p-value
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.95
Confidence Interval (2-Sided) 95%
-6.09 to 11.99
Estimation Comments Difference (Any remibrutinib - Placebo)
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 2
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.18
Confidence Interval (2-Sided) 95%
-8.28 to 7.91
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 4
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.65
Confidence Interval (2-Sided) 95%
-8.87 to 7.58
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 8
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.10
Confidence Interval (2-Sided) 95%
-9.28 to 9.48
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 12
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.40
Confidence Interval (2-Sided) 95%
-14.71 to 5.90
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 16
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -12.1
Confidence Interval (2-Sided) 95%
-22.47 to -1.77
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 20
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -6.25
Confidence Interval (2-Sided) 95%
-16.00 to 3.50
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Remibrutinib 100 mg qd, Remibrutinib 100 mg Bid
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -8.10
Confidence Interval (2-Sided) 95%
-19.16 to 2.96
Estimation Comments Difference (remibrutinib 100 mg qd - remibrutinib 100 mg bid)
7.Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
Hide Description

Number of participants with TEAEs and serious TEAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as TEAEs. TEAEs are defined as adverse events that started after the first dose of study medications or adverse events present prior to start of double-blind treatment but increased in severity.

The number of participants in each category is reported in the table.
Time Frame From first dose of study treatment up 30 days after last dose (Week 29)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set defined as participants who received at least one dose of the study drug.
Arm/Group Title Remibrutinib 100 mg Bid Remibrutinib 100 mg qd Placebo
Hide Arm/Group Description:
Remibrutinib 100 mg twice daily (bid)
Remibrutinib 100 mg once daily (qd)
Placebo group
Overall Number of Participants Analyzed 24 25 24
Measure Type: Count of Participants
Unit of Measure: Participants
TEAE
22
  91.7%
21
  84.0%
20
  83.3%
Study drug-related TEAE
10
  41.7%
8
  32.0%
9
  37.5%
Serious TEAE
1
   4.2%
1
   4.0%
1
   4.2%
8.Secondary Outcome
Title Maximum Observed Blood Concentration (Cmax) of Remibrutinib at Week 4
Hide Description Remibrutinib was determined in whole blood by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with a lower limit of quantification (LLOQ) of 1.0 ng/mL. Pharmacokinetic (PK) parameters were calculated based on remibrutinib blood concentrations by using the actual recorded sampling times and non-compartmental methods with Phoenix WinNonlin (version 8 or higher). Concentrations below the LLOQ were treated as zero. Cmax is defined as the maximum (peak) observed blood concentration following a dose.
Time Frame pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the PK Analysis Set (PKS) with a valid value for the outcome measure. PKS is defined as participants with at least one available valid PK concentration measurement, who received any study drug, and with no protocol deviations that impact PK data.
Arm/Group Title Remibrutinib 100 mg Bid Remibrutinib 100 mg qd
Hide Arm/Group Description:
Remibrutinib 100 mg twice daily (bid)
Remibrutinib 100 mg once daily (qd)
Overall Number of Participants Analyzed 16 13
Mean (Standard Deviation)
Unit of Measure: ng/mL
183  (82.5) 225  (154)
9.Secondary Outcome
Title Maximum Observed Blood Concentration (Cmax) of Remibrutinib at Week 24
Hide Description Remibrutinib was determined in whole blood by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with a lower limit of quantification (LLOQ) of 1.0 ng/mL. Pharmacokinetic (PK) parameters were calculated based on remibrutinib blood concentrations by using the actual recorded sampling times and non-compartmental methods with Phoenix WinNonlin (version 8 or higher). Concentrations below the LLOQ were treated as zero. Cmax is defined as the maximum (peak) observed blood concentration following a dose.
Time Frame pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the PK Analysis Set (PKS) with a valid value for the outcome measure. PKS is defined as participants with at least one available valid PK concentration measurement, who received any study drug, and with no protocol deviations that impact PK data.
