Trial Outcomes & Findings for A Phase 2 Study to Evaluate the Safety and Efficacy of LOU064 in Patients With Moderate to Severe Sjögren's Syndrome (NCT NCT04035668)
NCT ID: NCT04035668
Last Updated: 2023-01-30
Results Overview
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.
TERMINATED
PHASE2
73 participants
Baseline, Week 24
2023-01-30
Participant Flow
Participants took part in 26 investigative sites in 12 countries.
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.
Participant milestones
| Measure |
Remibrutinib 100 mg Bid
Remibrutinib 100 mg twice daily (bid)
|
Remibrutinib 100 mg qd
Remibrutinib 100 mg once daily (qd)
|
Placebo
Placebo group
|
|---|---|---|---|
|
Overall Study
STARTED
|
24
|
25
|
24
|
|
Overall Study
COMPLETED
|
17
|
17
|
21
|
|
Overall Study
NOT COMPLETED
|
7
|
8
|
3
|
Reasons for withdrawal
| Measure |
Remibrutinib 100 mg Bid
Remibrutinib 100 mg twice daily (bid)
|
Remibrutinib 100 mg qd
Remibrutinib 100 mg once daily (qd)
|
Placebo
Placebo group
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
3
|
4
|
2
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
0
|
|
Overall Study
Physician Decision
|
2
|
1
|
1
|
|
Overall Study
Subject Decision
|
2
|
2
|
0
|
Baseline Characteristics
A Phase 2 Study to Evaluate the Safety and Efficacy of LOU064 in Patients With Moderate to Severe Sjögren's Syndrome
Baseline characteristics by cohort
| Measure |
Remibrutinib 100 mg Bid
n=24 Participants
Remibrutinib 100 mg twice daily (bid)
|
Remibrutinib 100 mg qd
n=25 Participants
Remibrutinib 100 mg once daily (qd)
|
Placebo
n=24 Participants
Placebo group
|
Total
n=73 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
49.5 years
STANDARD_DEVIATION 15.21 • n=5 Participants
|
54.8 years
STANDARD_DEVIATION 10.51 • n=7 Participants
|
51.0 years
STANDARD_DEVIATION 13.94 • n=5 Participants
|
51.8 years
STANDARD_DEVIATION 13.34 • n=4 Participants
|
|
Sex: Female, Male
Female
|
24 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
71 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian
|
7 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
21 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White
|
17 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
50 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Unknown
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 24Population: 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.
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.
Outcome measures
| Measure |
Remibrutinib 100 mg qd
n=24 Participants
Remibrutinib 100 mg once daily (qd)
|
Remibrutinib 100 mg Bid
n=24 Participants
Remibrutinib 100 mg twice daily (bid)
|
Any Remibrutinib
n=48 Participants
Patients in any of the two remibrutinib treatment groups
|
Placebo
n=24 Participants
Placebo group
|
|---|---|---|---|---|
|
Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) Total Score at Week 24
|
-4.70 score on scale
Standard Error 0.78
|
-3.70 score on scale
Standard Error 0.80
|
-4.20 score on scale
Standard Error 0.56
|
-1.34 score on scale
Standard Error 0.74
|
SECONDARY outcome
Timeframe: Baseline, Week 2, Week 4, Week 8, Week 12, Week 16 and Week 20Population: 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.
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.