Arm/Group Title Remibrutinib 100 mg Bid Remibrutinib 100 mg qd
Hide Arm/Group Description:
Remibrutinib 100 mg twice daily (bid)
Remibrutinib 100 mg once daily (qd)
Overall Number of Participants Analyzed 14 10
Mean (Standard Deviation)
Unit of Measure: ng/mL
224  (202) 169  (77.9)
10.Secondary Outcome
Title Time to Reach Maximum Observed Blood Concentration (Tmax) of Remibrutinib at Week 4
Hide Description Remibrutinib was determined in whole blood by a validated LC-MS/MS method with a LLOQ of 1.0 ng/mL. Pharmacokinetic (PK) parameters were calculated based on remibrutinib blood concentrations by using the actual recorded sampling times and non-compartmental methods with Phoenix WinNonlin (version 8 or higher). Concentrations below the LLOQ were treated as zero. Tmax is defined as the time to reach maximum (peak) blood concentration following a dose.
Time Frame pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the PK Analysis Set (PKS) with a valid value for the outcome measure. PKS is defined as participants with at least one available valid PK concentration measurement, who received any study drug, and with no protocol deviations that impact PK data.
Arm/Group Title Remibrutinib 100 mg Bid Remibrutinib 100 mg qd
Hide Arm/Group Description:
Remibrutinib 100 mg twice daily (bid)
Remibrutinib 100 mg once daily (qd)
Overall Number of Participants Analyzed 16 13
Median (Full Range)
Unit of Measure: hours
1.00
(0.500 to 3.00)
1.00
(0.500 to 4.00)
11.Secondary Outcome
Title Time to Reach Maximum Observed Blood Concentration (Tmax) of Remibrutinib at Week 24
Hide Description Remibrutinib was determined in whole blood by a validated LC-MS/MS method with a LLOQ of 1.0 ng/mL. Pharmacokinetic (PK) parameters were calculated based on remibrutinib blood concentrations by using the actual recorded sampling times and non-compartmental methods with Phoenix WinNonlin (version 8 or higher). Concentrations below the LLOQ were treated as zero. Tmax is defined as the time to reach maximum (peak) blood concentration following a dose.
Time Frame pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the PK Analysis Set (PKS) with a valid value for the outcome measure. PKS is defined as participants with at least one available valid PK concentration measurement, who received any study drug, and with no protocol deviations that impact PK data.
Arm/Group Title Remibrutinib 100 mg Bid Remibrutinib 100 mg qd
Hide Arm/Group Description:
Remibrutinib 100 mg twice daily (bid)
Remibrutinib 100 mg once daily (qd)
Overall Number of Participants Analyzed 14 10
Median (Full Range)
Unit of Measure: hours
1.00
(0.500 to 3.00)
1.00
(0.500 to 3.08)
12.Secondary Outcome
Title Area Under the Blood Concentration-time Curve Within a Dosing Interval (Tau) at Steady-state (AUCtau) of Remibrutinib at Week 4
Hide Description Remibrutinib was determined in whole blood by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with a lower limit of quantification (LLOQ) of 1.0 ng/mL. Pharmacokinetic (PK) parameters were calculated based on remibrutinib blood concentrations by using the actual recorded sampling times and non-compartmental methods with Phoenix WinNonlin (version 8 or higher). Concentrations below the LLOQ were treated as zero. AUCtau is defined as the area under the blood concentration-time curve calculated/extrapolated to the end of a dosing interval (tau) at steady-state. Tau was 24 hours for the qd dosing group and 12 hours for the bid dosing group. For the calculation of AUCtau, the pre-dose concentrations at Week 4 and Week 24 were duplicated as 24 hours and 12 hours concentrations for the qd and bid groups, respectively. The linear trapezoidal method was used for AUCtau calculation.
Time Frame pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the PK Analysis Set (PKS) with a valid value for the outcome measure. PKS is defined as participants with at least one available valid PK concentration measurement, who received any study drug, and with no protocol deviations that impact PK data.
Arm/Group Title Remibrutinib 100 mg Bid Remibrutinib 100 mg qd
Hide Arm/Group Description:
Remibrutinib 100 mg twice daily (bid)
Remibrutinib 100 mg once daily (qd)
Overall Number of Participants Analyzed 16 8
Mean (Standard Deviation)
Unit of Measure: h*ng/mL
569  (311) 1020  (700)
13.Secondary Outcome
Title Area Under the Blood Concentration-time Curve Within a Dosing Interval (Tau) at Steady-state (AUCtau) of Remibrutinib at Week 24
Hide Description Remibrutinib was determined in whole blood by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with a lower limit of quantification (LLOQ) of 1.0 ng/mL. Pharmacokinetic (PK) parameters were calculated based on remibrutinib blood concentrations by using the actual recorded sampling times and non-compartmental methods with Phoenix WinNonlin (version 8 or higher). Concentrations below the LLOQ were treated as zero. AUCtau is defined as the area under the blood concentration-time curve calculated/extrapolated to the end of a dosing interval (tau) at steady-state. Tau was 24 hours for the qd dosing group and 12 hours for the bid dosing group. For the calculation of AUCtau, the pre-dose concentrations at Week 4 and Week 24 were duplicated as 24 hours and 12 hours concentrations for the qd and bid groups, respectively. The linear trapezoidal method was used for AUCtau calculation.
Time Frame pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the PK Analysis Set (PKS) with a valid value for the outcome measure. PKS is defined as participants with at least one available valid PK concentration measurement, who received any study drug, and with no protocol deviations that impact PK data.
Arm/Group Title Remibrutinib 100 mg Bid Remibrutinib 100 mg qd
Hide Arm/Group Description:
Remibrutinib 100 mg twice daily (bid)
Remibrutinib 100 mg once daily (qd)
Overall Number of Participants Analyzed 14 6
Mean (Standard Deviation)
Unit of Measure: h*ng/mL
670  (380) 636  (306)
14.Secondary Outcome
Title Area Under the Blood Concentration-time Curve From Time Zero to 4 Hours Post-dose (AUC0-4h) of Remibrutinib at Week 4
Hide Description Remibrutinib was determined in whole blood by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with a lower limit of quantification (LLOQ) of 1.0 ng/mL. Pharmacokinetic (PK) parameters were calculated based on remibrutinib blood concentrations by using the actual recorded sampling times and non-compartmental methods with Phoenix WinNonlin (version 8 or higher). Concentrations below the LLOQ were treated as zero. AUC0-4h is defined as the area under the blood concentration-time curve from time zero to 4 hours post-dose, which was the last sampling time. The linear trapezoidal method was used for AUC0-4h calculation.
Time Frame pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the PK Analysis Set (PKS) with a valid value for the outcome measure. PKS is defined as participants with at least one available valid PK concentration measurement, who received any study drug, and with no protocol deviations that impact PK data.
Arm/Group Title Remibrutinib 100 mg Bid Remibrutinib 100 mg qd
Hide Arm/Group Description:
Remibrutinib 100 mg twice daily (bid)
Remibrutinib 100 mg once daily (qd)
Overall Number of Participants Analyzed 16 13
Mean (Standard Deviation)
Unit of Measure: h*ng/mL
351  (169) 393  (207)
15.Secondary Outcome
Title Area Under the Blood Concentration-time Curve From Time Zero to 4 Hours Post-dose (AUC0-4h) of Remibrutinib at Week 24
Hide Description Remibrutinib was determined in whole blood by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with a lower limit of quantification (LLOQ) of 1.0 ng/mL. Pharmacokinetic (PK) parameters were calculated based on remibrutinib blood concentrations by using the actual recorded sampling times and non-compartmental methods with Phoenix WinNonlin (version 8 or higher). Concentrations below the LLOQ were treated as zero. AUC0-4h is defined as the area under the blood concentration-time curve from time zero to 4 hours post-dose, which was the last sampling time. The linear trapezoidal method was used for AUC0-4h calculation.
Time Frame pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the PK Analysis Set (PKS) with a valid value for the outcome measure. PKS is defined as participants with at least one available valid PK concentration measurement, who received any study drug, and with no protocol deviations that impact PK data.
Arm/Group Title Remibrutinib 100 mg Bid Remibrutinib 100 mg qd
Hide Arm/Group Description:
Remibrutinib 100 mg twice daily (bid)
Remibrutinib 100 mg once daily (qd)
Overall Number of Participants Analyzed 14 10
Mean (Standard Deviation)
Unit of Measure: h*ng/mL
420  (259) 317  (144)
16.Secondary Outcome
Title Elimination Half-life (T1/2) of Remibrutinib at Week 4
Hide Description Remibrutinib was determined in whole blood by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with a lower limit of quantification (LLOQ) of 1.0 ng/mL. Pharmacokinetic (PK) parameters were calculated based on remibrutinib blood concentrations by using the actual recorded sampling times and non-compartmental methods with Phoenix WinNonlin (version 8 or higher). Concentrations below the LLOQ were treated as zero. T1/2 is defined as the time taken for the blood concentration, as well as the amount of the drug in the body, to fall by one-half.