Outcome measures
| Measure |
Remibrutinib 100 mg qd
n=24 Participants
Remibrutinib 100 mg once daily (qd)
|
Remibrutinib 100 mg Bid
n=24 Participants
Remibrutinib 100 mg twice daily (bid)
|
Any Remibrutinib
n=48 Participants
Patients in any of the two remibrutinib treatment groups
|
Placebo
n=24 Participants
Placebo group
|
|---|---|---|---|---|
|
Change From Baseline in ESSDAI Total Score Over Time
Week 4
|
-2.57 score on scale
Standard Error 0.60
|
-2.54 score on scale
Standard Error 0.62
|
-2.55 score on scale
Standard Error 0.43
|
-0.79 score on scale
Standard Error 0.61
|
|
Change From Baseline in ESSDAI Total Score Over Time
Week 2
|
-1.68 score on scale
Standard Error 0.52
|
-1.05 score on scale
Standard Error 0.52
|
-1.37 score on scale
Standard Error 0.37
|
-0.37 score on scale
Standard Error 0.55
|
|
Change From Baseline in ESSDAI Total Score Over Time
Week 8
|
-2.74 score on scale
Standard Error 0.72
|
-2.93 score on scale
Standard Error 0.71
|
-2.83 score on scale
Standard Error 0.51
|
-2.36 score on scale
Standard Error 0.69
|
|
Change From Baseline in ESSDAI Total Score Over Time
Week 12
|
-3.66 score on scale
Standard Error 0.74
|
-2.56 score on scale
Standard Error 0.75
|
-3.11 score on scale
Standard Error 0.53
|
-1.92 score on scale
Standard Error 0.73
|
|
Change From Baseline in ESSDAI Total Score Over Time
Week 16
|
-4.02 score on scale
Standard Error 0.71
|
-2.57 score on scale
Standard Error 0.74
|
-3.29 score on scale
Standard Error 0.51
|
-2.16 score on scale
Standard Error 0.69
|
|
Change From Baseline in ESSDAI Total Score Over Time
Week 20
|
-4.40 score on scale
Standard Error 0.73
|
-3.26 score on scale
Standard Error 0.75
|
-3.83 score on scale
Standard Error 0.52
|
-1.84 score on scale
Standard Error 0.69
|
SECONDARY outcome
Timeframe: Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20 and Week 24Population: 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.
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.
Outcome measures
| Measure |
Remibrutinib 100 mg qd
n=24 Participants
Remibrutinib 100 mg once daily (qd)
|
Remibrutinib 100 mg Bid
n=24 Participants
Remibrutinib 100 mg twice daily (bid)
|
Any Remibrutinib
n=48 Participants
Patients in any of the two remibrutinib treatment groups
|
Placebo
n=24 Participants
Placebo group
|
|---|---|---|---|---|
|
Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) Total Score Over Time
Week 4
|
-0.72 score on scale
Standard Error 0.30
|
-0.14 score on scale
Standard Error 0.30
|
-0.43 score on scale
Standard Error 0.21
|
-0.35 score on scale
Standard Error 0.30
|
|
Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) Total Score Over Time
Week 8
|
-0.83 score on scale
Standard Error 0.31
|
-0.38 score on scale
Standard Error 0.31
|
-0.60 score on scale
Standard Error 0.22
|
-0.57 score on scale
Standard Error 0.29
|
|
Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) Total Score Over Time
Week 2
|
-0.44 score on scale
Standard Error 0.26
|
0.18 score on scale
Standard Error 0.26
|
-0.13 score on scale
Standard Error 0.18
|
-0.09 score on scale
Standard Error 0.27
|
|
Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) Total Score Over Time
Week 12
|
-0.88 score on scale
Standard Error 0.31
|
-0.32 score on scale
Standard Error 0.31
|
-0.60 score on scale
Standard Error 0.22
|
-0.66 score on scale
Standard Error 0.29
|
|
Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) Total Score Over Time
Week 16
|
-0.77 score on scale
Standard Error 0.36
|
-0.39 score on scale
Standard Error 0.37
|
-0.58 score on scale
Standard Error 0.26
|
-0.71 score on scale
Standard Error 0.34
|
|
Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) Total Score Over Time
Week 20
|
-0.92 score on scale
Standard Error 0.38
|
-0.74 score on scale
Standard Error 0.39
|
-0.83 score on scale
Standard Error 0.27
|
-0.92 score on scale
Standard Error 0.36
|
|
Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) Total Score Over Time
Week 24
|
-1.17 score on scale
Standard Error 0.34
|
-0.76 score on scale
Standard Error 0.35
|
-0.96 score on scale
Standard Error 0.24
|
-1.13 score on scale
Standard Error 0.31
|
SECONDARY outcome
Timeframe: Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20 and Week 24Population: 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.
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.