Time Frame pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the PK Analysis Set (PKS) with a valid value for the outcome measure. PKS is defined as participants with at least one available valid PK concentration measurement, who received any study drug, and with no protocol deviations that impact PK data.
Arm/Group Title Remibrutinib 100 mg Bid Remibrutinib 100 mg qd
Hide Arm/Group Description:
Remibrutinib 100 mg twice daily (bid)
Remibrutinib 100 mg once daily (qd)
Overall Number of Participants Analyzed 11 9
Mean (Standard Deviation)
Unit of Measure: hours
3.08  (0.998) 3.86  (2.28)
17.Secondary Outcome
Title Elimination Half-life (T1/2) of Remibrutinib at Week 24
Hide Description Remibrutinib was determined in whole blood by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with a lower limit of quantification (LLOQ) of 1.0 ng/mL. Pharmacokinetic (PK) parameters were calculated based on remibrutinib blood concentrations by using the actual recorded sampling times and non-compartmental methods with Phoenix WinNonlin (version 8 or higher). Concentrations below the LLOQ were treated as zero. T1/2 is defined as the time taken for the blood concentration, as well as the amount of the drug in the body, to fall by one-half.
Time Frame pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the PK Analysis Set (PKS) with a valid value for the outcome measure. PKS is defined as participants with at least one available valid PK concentration measurement, who received any study drug, and with no protocol deviations that impact PK data.
Arm/Group Title Remibrutinib 100 mg Bid Remibrutinib 100 mg qd
Hide Arm/Group Description:
Remibrutinib 100 mg twice daily (bid)
Remibrutinib 100 mg once daily (qd)
Overall Number of Participants Analyzed 11 8
Mean (Standard Deviation)
Unit of Measure: hours
3.15  (0.907) 3.88  (1.95)
Time Frame From first dose of study treatment up 30 days after last dose (Week 29)
Adverse Event Reporting Description Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
 
Arm/Group Title Remibrutinib 100 mg Bid Remibrutinib 100 mg qd Any Remibrutinib Placebo Total
Hide Arm/Group Description Remibrutinib 100 mg twice daily (bid) Remibrutinib 100 mg qd Patients in any of the two remibrutinib treatment groups Placebo group All participants
All-Cause Mortality
Remibrutinib 100 mg Bid Remibrutinib 100 mg qd Any Remibrutinib Placebo Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/24 (0.00%)   0/25 (0.00%)   0/49 (0.00%)   0/24 (0.00%)   0/73 (0.00%) 
Hide Serious Adverse Events
Remibrutinib 100 mg Bid Remibrutinib 100 mg qd Any Remibrutinib Placebo Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/24 (4.17%)   1/25 (4.00%)   2/49 (4.08%)   1/24 (4.17%)   3/73 (4.11%) 
Infections and infestations           
COVID-19 pneumonia † 1  1/24 (4.17%)  0/25 (0.00%)  1/49 (2.04%)  0/24 (0.00%)  1/73 (1.37%) 
Herpes zoster † 1  0/24 (0.00%)  1/25 (4.00%)  1/49 (2.04%)  0/24 (0.00%)  1/73 (1.37%) 
Pneumonia † 1  0/24 (0.00%)  0/25 (0.00%)  0/49 (0.00%)  1/24 (4.17%)  1/73 (1.37%) 
1
Term from vocabulary, MedDRA (24.1)
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Remibrutinib 100 mg Bid Remibrutinib 100 mg qd Any Remibrutinib Placebo Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   15/24 (62.50%)   12/25 (48.00%)   27/49 (55.10%)   17/24 (70.83%)   44/73 (60.27%) 