Outcome measures
| Measure |
Remibrutinib 100 mg qd
n=24 Participants
Remibrutinib 100 mg once daily (qd)
|
Remibrutinib 100 mg Bid
n=23 Participants
Remibrutinib 100 mg twice daily (bid)
|
Any Remibrutinib
n=47 Participants
Patients in any of the two remibrutinib treatment groups
|
Placebo
n=23 Participants
Placebo group
|
|---|---|---|---|---|
|
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) Total Score Over Time
Week 2
|
1.80 score on scale
Standard Error 1.32
|
-0.51 score on scale
Standard Error 1.35
|
0.64 score on scale
Standard Error 0.95
|
3.37 score on scale
Standard Error 1.43
|
|
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) Total Score Over Time
Week 4
|
4.83 score on scale
Standard Error 1.50
|
3.97 score on scale
Standard Error 1.57
|
4.40 score on scale
Standard Error 1.09
|
3.51 score on scale
Standard Error 1.58
|
|
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) Total Score Over Time
Week 8
|
4.00 score on scale
Standard Error 1.64
|
3.79 score on scale
Standard Error 1.66
|
3.90 score on scale
Standard Error 1.17
|
5.26 score on scale
Standard Error 1.60
|
|
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) Total Score Over Time
Week 12
|
4.88 score on scale
Standard Error 1.80
|
4.25 score on scale
Standard Error 1.86
|
4.56 score on scale
Standard Error 1.30
|
7.30 score on scale
Standard Error 1.77
|
|
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) Total Score Over Time
Week 16
|
4.40 score on scale
Standard Error 1.97
|
3.29 score on scale
Standard Error 2.08
|
3.84 score on scale
Standard Error 1.44
|
7.73 score on scale
Standard Error 1.98
|
|
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) Total Score Over Time
Week 20
|
10.01 score on scale
Standard Error 2.20
|
4.32 score on scale
Standard Error 2.30
|
7.16 score on scale
Standard Error 1.60
|
5.77 score on scale
Standard Error 2.17
|
|
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) Total Score Over Time
Week 24
|
8.17 score on scale
Standard Error 2.45
|
4.64 score on scale
Standard Error 2.55
|
6.40 score on scale
Standard Error 1.77
|
7.45 score on scale
Standard Error 2.32
|
SECONDARY outcome
Timeframe: Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20 and Week 24Population: 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.
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.
Outcome measures
| Measure |
Remibrutinib 100 mg qd
n=24 Participants
Remibrutinib 100 mg once daily (qd)
|
Remibrutinib 100 mg Bid
n=23 Participants
Remibrutinib 100 mg twice daily (bid)
|
Any Remibrutinib
n=47 Participants
Patients in any of the two remibrutinib treatment groups
|
Placebo
n=23 Participants
Placebo group
|
|---|---|---|---|---|
|
Change From Baseline in EuroQual 5 Dimensions (EQ-5D) VAS Score Over Time
Week 8
|
1.46 score on scale
Standard Error 3.20
|
1.76 score on scale
Standard Error 3.20
|
1.61 score on scale
Standard Error 2.26
|
3.44 score on scale
Standard Error 3.04
|
|
Change From Baseline in EuroQual 5 Dimensions (EQ-5D) VAS Score Over Time
Week 20
|
-0.91 score on scale
Standard Error 3.15
|
5.37 score on scale
Standard Error 3.33
|
2.23 score on scale
Standard Error 2.29
|
5.29 score on scale
Standard Error 3.01
|
|
Change From Baseline in EuroQual 5 Dimensions (EQ-5D) VAS Score Over Time
Week 2
|
-3.05 score on scale
Standard Error 3.11
|
-2.86 score on scale
Standard Error 3.16
|
-2.95 score on scale
Standard Error 2.22
|
-3.02 score on scale
Standard Error 3.28
|
|
Change From Baseline in EuroQual 5 Dimensions (EQ-5D) VAS Score Over Time
Week 4
|
-1.74 score on scale
Standard Error 2.71
|
-0.03 score on scale
Standard Error 2.86
|
-0.88 score on scale
Standard Error 1.97
|
2.99 score on scale
Standard Error 2.87
|
|
Change From Baseline in EuroQual 5 Dimensions (EQ-5D) VAS Score Over Time
Week 12
|
-2.36 score on scale
Standard Error 2.71
|
1.58 score on scale
Standard Error 2.82
|
-0.39 score on scale
Standard Error 1.95
|
4.00 score on scale
Standard Error 2.64
|
|
Change From Baseline in EuroQual 5 Dimensions (EQ-5D) VAS Score Over Time
Week 16
|
-0.44 score on scale
Standard Error 3.27
|
4.27 score on scale
Standard Error 3.54
|
1.92 score on scale
Standard Error 2.41
|
1.79 score on scale
Standard Error 3.28
|
|
Change From Baseline in EuroQual 5 Dimensions (EQ-5D) VAS Score Over Time
Week 24
|
1.81 score on scale
Standard Error 3.47
|
5.73 score on scale
Standard Error 3.65
|
3.77 score on scale
Standard Error 2.52
|
2.07 score on scale
Standard Error 3.22
|
SECONDARY outcome
Timeframe: Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20 and Week 24Population: 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.