Blood and lymphatic system disorders           
Leukopenia † 1  0/24 (0.00%)  0/25 (0.00%)  0/49 (0.00%)  3/24 (12.50%)  3/73 (4.11%) 
Lymphopenia † 1  0/24 (0.00%)  0/25 (0.00%)  0/49 (0.00%)  3/24 (12.50%)  3/73 (4.11%) 
Neutropenia † 1  1/24 (4.17%)  1/25 (4.00%)  2/49 (4.08%)  2/24 (8.33%)  4/73 (5.48%) 
Gastrointestinal disorders           
Abdominal distension † 1  0/24 (0.00%)  0/25 (0.00%)  0/49 (0.00%)  2/24 (8.33%)  2/73 (2.74%) 
Abdominal pain † 1  1/24 (4.17%)  2/25 (8.00%)  3/49 (6.12%)  1/24 (4.17%)  4/73 (5.48%) 
Diarrhoea † 1  2/24 (8.33%)  0/25 (0.00%)  2/49 (4.08%)  1/24 (4.17%)  3/73 (4.11%) 
Nausea † 1  4/24 (16.67%)  1/25 (4.00%)  5/49 (10.20%)  2/24 (8.33%)  7/73 (9.59%) 
General disorders           
Asthenia † 1  0/24 (0.00%)  2/25 (8.00%)  2/49 (4.08%)  1/24 (4.17%)  3/73 (4.11%) 
Fatigue † 1  3/24 (12.50%)  0/25 (0.00%)  3/49 (6.12%)  2/24 (8.33%)  5/73 (6.85%) 
Infections and infestations           
Nasopharyngitis † 1  2/24 (8.33%)  1/25 (4.00%)  3/49 (6.12%)  3/24 (12.50%)  6/73 (8.22%) 
Sinusitis † 1  0/24 (0.00%)  0/25 (0.00%)  0/49 (0.00%)  2/24 (8.33%)  2/73 (2.74%) 
Upper respiratory tract infection † 1  3/24 (12.50%)  0/25 (0.00%)  3/49 (6.12%)  2/24 (8.33%)  5/73 (6.85%) 
Urinary tract infection † 1  1/24 (4.17%)  1/25 (4.00%)  2/49 (4.08%)  2/24 (8.33%)  4/73 (5.48%) 
Injury, poisoning and procedural complications           
Fall † 1  2/24 (8.33%)  0/25 (0.00%)  2/49 (4.08%)  0/24 (0.00%)  2/73 (2.74%) 
Investigations           
Blood immunoglobulin G increased † 1  0/24 (0.00%)  0/25 (0.00%)  0/49 (0.00%)  2/24 (8.33%)  2/73 (2.74%) 
White blood cell count decreased † 1  2/24 (8.33%)  1/25 (4.00%)  3/49 (6.12%)  0/24 (0.00%)  3/73 (4.11%) 
Metabolism and nutrition disorders           
Hypokalaemia † 1  0/24 (0.00%)  0/25 (0.00%)  0/49 (0.00%)  2/24 (8.33%)  2/73 (2.74%) 
Musculoskeletal and connective tissue disorders           
Arthralgia † 1  1/24 (4.17%)  2/25 (8.00%)  3/49 (6.12%)  1/24 (4.17%)  4/73 (5.48%) 
Back pain † 1  0/24 (0.00%)  2/25 (8.00%)  2/49 (4.08%)  2/24 (8.33%)  4/73 (5.48%) 
Muscle spasms † 1  0/24 (0.00%)  2/25 (8.00%)  2/49 (4.08%)  0/24 (0.00%)  2/73 (2.74%) 
Myalgia † 1  0/24 (0.00%)  1/25 (4.00%)  1/49 (2.04%)  2/24 (8.33%)  3/73 (4.11%) 
Sjogren's syndrome † 1  2/24 (8.33%)  0/25 (0.00%)  2/49 (4.08%)  0/24 (0.00%)  2/73 (2.74%) 
Nervous system disorders           
Headache † 1  1/24 (4.17%)  3/25 (12.00%)  4/49 (8.16%)  5/24 (20.83%)  9/73 (12.33%) 
Skin and subcutaneous tissue disorders           
Petechiae † 1  2/24 (8.33%)  0/25 (0.00%)  2/49 (4.08%)  0/24 (0.00%)  2/73 (2.74%) 
1
Term from vocabulary, MedDRA (24.1)
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. Novartis does not prohibit any investigator from publishing. Any publications from a single site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: Novartis.email@novartis.com
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT04035668    
Other Study ID Numbers: CLOU064E12201
2018-004387-54 ( EudraCT Number )
First Submitted: July 8, 2019
First Posted: July 29, 2019
Results First Submitted: November 21, 2022
Results First Posted: December 20, 2022
Last Update Posted: January 30, 2023