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.
Outcome measures
| Measure |
Remibrutinib 100 mg qd
n=24 Participants
Remibrutinib 100 mg once daily (qd)
|
Remibrutinib 100 mg Bid
n=24 Participants
Remibrutinib 100 mg twice daily (bid)
|
Any Remibrutinib
n=48 Participants
Patients in any of the two remibrutinib treatment groups
|
Placebo
n=24 Participants
Placebo group
|
|---|---|---|---|---|
|
Change From Baseline in Physician Global Assessment Scale (PhGA) Score Over Time
Week 2
|
-4.21 score on scale
Standard Error 2.90
|
-4.02 score on scale
Standard Error 2.85
|
-4.12 score on scale
Standard Error 2.04
|
-4.82 score on scale
Standard Error 3.10
|
|
Change From Baseline in Physician Global Assessment Scale (PhGA) Score Over Time
Week 4
|
-9.58 score on scale
Standard Error 2.89
|
-8.93 score on scale
Standard Error 2.96
|
-9.26 score on scale
Standard Error 2.08
|
-7.28 score on scale
Standard Error 2.95
|
|
Change From Baseline in Physician Global Assessment Scale (PhGA) Score Over Time
Week 8
|
-13.68 score on scale
Standard Error 3.39
|
-13.78 score on scale
Standard Error 3.28
|
-13.73 score on scale
Standard Error 2.37
|
-13.23 score on scale
Standard Error 3.16
|
|
Change From Baseline in Physician Global Assessment Scale (PhGA) Score Over Time
Week 12
|
-13.85 score on scale
Standard Error 3.63
|
-9.45 score on scale
Standard Error 3.68
|
-11.65 score on scale
Standard Error 2.60
|
-17.67 score on scale
Standard Error 3.52
|
|
Change From Baseline in Physician Global Assessment Scale (PhGA) Score Over Time
Week 16
|
-19.37 score on scale
Standard Error 3.61
|
-7.25 score on scale
Standard Error 3.74
|
-13.31 score on scale
Standard Error 2.61
|
-15.90 score on scale
Standard Error 3.51
|
|
Change From Baseline in Physician Global Assessment Scale (PhGA) Score Over Time
Week 20
|
-23.56 score on scale
Standard Error 3.43
|
-17.31 score on scale
Standard Error 3.48
|
-20.43 score on scale
Standard Error 2.45
|
-17.57 score on scale
Standard Error 3.20
|
|
Change From Baseline in Physician Global Assessment Scale (PhGA) Score Over Time
Week 24
|
-21.25 score on scale
Standard Error 3.88
|
-13.15 score on scale
Standard Error 3.95
|
-17.20 score on scale
Standard Error 2.78
|
-20.15 score on scale
Standard Error 3.54
|
SECONDARY outcome
Timeframe: From first dose of study treatment up 30 days after last dose (Week 29)Population: Safety Analysis Set defined as participants who received at least one dose of the study drug.
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.
Outcome measures
| Measure |
Remibrutinib 100 mg qd
n=24 Participants
Remibrutinib 100 mg once daily (qd)
|
Remibrutinib 100 mg Bid
n=25 Participants
Remibrutinib 100 mg twice daily (bid)
|
Any Remibrutinib
n=24 Participants
Patients in any of the two remibrutinib treatment groups
|
Placebo
Placebo group
|
|---|---|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
TEAE
|
22 Participants
|
21 Participants
|
20 Participants
|
—
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
Study drug-related TEAE
|
10 Participants
|
8 Participants
|
9 Participants
|
—
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
Serious TEAE
|
1 Participants
|
1 Participants
|
1 Participants
|
—
|
SECONDARY outcome
Timeframe: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 4Population: 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.
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.
Outcome measures
| Measure |
Remibrutinib 100 mg qd
n=16 Participants
Remibrutinib 100 mg once daily (qd)
|
Remibrutinib 100 mg Bid
n=13 Participants
Remibrutinib 100 mg twice daily (bid)
|
Any Remibrutinib
Patients in any of the two remibrutinib treatment groups
|
Placebo
Placebo group
|
|---|---|---|---|---|
|
Maximum Observed Blood Concentration (Cmax) of Remibrutinib at Week 4
|
183 ng/mL
Standard Deviation 82.5
|
225 ng/mL
Standard Deviation 154
|
—
|
—
|
SECONDARY outcome
Timeframe: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 24Population: 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.
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.
Outcome measures
| Measure |
Remibrutinib 100 mg qd
n=14 Participants
Remibrutinib 100 mg once daily (qd)
|
Remibrutinib 100 mg Bid
n=10 Participants
Remibrutinib 100 mg twice daily (bid)
|
Any Remibrutinib
Patients in any of the two remibrutinib treatment groups
|
Placebo
Placebo group
|
|---|---|---|---|---|
|
Maximum Observed Blood Concentration (Cmax) of Remibrutinib at Week 24
|
224 ng/mL
Standard Deviation 202
|
169 ng/mL
Standard Deviation 77.9
|
—
|
—
|
SECONDARY outcome
Timeframe: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 4Population: 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.
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.
Outcome measures
| Measure |
Remibrutinib 100 mg qd
n=16 Participants
Remibrutinib 100 mg once daily (qd)
|
Remibrutinib 100 mg Bid
n=13 Participants
Remibrutinib 100 mg twice daily (bid)
|
Any Remibrutinib
Patients in any of the two remibrutinib treatment groups
|
Placebo
Placebo group
|
|---|---|---|---|---|
|
Time to Reach Maximum Observed Blood Concentration (Tmax) of Remibrutinib at Week 4
|
1.00 hours
Interval 0.5 to 3.0
|
1.00 hours
Interval 0.5 to 4.0
|
—
|
—
|
SECONDARY outcome
Timeframe: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 24Population: 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.
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.
Outcome measures
| Measure |
Remibrutinib 100 mg qd
n=14 Participants
Remibrutinib 100 mg once daily (qd)
|
Remibrutinib 100 mg Bid
n=10 Participants
Remibrutinib 100 mg twice daily (bid)
|
Any Remibrutinib
Patients in any of the two remibrutinib treatment groups
|
Placebo
Placebo group
|
|---|---|---|---|---|
|
Time to Reach Maximum Observed Blood Concentration (Tmax) of Remibrutinib at Week 24
|
1.00 hours
Interval 0.5 to 3.0
|
1.00 hours
Interval 0.5 to 3.08
|
—
|
—
|
SECONDARY outcome
Timeframe: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 4Population: 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.
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.
Outcome measures
| Measure |
Remibrutinib 100 mg qd
n=16 Participants
Remibrutinib 100 mg once daily (qd)
|
Remibrutinib 100 mg Bid
n=8 Participants
Remibrutinib 100 mg twice daily (bid)
|
Any Remibrutinib
Patients in any of the two remibrutinib treatment groups
|
Placebo
Placebo group
|
|---|---|---|---|---|
|
Area Under the Blood Concentration-time Curve Within a Dosing Interval (Tau) at Steady-state (AUCtau) of Remibrutinib at Week 4
|
569 h*ng/mL
Standard Deviation 311
|
1020 h*ng/mL
Standard Deviation 700
|
—
|
—
|
SECONDARY outcome
Timeframe: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 24Population: 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.
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.
Outcome measures
| Measure |
Remibrutinib 100 mg qd
n=14 Participants
Remibrutinib 100 mg once daily (qd)
|
Remibrutinib 100 mg Bid
n=6 Participants
Remibrutinib 100 mg twice daily (bid)
|
Any Remibrutinib
Patients in any of the two remibrutinib treatment groups
|
Placebo
Placebo group
|
|---|---|---|---|---|
|
Area Under the Blood Concentration-time Curve Within a Dosing Interval (Tau) at Steady-state (AUCtau) of Remibrutinib at Week 24
|
670 h*ng/mL
Standard Deviation 380
|
636 h*ng/mL
Standard Deviation 306
|
—
|
—
|
SECONDARY outcome
Timeframe: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 4Population: 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.
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.
Outcome measures
| Measure |
Remibrutinib 100 mg qd
n=16 Participants
Remibrutinib 100 mg once daily (qd)
|
Remibrutinib 100 mg Bid
n=13 Participants
Remibrutinib 100 mg twice daily (bid)
|
Any Remibrutinib
Patients in any of the two remibrutinib treatment groups
|
Placebo
Placebo group
|
|---|---|---|---|---|
|
Area Under the Blood Concentration-time Curve From Time Zero to 4 Hours Post-dose (AUC0-4h) of Remibrutinib at Week 4
|
351 h*ng/mL
Standard Deviation 169
|
393 h*ng/mL
Standard Deviation 207
|
—
|
—
|
SECONDARY outcome
Timeframe: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 24Population: 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.
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.
Outcome measures
| Measure |
Remibrutinib 100 mg qd
n=14 Participants
Remibrutinib 100 mg once daily (qd)
|
Remibrutinib 100 mg Bid
n=10 Participants
Remibrutinib 100 mg twice daily (bid)
|
Any Remibrutinib
Patients in any of the two remibrutinib treatment groups
|
Placebo
Placebo group
|
|---|---|---|---|---|
|
Area Under the Blood Concentration-time Curve From Time Zero to 4 Hours Post-dose (AUC0-4h) of Remibrutinib at Week 24
|
420 h*ng/mL
Standard Deviation 259
|
317 h*ng/mL
Standard Deviation 144
|
—
|
—
|
SECONDARY outcome
Timeframe: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 4Population: 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.
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.
Outcome measures
| Measure |
Remibrutinib 100 mg qd
n=11 Participants
Remibrutinib 100 mg once daily (qd)
|
Remibrutinib 100 mg Bid
n=9 Participants
Remibrutinib 100 mg twice daily (bid)
|
Any Remibrutinib
Patients in any of the two remibrutinib treatment groups
|
Placebo
Placebo group
|
|---|---|---|---|---|
|
Elimination Half-life (T1/2) of Remibrutinib at Week 4
|
3.08 hours
Standard Deviation 0.998
|
3.86 hours
Standard Deviation 2.28
|
—
|
—
|
SECONDARY outcome
Timeframe: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 24Population: 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.
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.
Outcome measures
| Measure |
Remibrutinib 100 mg qd
n=11 Participants
Remibrutinib 100 mg once daily (qd)
|
Remibrutinib 100 mg Bid
n=8 Participants
Remibrutinib 100 mg twice daily (bid)
|
Any Remibrutinib
Patients in any of the two remibrutinib treatment groups
|
Placebo
Placebo group
|
|---|---|---|---|---|
|
Elimination Half-life (T1/2) of Remibrutinib at Week 24
|
3.15 hours
Standard Deviation 0.907
|
3.88 hours
Standard Deviation 1.95
|
—
|
—
|
Adverse Events
Remibrutinib 100 mg Bid
Remibrutinib 100 mg qd
Any Remibrutinib
Placebo
Total
Serious adverse events
| Measure |
Remibrutinib 100 mg Bid
n=24 participants at risk
Remibrutinib 100 mg twice daily (bid)
|
Remibrutinib 100 mg qd
n=25 participants at risk
Remibrutinib 100 mg qd
|
Any Remibrutinib
n=49 participants at risk
Patients in any of the two remibrutinib treatment groups
|
Placebo
n=24 participants at risk
Placebo group
|
Total
n=73 participants at risk
All participants
|
|---|---|---|---|---|---|
|
Infections and infestations
COVID-19 pneumonia
|
4.2%
1/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
0.00%
0/25 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
2.0%
1/49 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
0.00%
0/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
1.4%
1/73 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
4.0%
1/25 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
2.0%
1/49 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
0.00%
0/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
1.4%
1/73 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
|
Infections and infestations
Pneumonia
|
0.00%
0/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
0.00%
0/25 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
0.00%
0/49 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
4.2%
1/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
1.4%
1/73 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
Other adverse events
| Measure |
Remibrutinib 100 mg Bid
n=24 participants at risk
Remibrutinib 100 mg twice daily (bid)
|
Remibrutinib 100 mg qd
n=25 participants at risk
Remibrutinib 100 mg qd
|
Any Remibrutinib
n=49 participants at risk
Patients in any of the two remibrutinib treatment groups
|
Placebo
n=24 participants at risk
Placebo group
|
Total
n=73 participants at risk
All participants
|
|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
0.00%
0/25 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
0.00%
0/49 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
12.5%
3/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
4.1%
3/73 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
|
Blood and lymphatic system disorders
Lymphopenia
|
0.00%
0/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
0.00%
0/25 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
0.00%
0/49 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
12.5%
3/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
4.1%
3/73 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
|
Blood and lymphatic system disorders
Neutropenia
|
4.2%
1/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
4.0%
1/25 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
4.1%
2/49 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
8.3%
2/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
5.5%
4/73 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
0.00%
0/25 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
0.00%
0/49 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
8.3%
2/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
2.7%
2/73 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
|
Gastrointestinal disorders
Abdominal pain
|
4.2%
1/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
8.0%
2/25 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
6.1%
3/49 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
4.2%
1/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
5.5%
4/73 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
|
Gastrointestinal disorders
Diarrhoea
|
8.3%
2/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
0.00%
0/25 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
4.1%
2/49 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
4.2%
1/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
4.1%
3/73 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
|
Gastrointestinal disorders
Nausea
|
16.7%
4/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
4.0%
1/25 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
10.2%
5/49 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
8.3%
2/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
9.6%
7/73 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
|
General disorders
Asthenia
|
0.00%
0/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
8.0%
2/25 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
4.1%
2/49 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
4.2%
1/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
4.1%
3/73 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
|
General disorders
Fatigue
|
12.5%
3/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
0.00%
0/25 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
6.1%
3/49 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
8.3%
2/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
6.8%
5/73 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
|
Infections and infestations
Nasopharyngitis
|
8.3%
2/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
4.0%
1/25 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
6.1%
3/49 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
12.5%
3/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
8.2%
6/73 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
|
Infections and infestations
Sinusitis
|
0.00%
0/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
0.00%
0/25 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
0.00%
0/49 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
8.3%
2/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
2.7%
2/73 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
|
Infections and infestations
Upper respiratory tract infection
|
12.5%
3/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
0.00%
0/25 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
6.1%
3/49 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
8.3%
2/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
6.8%
5/73 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
|
Infections and infestations
Urinary tract infection
|
4.2%
1/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
4.0%
1/25 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
4.1%
2/49 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
8.3%
2/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
5.5%
4/73 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
|
Injury, poisoning and procedural complications
Fall
|
8.3%
2/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
0.00%
0/25 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
4.1%
2/49 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
0.00%
0/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
2.7%
2/73 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
|
Investigations
Blood immunoglobulin G increased
|
0.00%
0/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
0.00%
0/25 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
0.00%
0/49 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
8.3%
2/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
2.7%
2/73 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
|
Investigations
White blood cell count decreased
|
8.3%
2/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
4.0%
1/25 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
6.1%
3/49 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
0.00%
0/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
4.1%
3/73 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
0.00%
0/25 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
0.00%
0/49 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
8.3%
2/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
2.7%
2/73 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
4.2%
1/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
8.0%
2/25 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
6.1%
3/49 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
4.2%
1/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
5.5%
4/73 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
8.0%
2/25 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
4.1%
2/49 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
8.3%
2/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
5.5%
4/73 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
8.0%
2/25 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
4.1%
2/49 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
0.00%
0/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
2.7%
2/73 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
4.0%
1/25 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
2.0%
1/49 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
8.3%
2/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
4.1%
3/73 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
|
Musculoskeletal and connective tissue disorders
Sjogren's syndrome
|
8.3%
2/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
0.00%
0/25 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
4.1%
2/49 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
0.00%
0/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
2.7%
2/73 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
|
Nervous system disorders
Headache
|
4.2%
1/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
12.0%
3/25 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
8.2%
4/49 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
20.8%
5/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
12.3%
9/73 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
8.3%
2/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
0.00%
0/25 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
4.1%
2/49 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
0.00%
0/24 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
2.7%
2/73 • From first dose of study treatment up 30 days after last dose (Week 29)
Any sign or symptom that occurs from first dose of study treatment up to 30 days after last dose.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER