Primary Sjogren Syndrome
Conditions
Keywords
Sjogren, VAY736, ianalumab, pSS
Brief summary
The purpose of this study was to determine the dose-response relationship of VAY736 for key efficacy and safety parameters
Detailed description
This was a randomized, double-blind, placebo-controlled, multicenter, parallel-group trial that was divided into 4 study periods. Period 1: A screening period of 4 weeks to assess patient eligibility. Patients could be re-screened only once, and no study-related re-screening procedure could be performed prior to written re-consent by the patient. Period 2: A blinded treatment period of 24 weeks. At baseline, eligible patients were randomized to one of three ianalumab dose arms (VAY736 5 mg, 50 mg or 300 mg s.c.) or a placebo arm (placebo s.c.). Blinded study drug was administered every four weeks (q4w) for a 24-week period. Except for Japan, randomization was stratified by baseline ESSDAI score (\<10 or ≥10 based on weighted scores). Separate blocks of randomization numbers were generated for patients in Japan versus the other countries participating to ensure that Japanese patients were equally distributed across all treatment groups in the study. The primary endpoint was assessed at the end of Period 2 (Week 24). Treatment assignment in Period 2 remained double-blinded until the end of Period 3. Period 3: An extended blinded treatment period of 28 weeks. After Week 24 assessments, patients in the ianalumab 300 mg arm were re-randomized in a 1:1 ratio to either continue on ianalumab 300 mg s.c. q4w or switch to matching placebo up to Week 52. Patients who received placebo during Period 2 were switched to ianalumab 150 mg s.c q4w up to Week 52. Patients who received 5 mg and 50 mg s.c. in Period 2 proceeded directly to safety follow-up (Period 4). Treatment assignment in Period 3 remained double-blinded. Period 4: A post-treatment safety follow-up period. Patients who prematurely discontinued the study treatment at any time point or completed the treatment as planned entered the safety follow-up period. The minimum required duration of follow-up in the study was 20 weeks from the last administration of the study treatment (mandatory follow-up). The maximum duration of the follow-up was 2 years from the last dose of the study treatment, and it was defined by the level of recovery of CD19+ B-cells: conditional follow up (with reduced visit frequency) until CD19+ B-cell levels return to at least 80% of baseline or 50 cells/µL, whichever occurred first. Patients who had not yet recovered their B-cell counts two years after last ianalumab dosing were discharged from the study and had undergone their End of Study (EoS) visit. Patients who were treated with another immunomodulatory or immunosuppressive treatment (e.g., azathioprine, cyclophosphamide, high dose glucocorticosteroids) after completion of the minimum 20-week safety follow-up period were excluded from further safety follow-up.
Interventions
BIOLOGICALVAY736
VAY736
OTHERPlacebo
Placebo control
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
This was a randomized, double-blind, placebo-controlled, multicenter, parallel-group trial which planned to enroll approximately 180 patients with moderate to severe primary Sjögren's syndrome. The study was divided into 4 study periods: Period 1: 4-week Screening to assess patient eligibility. Period 2: 24-week Blinded treatment period. Period 3: An extended blinded treatment period of 28 weeks. After Week 24 assessments, patients in the ianalumab 300 mg arm were re-randomized in a 1:1 ratio to either continue on ianalumab 300 mg s.c. q4w or switch to matching placebo up to Week 52. Period 4: Post-treatment safety follow-up period. Patients who prematurely discontinued the study treatment at any time point or completed the treatment as planned entered the safety follow-up period.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Fulfilled revised American European Consensus Group criteria for pSS * Seropositive at screening for anti-Ro/SSA antibodies * Screening ESSDAI value \>=6 scored from 7 domains: articular, cutaneous, glandular, lymphoadenopathy, constitutional, biologic and hematologic.
Exclusion criteria
* Secondary Sjogren's syndrome * Use of other investigational drugs * Active viral, bacterial or other infections * Positive hepatitis B, hepatitis C, HIV or tuberculosis test results at screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Least Squares Mean Change From Baseline in ESSDAI Score at Week 24 | Baseline, Week 24 | The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) instrument contains 12 organ-specific domains contributing to disease activity. For each domain, features of disease activity are scored in 3 or 4 levels according to their severity. These scores are then summed across the 12 domains in a weighted manner to provide the total score ranging 0-123. Higher scores on the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) scale are associated with poorer health states. A negative change from baseline indicates improvement in disease status. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Least Squares Mean Change From Baseline in ESSPRI Score at Week 24 | Baseline, Week 24 | The EULAR Sjörgen's Syndrome Patient Reported Index (ESSPRI) is an established disease outcome measure for Sjögren's syndrome that is calculated by averaging the scales for pain, fatigue and dryness. The total score is the mean score of the 3 scales and ranges between 0 and 10 with higher values indicating more severity of symptoms. A negative change from baseline is a favorable outcome. |
| Least Squares Mean Change From Baseline in ESSPRI Score at Weeks 4, 8, 12 and 16 | Baseline, Week 4, Week 8, Week 12, Week 16 | The EULAR Sjörgen's Syndrome Patient Reported Index (ESSPRI) is an established disease outcome measure for Sjögren's syndrome that is calculated by averaging the scales for pain, fatigue and dryness. The total score is the mean score of the 3 scales and ranges between 0 and 10 with higher values indicating more severity of symptoms. A negative change from baseline is a favorable outcome. |
| Least Squares Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F) Score Over 24 Weeks | Baseline, Week 24 | The Functional Assessment of Chronic Illness Therapy-Fatigue Scale (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 previous week. The level of fatigue is measured on a four-point Likert scale (4 = not at all fatigued to 0 = very much fatigued). The global score ranges between 0 and 52, with higher scores indicating less fatigue. |
| Least Squares Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F) Score at Weeks 4, 8, 12 and 16 | Baseline, Weeks 4, 8, 12 and 16 | The Functional Assessment of Chronic Illness Therapy-Fatigue Scale (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 previous week. The level of fatigue is measured on a four-point Likert scale (4 = not at all fatigued to 0 = very much fatigued). The global score ranges between 0 and 52, with higher scores indicating less fatigue. |
| Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) Over 24 Weeks | Baseline, Week 24 | The SF36 includes 8 scale scores (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health) and two summary scores, the physical and mental component scores. The first four and last four scales comprise physical and mental component scores, respectively. The range of scores of the physical component (PCS) and mental component (MCS) is 0 (lowest or worst possible level of functioning) to 100 (highest or best possible level of functioning). |
| Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16 | Baseline, Weeks 4, 8, 12 and 16 | The SF36 includes 8 scale scores (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health) and two summary scores, the physical and mental component scores. The first four and last four scales comprise physical and mental component scores, respectively. The range of scores of the physical component (PCS) and mental component (MCS) is 0 (lowest or worst possible level of functioning) to 100 (highest or best possible level of functioning). |
| Least Squares Mean Change From Baseline in ESSDAI Score at Weeks 4, 8, 12, and 16 | Baseline, Week 4, Week 8, Week 12, Week 16 | The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) instrument contains 12 organ-specific domains contributing to disease activity. For each domain, features of disease activity are scored in 3 or 4 levels according to their severity. These scores are then summed across the 12 domains in a weighted manner to provide the total score ranging 0-123. Higher scores on the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) scale are associated with poorer health states. A negative change from baseline indicates improvement in disease status. |
| Least Squares Mean Change From Baseline in Physician's Global Assessment (PhGA) of Patient's Overall Disease Activity Using Patient Visual Analog Scale (VAS) at Weeks 4, 8, 12 and 16 | Baseline, Weeks 4, 8, 12 and 16 | Physician global assessment of overall disease activity (PhGA) was performed using a 100 mm visual analogue scale (VAS) ranging from no disease activity (score 0) to maximal disease activity (score 100), after the question Considering all the ways the disease affects your patient, draw a line on the scale for how well his or her condition is today. A negative change from baseline is a favourable outcome. |
| Patient's Global Assessment (PaGA) Score at Weeks 4, 8, 12, 16 and 24 | Weeks 4, 8, 12, 16 and 24 | The PaGA of disease activity was performed using a 100 mm Visual Analog Scale (VAS) ranging from 0 (no disease activity) to 100 (maximal disease activity), in response to the question Considering all the ways Sjögren's syndrome affects you, please draw a line on the scale to indicate how well you are doing today. A negative change from baseline is a favourable outcome. |
| Least Squares Mean Change From Baseline in Salivary Flow Rate at Week 24 | Baseline, 24 weeks | Change from baseline in salivary flow rate (unstimulated and stimulated) at 24 weeks as compared to placebo. Unstimulated saliva is a mix of serous and mucous secretions coming primarily from the submandibular and minor salivary glands. The parotid gland produces the largest volume of stimulated saliva. Stimulated saliva accounts for 80-90% of daily salivary production. |
| Percent Change From Baseline in Whole Blood CD19+ B-cell Counts. | Baseline, Week 24, Week 28 | B-cell counts were measured before, during and after treatment with VAY736. After stopping VAY736 treatment they were used to monitor patients for time to recovery of adequate CD19+ B cell counts prior to discharge from the study. Change from baseline in B-cell counts before, during and after treatment with VAY736 as well as the time to recover to baseline like values (defined as at least 80% of baseline counts or \>= 50 cells/μL) were analyzed by descriptive statistics. Baseline was defined as the last assessment performed on or prior to the date of administration of the first dose of study treatment. |
| Kaplan-Meier Analysis for Time to Recovery to Baseline Like Values for B-cell Counts | Up to two years from last dose patient received. | B-cell counts were measured before, during and after treatment with VAY736. After stopping VAY736 treatment they were used to monitor patients for time to recovery of adequate CD19+ B cell counts prior to discharge from the study. Change from baseline in B-cell counts before, during and after treatment with VAY736 as well as the time to recover to baseline like values (defined as at least 80% of baseline counts or \>= 50 cells/μL) were analyzed by descriptive statistics. Baseline was defined as the last assessment performed on or prior to the date of administration of the first dose of study treatment. |
| Peak Serum Concentration of VAY736 | baseline to week 24, then week 28 | Pharmacokinetic Concentrations This outcome only applies to patients who received at least one dose of VAY739 (so not applicable to placebo) |
| Least Squares Mean Change From Baseline in Physician's Global Assessment (PhGA) of Patient's Overall Disease Activity Using Patient Visual Analog Scale (VAS) Over 24 Weeks | Baseline, 24 weeks | Physician global assessment of overall disease activity (PhGA) was performed using a 100 mm visual analogue scale (VAS) ranging from no disease activity (score 0) to maximal disease activity (score 100), after the question Considering all the ways the disease affects your patient, draw a line on the scale for how well his or her condition is today. A negative change from baseline is a favourable outcome. |
Countries
Argentina, Austria, Belgium, Chile, France, Germany, Hungary, Israel, Italy, Japan, Netherlands, Poland, Portugal, Romania, Russia, Spain, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
190 Patients were enrolled from 56 centers in 19 countries.
Pre-assignment details
Patients who were in the placebo arm in Period 2 were switched to VAY736 - 150mg s.c. administration every 4 weeks in Period 3. At the end of Period 2, patients from the VAY736 300mg every 4 weeks arm were re-randomized to either i) double-blind VAY736 300mg every 4 weeks or ii) double-blind placebo every four weeks. All other patients proceeded directly from Period 2 to Period 4 (Safety Follow-Up).
Participants by arm
| Arm | Count |
|---|---|
| Placebo (Up to Week 24) Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period) | 49 |
| VAY736 - 5 mg (Up to Week 24) Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period) | 47 |
| VAY736 - 50 mg (Up to Week 24) Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period) | 47 |
| VAY736 - 300 mg (Up to Week 24) Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period) | 47 |
| Total | 190 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Period 2 (Randomized Set: Up to Week 24) | Adverse Event | 0 | 2 | 2 | 0 | 0 | 0 | 0 |
| Period 2 (Randomized Set: Up to Week 24) | New therapy for indication | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 2 (Randomized Set: Up to Week 24) | Non-compliance with treatment | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Period 2 (Randomized Set: Up to Week 24) | Pregnancy | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Period 2 (Randomized Set: Up to Week 24) | Withdrawal by Subject | 1 | 1 | 2 | 0 | 0 | 0 | 0 |
| Period 2 (Randomized Set: Up to Week 24) | Withdrawal of Informed Consent | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Period 3 (Randomized Set / Weeks: 24-52) | Adverse Event | 0 | 0 | 0 | 0 | 5 | 0 | 2 |
| Period 3 (Randomized Set / Weeks: 24-52) | Patient/guardian decision | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Period 3 (Randomized Set / Weeks: 24-52) | Pregnancy | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Period 4 (Safety Follow-Up) | Lack of Efficacy | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Period 4 (Safety Follow-Up) | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Period 4 (Safety Follow-Up) | New therapy for indication | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Period 4 (Safety Follow-Up) | Withdrawal by Subject | 0 | 2 | 3 | 1 | 2 | 2 | 0 |
| Period 4 (Safety Follow-Up) | Withdrawal of informed consent | 0 | 3 | 1 | 2 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo (Up to Week 24) | VAY736 - 5 mg (Up to Week 24) | VAY736 - 50 mg (Up to Week 24) | VAY736 - 300 mg (Up to Week 24) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 47.9 Years STANDARD_DEVIATION 12.44 | 52.5 Years STANDARD_DEVIATION 13.64 | 51.0 Years STANDARD_DEVIATION 11.12 | 49.1 Years STANDARD_DEVIATION 15.41 | 50.9 Years STANDARD_DEVIATION 13.48 |
| Race/Ethnicity, Customized Asian | 4 Participants | 3 Participants | 10 Participants | 5 Participants | 22 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 44 Participants | 42 Participants | 37 Participants | 42 Participants | 165 Participants |
| Sex: Female, Male Female | 47 Participants | 46 Participants | 41 Participants | 46 Participants | 180 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 6 Participants | 1 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 49 | 0 / 47 | 0 / 47 | 0 / 47 | 0 / 141 | 0 / 190 | 0 / 47 | 0 / 47 | 0 / 47 | 0 / 26 | 0 / 21 | 0 / 47 | 0 / 188 |
| other Total, other adverse events | 33 / 49 | 40 / 47 | 34 / 47 | 41 / 47 | 115 / 141 | 148 / 190 | 41 / 47 | 37 / 47 | 41 / 47 | 24 / 26 | 20 / 21 | 44 / 47 | 163 / 188 |
| serious Total, serious adverse events | 3 / 49 | 0 / 47 | 1 / 47 | 2 / 47 | 3 / 141 | 6 / 190 | 3 / 47 | 7 / 47 | 9 / 47 | 5 / 26 | 5 / 21 | 10 / 47 | 29 / 188 |
Outcome results
Primary
Least Squares Mean Change From Baseline in ESSDAI Score at Week 24
The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) instrument contains 12 organ-specific domains contributing to disease activity. For each domain, features of disease activity are scored in 3 or 4 levels according to their severity. These scores are then summed across the 12 domains in a weighted manner to provide the total score ranging 0-123. Higher scores on the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) scale are associated with poorer health states. A negative change from baseline indicates improvement in disease status.
Time frame: Baseline, Week 24
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Up to Week 24) | Least Squares Mean Change From Baseline in ESSDAI Score at Week 24 | -6.39 Scores on a scale | Standard Error 0.808 |
| VAY736 - 5 mg (Up to Week 24) | Least Squares Mean Change From Baseline in ESSDAI Score at Week 24 | -5.64 Scores on a scale | Standard Error 0.85 |
| VAY736 - 50 mg (Up to Week 24) | Least Squares Mean Change From Baseline in ESSDAI Score at Week 24 | -6.93 Scores on a scale | Standard Error 0.836 |
| VAY736 - 300 mg (Up to Week 24) | Least Squares Mean Change From Baseline in ESSDAI Score at Week 24 | -8.30 Scores on a scale | Standard Error 0.828 |
Comparison: Week 24: VAY736 5 mg vs. Placebop-value: 0.516195% CI: [-1.52, 3.02]Mixed Models Analysis
Comparison: Week 24: VAY736 50 mg vs. Placebop-value: 0.633295% CI: [-2.8, 1.71]Mixed Models Analysis
Comparison: Week 24: VAY736 300 mg vs. Placebop-value: 0.092195% CI: [-4.15, 0.32]Mixed Models Analysis
Secondary
Kaplan-Meier Analysis for Time to Recovery to Baseline Like Values for B-cell Counts
B-cell counts were measured before, during and after treatment with VAY736. After stopping VAY736 treatment they were used to monitor patients for time to recovery of adequate CD19+ B cell counts prior to discharge from the study. Change from baseline in B-cell counts before, during and after treatment with VAY736 as well as the time to recover to baseline like values (defined as at least 80% of baseline counts or \>= 50 cells/μL) were analyzed by descriptive statistics. Baseline was defined as the last assessment performed on or prior to the date of administration of the first dose of study treatment.
Time frame: Up to two years from last dose patient received.
Population: Full analysis set (FAS): patients were analyzed according to the first treatment received (at Period 2, 24 weeks). VAY736 300 mg - Placebo included patients who discontinued in Period 2 and entered Period 4 directly and patients who completed Period 2 and were re-randomized to placebo. Only patients with baseline measurement and at least one measurement post-baseline were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (Up to Week 24) | Kaplan-Meier Analysis for Time to Recovery to Baseline Like Values for B-cell Counts | 3.8 months |
| VAY736 - 5 mg (Up to Week 24) | Kaplan-Meier Analysis for Time to Recovery to Baseline Like Values for B-cell Counts | 4.8 months |
| VAY736 - 50 mg (Up to Week 24) | Kaplan-Meier Analysis for Time to Recovery to Baseline Like Values for B-cell Counts | 6.8 months |
| VAY736 - 300 mg (Up to Week 24) | Kaplan-Meier Analysis for Time to Recovery to Baseline Like Values for B-cell Counts | 8.4 months |
| VAY736 300 mg - VAY736 300 mg | Kaplan-Meier Analysis for Time to Recovery to Baseline Like Values for B-cell Counts | 6.5 months |
Secondary
Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16
The SF36 includes 8 scale scores (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health) and two summary scores, the physical and mental component scores. The first four and last four scales comprise physical and mental component scores, respectively. The range of scores of the physical component (PCS) and mental component (MCS) is 0 (lowest or worst possible level of functioning) to 100 (highest or best possible level of functioning).
Time frame: Baseline, Weeks 4, 8, 12 and 16
Population: Full Analysis Set (FAS): Only participants with a value at both Baseline and post-baseline visit included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16 | Week 4 - Mental Component Score | 0.49 Scores on a scale | Standard Error 1.091 |
| Placebo (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16 | Week 8 - Mental Component Score | 2.65 Scores on a scale | Standard Error 2.267 |
| Placebo (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16 | Week 12 - Mental Component Score | 2.89 Scores on a scale | Standard Error 1.188 |
| Placebo (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16 | Week 16 - Mental Component Score | 4.60 Scores on a scale | Standard Error 1.214 |
| Placebo (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16 | Week 4 - Physical Component Score | 3.35 Scores on a scale | Standard Error 0.844 |
| Placebo (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16 | Week 8 - Physical Component Score | 3.83 Scores on a scale | Standard Error 0.894 |
| Placebo (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16 | Week 12 - Physical Component Score | 3.83 Scores on a scale | Standard Error 0.894 |
| Placebo (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16 | Week 16 - Physical Component Score | 4.72 Scores on a scale | Standard Error 0.968 |
| VAY736 - 5 mg (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16 | Week 8 - Physical Component Score | 4.56 Scores on a scale | Standard Error 0.949 |
| VAY736 - 5 mg (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16 | Week 4 - Physical Component Score | 3.94 Scores on a scale | Standard Error 0.889 |
| VAY736 - 5 mg (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16 | Week 8 - Mental Component Score | 3.80 Scores on a scale | Standard Error 1.341 |
| VAY736 - 5 mg (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16 | Week 16 - Physical Component Score | 4.67 Scores on a scale | Standard Error 1.02 |
| VAY736 - 5 mg (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16 | Week 12 - Physical Component Score | 4.56 Scores on a scale | Standard Error 0.949 |
| VAY736 - 5 mg (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16 | Week 16 - Mental Component Score | 3.00 Scores on a scale | Standard Error 1.281 |
| VAY736 - 5 mg (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16 | Week 12 - Mental Component Score | 5.42 Scores on a scale | Standard Error 1.264 |
| VAY736 - 5 mg (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16 | Week 4 - Mental Component Score | 1.89 Scores on a scale | Standard Error 1.151 |
| VAY736 - 50 mg (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16 | Week 12 - Physical Component Score | 3.48 Scores on a scale | Standard Error 0.941 |
| VAY736 - 50 mg (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16 | Week 12 - Mental Component Score | 3.94 Scores on a scale | Standard Error 1.265 |
| VAY736 - 50 mg (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16 | Week 16 - Mental Component Score | 5.57 Scores on a scale | Standard Error 1.291 |
| VAY736 - 50 mg (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16 | Week 4 - Physical Component Score | 1.14 Scores on a scale | Standard Error 0.878 |
| VAY736 - 50 mg (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16 | Week 8 - Physical Component Score | 3.48 Scores on a scale | Standard Error 0.941 |
| VAY736 - 50 mg (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16 | Week 16 - Physical Component Score | 3.32 Scores on a scale | Standard Error 1.021 |
| VAY736 - 50 mg (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16 | Week 4 - Mental Component Score | 2.46 Scores on a scale | Standard Error 1.149 |
| VAY736 - 50 mg (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16 | Week 8 - Mental Component Score | 4.65 Scores on a scale | Standard Error 1.363 |
| VAY736 - 300 mg (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16 | Week 12 - Mental Component Score | 4.59 Scores on a scale | Standard Error 1.207 |
| VAY736 - 300 mg (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16 | Week 16 - Mental Component Score | 5.46 Scores on a scale | Standard Error 1.247 |
| VAY736 - 300 mg (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16 | Week 8 - Mental Component Score | 3.35 Scores on a scale | Standard Error 1.294 |
| VAY736 - 300 mg (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16 | Week 4 - Mental Component Score | 2.18 Scores on a scale | Standard Error 1.116 |
| VAY736 - 300 mg (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16 | Week 4 - Physical Component Score | 1.98 Scores on a scale | Standard Error 0.863 |
| VAY736 - 300 mg (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16 | Week 16 - Physical Component Score | 4.57 Scores on a scale | Standard Error 0.993 |
| VAY736 - 300 mg (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16 | Week 12 - Physical Component Score | 3.47 Scores on a scale | Standard Error 0.909 |
| VAY736 - 300 mg (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16 | Week 8 - Physical Component Score | 3.47 Scores on a scale | Standard Error 0.909 |
Secondary
Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) Over 24 Weeks
The SF36 includes 8 scale scores (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health) and two summary scores, the physical and mental component scores. The first four and last four scales comprise physical and mental component scores, respectively. The range of scores of the physical component (PCS) and mental component (MCS) is 0 (lowest or worst possible level of functioning) to 100 (highest or best possible level of functioning).
Time frame: Baseline, Week 24
Population: Full analysis set (FAS)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) Over 24 Weeks | Mental Component Score | 4.63 Scores on a scale | Standard Error 1.259 |
| Placebo (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) Over 24 Weeks | Physical Component Score | 3.66 Scores on a scale | Standard Error 0.952 |
| VAY736 - 5 mg (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) Over 24 Weeks | Physical Component Score | 4.79 Scores on a scale | Standard Error 1.019 |
| VAY736 - 5 mg (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) Over 24 Weeks | Mental Component Score | 3.61 Scores on a scale | Standard Error 1.35 |
| VAY736 - 50 mg (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) Over 24 Weeks | Mental Component Score | 5.31 Scores on a scale | Standard Error 1.367 |
| VAY736 - 50 mg (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) Over 24 Weeks | Physical Component Score | 2.66 Scores on a scale | Standard Error 1.026 |
| VAY736 - 300 mg (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) Over 24 Weeks | Mental Component Score | 5.63 Scores on a scale | Standard Error 1.286 |
| VAY736 - 300 mg (Up to Week 24) | Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) Over 24 Weeks | Physical Component Score | 5.50 Scores on a scale | Standard Error 0.972 |
Comparison: Week 24: VAY736 5 mg vs. Placebo / Mental Component Scorep-value: 0.576895% CI: [-4.61, 2.57]Mixed Models Analysis
Comparison: Week 24: VAY736 50 mg vs. Placebo / Mental Component Scorep-value: 0.711395% CI: [-2.93, 4.28]Mixed Models Analysis
Comparison: Week 24: VAY736 300 mg vs. Placebo / Mental Component Scorep-value: 0.572295% CI: [-2.49, 4.48]Mixed Models Analysis
Comparison: Week 24: VAY736 5 mg vs. Placebo / Physical Component Scorep-value: 0.413895% CI: [-1.59, 3.83]Mixed Models Analysis
Comparison: Week 24: VAY736 50 mg vs. Placebo / Physical Component Scorep-value: 0.466395% CI: [-3.72, 1.71]Mixed Models Analysis
Comparison: Week 24: VAY736 300 mg vs. Placebo / Physical Component Scorep-value: 0.169495% CI: [-0.79, 4.47]Mixed Models Analysis
Secondary
Least Squares Mean Change From Baseline in ESSDAI Score at Weeks 4, 8, 12, and 16
The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) instrument contains 12 organ-specific domains contributing to disease activity. For each domain, features of disease activity are scored in 3 or 4 levels according to their severity. These scores are then summed across the 12 domains in a weighted manner to provide the total score ranging 0-123. Higher scores on the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) scale are associated with poorer health states. A negative change from baseline indicates improvement in disease status.
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16
Population: Full Analysis Set (FAS). Only participants with a value at both Baseline and post-baseline visit included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Up to Week 24) | Least Squares Mean Change From Baseline in ESSDAI Score at Weeks 4, 8, 12, and 16 | Week 4 | -3.73 Scores on a scale | Standard Error 0.626 |
| Placebo (Up to Week 24) | Least Squares Mean Change From Baseline in ESSDAI Score at Weeks 4, 8, 12, and 16 | Week 8 | -4.13 Scores on a scale | Standard Error 0.704 |
| Placebo (Up to Week 24) | Least Squares Mean Change From Baseline in ESSDAI Score at Weeks 4, 8, 12, and 16 | Week 12 | -5.45 Scores on a scale | Standard Error 0.721 |
| Placebo (Up to Week 24) | Least Squares Mean Change From Baseline in ESSDAI Score at Weeks 4, 8, 12, and 16 | Week 16 | -6.08 Scores on a scale | Standard Error 0.818 |
| VAY736 - 5 mg (Up to Week 24) | Least Squares Mean Change From Baseline in ESSDAI Score at Weeks 4, 8, 12, and 16 | Week 8 | -4.65 Scores on a scale | Standard Error 0.733 |
| VAY736 - 5 mg (Up to Week 24) | Least Squares Mean Change From Baseline in ESSDAI Score at Weeks 4, 8, 12, and 16 | Week 12 | -4.89 Scores on a scale | Standard Error 0.762 |
| VAY736 - 5 mg (Up to Week 24) | Least Squares Mean Change From Baseline in ESSDAI Score at Weeks 4, 8, 12, and 16 | Week 16 | -5.67 Scores on a scale | Standard Error 0.852 |
| VAY736 - 5 mg (Up to Week 24) | Least Squares Mean Change From Baseline in ESSDAI Score at Weeks 4, 8, 12, and 16 | Week 4 | -2.28 Scores on a scale | Standard Error 0.661 |
| VAY736 - 50 mg (Up to Week 24) | Least Squares Mean Change From Baseline in ESSDAI Score at Weeks 4, 8, 12, and 16 | Week 12 | -5.69 Scores on a scale | Standard Error 0.739 |
| VAY736 - 50 mg (Up to Week 24) | Least Squares Mean Change From Baseline in ESSDAI Score at Weeks 4, 8, 12, and 16 | Week 8 | -4.73 Scores on a scale | Standard Error 0.72 |
| VAY736 - 50 mg (Up to Week 24) | Least Squares Mean Change From Baseline in ESSDAI Score at Weeks 4, 8, 12, and 16 | Week 16 | -6.17 Scores on a scale | Standard Error 0.835 |
| VAY736 - 50 mg (Up to Week 24) | Least Squares Mean Change From Baseline in ESSDAI Score at Weeks 4, 8, 12, and 16 | Week 4 | -3.37 Scores on a scale | Standard Error 0.638 |
| VAY736 - 300 mg (Up to Week 24) | Least Squares Mean Change From Baseline in ESSDAI Score at Weeks 4, 8, 12, and 16 | Week 16 | -6.99 Scores on a scale | Standard Error 0.836 |
| VAY736 - 300 mg (Up to Week 24) | Least Squares Mean Change From Baseline in ESSDAI Score at Weeks 4, 8, 12, and 16 | Week 8 | -6.38 Scores on a scale | Standard Error 0.717 |
| VAY736 - 300 mg (Up to Week 24) | Least Squares Mean Change From Baseline in ESSDAI Score at Weeks 4, 8, 12, and 16 | Week 4 | -4.53 Scores on a scale | Standard Error 0.651 |
| VAY736 - 300 mg (Up to Week 24) | Least Squares Mean Change From Baseline in ESSDAI Score at Weeks 4, 8, 12, and 16 | Week 12 | -6.64 Scores on a scale | Standard Error 0.739 |
Secondary
Least Squares Mean Change From Baseline in ESSPRI Score at Week 24
The EULAR Sjörgen's Syndrome Patient Reported Index (ESSPRI) is an established disease outcome measure for Sjögren's syndrome that is calculated by averaging the scales for pain, fatigue and dryness. The total score is the mean score of the 3 scales and ranges between 0 and 10 with higher values indicating more severity of symptoms. A negative change from baseline is a favorable outcome.
Time frame: Baseline, Week 24
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Up to Week 24) | Least Squares Mean Change From Baseline in ESSPRI Score at Week 24 | -1.71 Scores on a scale | Standard Error 0.288 |
| VAY736 - 5 mg (Up to Week 24) | Least Squares Mean Change From Baseline in ESSPRI Score at Week 24 | -1.39 Scores on a scale | Standard Error 0.304 |
| VAY736 - 50 mg (Up to Week 24) | Least Squares Mean Change From Baseline in ESSPRI Score at Week 24 | -1.70 Scores on a scale | Standard Error 0.301 |
| VAY736 - 300 mg (Up to Week 24) | Least Squares Mean Change From Baseline in ESSPRI Score at Week 24 | -1.77 Scores on a scale | Standard Error 0.295 |
Comparison: Week 24: VAY736 5 mg vs. Placebop-value: 0.445795% CI: [-0.5, 1.13]Mixed Models Analysis
Comparison: Week 24: VAY736 50 mg vs. Placebop-value: 0.30195% CI: [-0.79, 0.82]Mixed Models Analysis
Comparison: Week 24: VAY736 300 mg vs. Placebop-value: 0.885895% CI: [-0.86, 0.74]Mixed Models Analysis
Secondary
Least Squares Mean Change From Baseline in ESSPRI Score at Weeks 4, 8, 12 and 16
The EULAR Sjörgen's Syndrome Patient Reported Index (ESSPRI) is an established disease outcome measure for Sjögren's syndrome that is calculated by averaging the scales for pain, fatigue and dryness. The total score is the mean score of the 3 scales and ranges between 0 and 10 with higher values indicating more severity of symptoms. A negative change from baseline is a favorable outcome.
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16
Population: Full Analysis Set (FAS). Only participants with a value at both Baseline and post-baseline visit included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Up to Week 24) | Least Squares Mean Change From Baseline in ESSPRI Score at Weeks 4, 8, 12 and 16 | Week 4 | -0.54 Scores on a scale | Standard Error 0.236 |
| Placebo (Up to Week 24) | Least Squares Mean Change From Baseline in ESSPRI Score at Weeks 4, 8, 12 and 16 | Week 8 | -0.94 Scores on a scale | Standard Error 0.242 |
| Placebo (Up to Week 24) | Least Squares Mean Change From Baseline in ESSPRI Score at Weeks 4, 8, 12 and 16 | Week 12 | -1.42 Scores on a scale | Standard Error 0.265 |
| Placebo (Up to Week 24) | Least Squares Mean Change From Baseline in ESSPRI Score at Weeks 4, 8, 12 and 16 | Week 16 | -1.77 Scores on a scale | Standard Error 0.263 |
| VAY736 - 5 mg (Up to Week 24) | Least Squares Mean Change From Baseline in ESSPRI Score at Weeks 4, 8, 12 and 16 | Week 8 | -0.84 Scores on a scale | Standard Error 0.255 |
| VAY736 - 5 mg (Up to Week 24) | Least Squares Mean Change From Baseline in ESSPRI Score at Weeks 4, 8, 12 and 16 | Week 12 | -1.36 Scores on a scale | Standard Error 0.279 |
| VAY736 - 5 mg (Up to Week 24) | Least Squares Mean Change From Baseline in ESSPRI Score at Weeks 4, 8, 12 and 16 | Week 16 | -1.27 Scores on a scale | Standard Error 0.275 |
| VAY736 - 5 mg (Up to Week 24) | Least Squares Mean Change From Baseline in ESSPRI Score at Weeks 4, 8, 12 and 16 | Week 4 | -0.67 Scores on a scale | Standard Error 0.247 |
| VAY736 - 50 mg (Up to Week 24) | Least Squares Mean Change From Baseline in ESSPRI Score at Weeks 4, 8, 12 and 16 | Week 12 | -1.44 Scores on a scale | Standard Error 0.273 |
| VAY736 - 50 mg (Up to Week 24) | Least Squares Mean Change From Baseline in ESSPRI Score at Weeks 4, 8, 12 and 16 | Week 8 | -1.06 Scores on a scale | Standard Error 0.251 |
| VAY736 - 50 mg (Up to Week 24) | Least Squares Mean Change From Baseline in ESSPRI Score at Weeks 4, 8, 12 and 16 | Week 16 | -1.55 Scores on a scale | Standard Error 0.271 |
| VAY736 - 50 mg (Up to Week 24) | Least Squares Mean Change From Baseline in ESSPRI Score at Weeks 4, 8, 12 and 16 | Week 4 | -0.80 Scores on a scale | Standard Error 0.241 |
| VAY736 - 300 mg (Up to Week 24) | Least Squares Mean Change From Baseline in ESSPRI Score at Weeks 4, 8, 12 and 16 | Week 16 | -1.55 Scores on a scale | Standard Error 0.27 |
| VAY736 - 300 mg (Up to Week 24) | Least Squares Mean Change From Baseline in ESSPRI Score at Weeks 4, 8, 12 and 16 | Week 8 | -1.8 Scores on a scale | Standard Error 0.248 |
| VAY736 - 300 mg (Up to Week 24) | Least Squares Mean Change From Baseline in ESSPRI Score at Weeks 4, 8, 12 and 16 | Week 4 | -0.88 Scores on a scale | Standard Error 0.242 |
| VAY736 - 300 mg (Up to Week 24) | Least Squares Mean Change From Baseline in ESSPRI Score at Weeks 4, 8, 12 and 16 | Week 12 | -1.23 Scores on a scale | Standard Error 0.27 |
Secondary
Least Squares Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F) Score at Weeks 4, 8, 12 and 16
The Functional Assessment of Chronic Illness Therapy-Fatigue Scale (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 previous week. The level of fatigue is measured on a four-point Likert scale (4 = not at all fatigued to 0 = very much fatigued). The global score ranges between 0 and 52, with higher scores indicating less fatigue.
Time frame: Baseline, Weeks 4, 8, 12 and 16
Population: Full Analysis Set (FAS). Only participants with a value at both Baseline and post-baseline visit included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Up to Week 24) | Least Squares Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F) Score at Weeks 4, 8, 12 and 16 | Week 4 | 3.78 Scores on a scale | Standard Deviation 1.175 |
| Placebo (Up to Week 24) | Least Squares Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F) Score at Weeks 4, 8, 12 and 16 | Week 8 | 5.49 Scores on a scale | Standard Deviation 1.222 |
| Placebo (Up to Week 24) | Least Squares Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F) Score at Weeks 4, 8, 12 and 16 | Week 12 | 6.25 Scores on a scale | Standard Deviation 1.349 |
| Placebo (Up to Week 24) | Least Squares Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F) Score at Weeks 4, 8, 12 and 16 | Week 16 | 8.56 Scores on a scale | Standard Deviation 1.284 |
| VAY736 - 5 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F) Score at Weeks 4, 8, 12 and 16 | Week 8 | 6.36 Scores on a scale | Standard Deviation 1.297 |
| VAY736 - 5 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F) Score at Weeks 4, 8, 12 and 16 | Week 12 | 8.17 Scores on a scale | Standard Deviation 1.429 |
| VAY736 - 5 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F) Score at Weeks 4, 8, 12 and 16 | Week 16 | 7.09 Scores on a scale | Standard Deviation 1.357 |
| VAY736 - 5 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F) Score at Weeks 4, 8, 12 and 16 | Week 4 | 6.32 Scores on a scale | Standard Deviation 1.239 |
| VAY736 - 50 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F) Score at Weeks 4, 8, 12 and 16 | Week 12 | 5.73 Scores on a scale | Standard Deviation 1.427 |
| VAY736 - 50 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F) Score at Weeks 4, 8, 12 and 16 | Week 8 | 3.93 Scores on a scale | Standard Deviation 1.303 |
| VAY736 - 50 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F) Score at Weeks 4, 8, 12 and 16 | Week 16 | 6.86 Scores on a scale | Standard Deviation 1.359 |
| VAY736 - 50 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F) Score at Weeks 4, 8, 12 and 16 | Week 4 | 3.12 Scores on a scale | Standard Deviation 1.229 |
| VAY736 - 300 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F) Score at Weeks 4, 8, 12 and 16 | Week 16 | 8.30 Scores on a scale | Standard Deviation 1.318 |
| VAY736 - 300 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F) Score at Weeks 4, 8, 12 and 16 | Week 8 | 5.98 Scores on a scale | Standard Deviation 1.25 |
| VAY736 - 300 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F) Score at Weeks 4, 8, 12 and 16 | Week 4 | 3.39 Scores on a scale | Standard Deviation 1.203 |
| VAY736 - 300 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F) Score at Weeks 4, 8, 12 and 16 | Week 12 | 6.05 Scores on a scale | Standard Deviation 1.374 |
Secondary
Least Squares Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F) Score Over 24 Weeks
The Functional Assessment of Chronic Illness Therapy-Fatigue Scale (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 previous week. The level of fatigue is measured on a four-point Likert scale (4 = not at all fatigued to 0 = very much fatigued). The global score ranges between 0 and 52, with higher scores indicating less fatigue.
Time frame: Baseline, Week 24
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Up to Week 24) | Least Squares Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F) Score Over 24 Weeks | 9.05 Scores on a scale | Standard Error 1.404 |
| VAY736 - 5 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F) Score Over 24 Weeks | 7.12 Scores on a scale | Standard Error 1.502 |
| VAY736 - 50 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F) Score Over 24 Weeks | 6.48 Scores on a scale | Standard Error 1.518 |
| VAY736 - 300 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F) Score Over 24 Weeks | 9.36 Scores on a scale | Standard Error 1.436 |
Comparison: Week 24: VAY736 5 mg vs. Placebop-value: 0.342495% CI: [-5.93, 2.07]Mixed Models Analysis
Comparison: Week 24: VAY736 50 mg vs. Placebop-value: 0.209295% CI: [-6.58, 1.45]Mixed Models Analysis
Comparison: Week 24: VAY736 300 mg vs. Placebop-value: 0.87495% CI: [-3.58, 4.2]Mixed Models Analysis
Secondary
Least Squares Mean Change From Baseline in Physician's Global Assessment (PhGA) of Patient's Overall Disease Activity Using Patient Visual Analog Scale (VAS) at Weeks 4, 8, 12 and 16
Physician global assessment of overall disease activity (PhGA) was performed using a 100 mm visual analogue scale (VAS) ranging from no disease activity (score 0) to maximal disease activity (score 100), after the question Considering all the ways the disease affects your patient, draw a line on the scale for how well his or her condition is today. A negative change from baseline is a favourable outcome.
Time frame: Baseline, Weeks 4, 8, 12 and 16
Population: Full Analysis Set (FAS). Only participants with a value at both Baseline and post-baseline visit included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Up to Week 24) | Least Squares Mean Change From Baseline in Physician's Global Assessment (PhGA) of Patient's Overall Disease Activity Using Patient Visual Analog Scale (VAS) at Weeks 4, 8, 12 and 16 | Week 4 | -12.49 Scores on a scale | Standard Error 2.327 |
| Placebo (Up to Week 24) | Least Squares Mean Change From Baseline in Physician's Global Assessment (PhGA) of Patient's Overall Disease Activity Using Patient Visual Analog Scale (VAS) at Weeks 4, 8, 12 and 16 | Week 8 | -18.54 Scores on a scale | Standard Error 2.239 |
| Placebo (Up to Week 24) | Least Squares Mean Change From Baseline in Physician's Global Assessment (PhGA) of Patient's Overall Disease Activity Using Patient Visual Analog Scale (VAS) at Weeks 4, 8, 12 and 16 | Week 12 | -21.01 Scores on a scale | Standard Error 2.299 |
| Placebo (Up to Week 24) | Least Squares Mean Change From Baseline in Physician's Global Assessment (PhGA) of Patient's Overall Disease Activity Using Patient Visual Analog Scale (VAS) at Weeks 4, 8, 12 and 16 | Week 16 | -19.44 Scores on a scale | Standard Error 2.572 |
| VAY736 - 5 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Physician's Global Assessment (PhGA) of Patient's Overall Disease Activity Using Patient Visual Analog Scale (VAS) at Weeks 4, 8, 12 and 16 | Week 8 | -16.53 Scores on a scale | Standard Error 2.338 |
| VAY736 - 5 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Physician's Global Assessment (PhGA) of Patient's Overall Disease Activity Using Patient Visual Analog Scale (VAS) at Weeks 4, 8, 12 and 16 | Week 12 | -20.72 Scores on a scale | Standard Error 2.413 |
| VAY736 - 5 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Physician's Global Assessment (PhGA) of Patient's Overall Disease Activity Using Patient Visual Analog Scale (VAS) at Weeks 4, 8, 12 and 16 | Week 16 | -24.49 Scores on a scale | Standard Error 2.687 |
| VAY736 - 5 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Physician's Global Assessment (PhGA) of Patient's Overall Disease Activity Using Patient Visual Analog Scale (VAS) at Weeks 4, 8, 12 and 16 | Week 4 | -10.50 Scores on a scale | Standard Error 2.445 |
| VAY736 - 50 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Physician's Global Assessment (PhGA) of Patient's Overall Disease Activity Using Patient Visual Analog Scale (VAS) at Weeks 4, 8, 12 and 16 | Week 12 | -25.35 Scores on a scale | Standard Error 2.341 |
| VAY736 - 50 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Physician's Global Assessment (PhGA) of Patient's Overall Disease Activity Using Patient Visual Analog Scale (VAS) at Weeks 4, 8, 12 and 16 | Week 8 | -22.12 Scores on a scale | Standard Error 2.374 |
| VAY736 - 50 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Physician's Global Assessment (PhGA) of Patient's Overall Disease Activity Using Patient Visual Analog Scale (VAS) at Weeks 4, 8, 12 and 16 | Week 16 | -24.77 Scores on a scale | Standard Error 2.676 |
| VAY736 - 50 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Physician's Global Assessment (PhGA) of Patient's Overall Disease Activity Using Patient Visual Analog Scale (VAS) at Weeks 4, 8, 12 and 16 | Week 4 | -12.38 Scores on a scale | Standard Error 2.361 |
| VAY736 - 300 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Physician's Global Assessment (PhGA) of Patient's Overall Disease Activity Using Patient Visual Analog Scale (VAS) at Weeks 4, 8, 12 and 16 | Week 16 | -25.77 Scores on a scale | Standard Error 2.633 |
| VAY736 - 300 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Physician's Global Assessment (PhGA) of Patient's Overall Disease Activity Using Patient Visual Analog Scale (VAS) at Weeks 4, 8, 12 and 16 | Week 8 | -24.85 Scores on a scale | Standard Error 2.289 |
| VAY736 - 300 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Physician's Global Assessment (PhGA) of Patient's Overall Disease Activity Using Patient Visual Analog Scale (VAS) at Weeks 4, 8, 12 and 16 | Week 4 | -18.67 Scores on a scale | Standard Error 2.367 |
| VAY736 - 300 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Physician's Global Assessment (PhGA) of Patient's Overall Disease Activity Using Patient Visual Analog Scale (VAS) at Weeks 4, 8, 12 and 16 | Week 12 | -27.25 Scores on a scale | Standard Error 2.305 |
Secondary
Least Squares Mean Change From Baseline in Physician's Global Assessment (PhGA) of Patient's Overall Disease Activity Using Patient Visual Analog Scale (VAS) Over 24 Weeks
Physician global assessment of overall disease activity (PhGA) was performed using a 100 mm visual analogue scale (VAS) ranging from no disease activity (score 0) to maximal disease activity (score 100), after the question Considering all the ways the disease affects your patient, draw a line on the scale for how well his or her condition is today. A negative change from baseline is a favourable outcome.
Time frame: Baseline, 24 weeks
Population: Full analysis set (FAS)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Up to Week 24) | Least Squares Mean Change From Baseline in Physician's Global Assessment (PhGA) of Patient's Overall Disease Activity Using Patient Visual Analog Scale (VAS) Over 24 Weeks | -23.64 Scores on a scale | Standard Error 2.601 |
| VAY736 - 5 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Physician's Global Assessment (PhGA) of Patient's Overall Disease Activity Using Patient Visual Analog Scale (VAS) Over 24 Weeks | -27.81 Scores on a scale | Standard Error 2.751 |
| VAY736 - 50 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Physician's Global Assessment (PhGA) of Patient's Overall Disease Activity Using Patient Visual Analog Scale (VAS) Over 24 Weeks | -28.13 Scores on a scale | Standard Error 2.7 |
| VAY736 - 300 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Physician's Global Assessment (PhGA) of Patient's Overall Disease Activity Using Patient Visual Analog Scale (VAS) Over 24 Weeks | -31.99 Scores on a scale | Standard Error 2.63 |
Comparison: Week 24: VAY736 5 mg vs. Placebop-value: 0.267195% CI: [-11.56, 3.22]Mixed Models Analysis
Comparison: Week 24: VAY736 50 mg vs. Placebop-value: 0.224895% CI: [-11.78, 2.79]Mixed Models Analysis
Comparison: Week 24: VAY736 300 mg vs. Placebop-value: 0.022495% CI: [-15.51, -1.2]Mixed Models Analysis
Secondary
Least Squares Mean Change From Baseline in Salivary Flow Rate at Week 24
Change from baseline in salivary flow rate (unstimulated and stimulated) at 24 weeks as compared to placebo. Unstimulated saliva is a mix of serous and mucous secretions coming primarily from the submandibular and minor salivary glands. The parotid gland produces the largest volume of stimulated saliva. Stimulated saliva accounts for 80-90% of daily salivary production.
Time frame: Baseline, 24 weeks
Population: Full analysis set (FAS): The overall number of participants analyzed represents the FAS. The number analyzed per row represents participants with data available at each assessment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Up to Week 24) | Least Squares Mean Change From Baseline in Salivary Flow Rate at Week 24 | Stimulated | 0.05 mL/min | Standard Error 0.067 |
| Placebo (Up to Week 24) | Least Squares Mean Change From Baseline in Salivary Flow Rate at Week 24 | Unstimulated | 0.00 mL/min | Standard Error 0.03 |
| VAY736 - 5 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Salivary Flow Rate at Week 24 | Unstimulated | 0.01 mL/min | Standard Error 0.034 |
| VAY736 - 5 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Salivary Flow Rate at Week 24 | Stimulated | 0.16 mL/min | Standard Error 0.074 |
| VAY736 - 50 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Salivary Flow Rate at Week 24 | Unstimulated | -0.00 mL/min | Standard Error 0.032 |
| VAY736 - 50 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Salivary Flow Rate at Week 24 | Stimulated | 0.18 mL/min | Standard Error 0.071 |
| VAY736 - 300 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Salivary Flow Rate at Week 24 | Unstimulated | -0.01 mL/min | Standard Error 0.031 |
| VAY736 - 300 mg (Up to Week 24) | Least Squares Mean Change From Baseline in Salivary Flow Rate at Week 24 | Stimulated | 0.25 mL/min | Standard Error 0.98 |
Comparison: Week 24: VAY736 5 mg vs. Placebo (Stimulated salivary flow rate)p-value: 0.27195% CI: [-0.08, 0.3]Mixed Models Analysis
Comparison: Week 24: VAY736 50 mg vs. Placebo (Stimulated salivary flow rate)p-value: 0.161895% CI: [-0.05, 0.32]Mixed Models Analysis
Comparison: Week 24: VAY736 300 mg vs. Placebo (Stimulated salivary flow rate)p-value: 0.037495% CI: [0.01, 0.38]Mixed Models Analysis
Comparison: Week 24: VAY736 5 mg vs. Placebo (Unstimulated salivary flow rate)p-value: 0.955995% CI: [-0.09, 0.09]Mixed Models Analysis
Comparison: Week 24: VAY736 50 mg vs. Placebo (Unstimulated salivary flow rate)p-value: 0.92995% CI: [-0.09, 0.08]Mixed Models Analysis
Comparison: Week 24: VAY736 300 mg vs. Placebo (Unstimulated salivary flow rate)p-value: 0.727695% CI: [-0.1, 0.07]Mixed Models Analysis
Secondary
Patient's Global Assessment (PaGA) Score at Weeks 4, 8, 12, 16 and 24
The PaGA of disease activity was performed using a 100 mm Visual Analog Scale (VAS) ranging from 0 (no disease activity) to 100 (maximal disease activity), in response to the question Considering all the ways Sjögren's syndrome affects you, please draw a line on the scale to indicate how well you are doing today. A negative change from baseline is a favourable outcome.
Time frame: Weeks 4, 8, 12, 16 and 24
Population: Full Analysis Set (FAS). Only participants with a value at both Baseline and post-baseline visit included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Up to Week 24) | Patient's Global Assessment (PaGA) Score at Weeks 4, 8, 12, 16 and 24 | Week 8 | -9.74 Scores on a scale | Standard Error 3.035 |
| Placebo (Up to Week 24) | Patient's Global Assessment (PaGA) Score at Weeks 4, 8, 12, 16 and 24 | Week 24 | -15.11 Scores on a scale | Standard Error 3.405 |
| Placebo (Up to Week 24) | Patient's Global Assessment (PaGA) Score at Weeks 4, 8, 12, 16 and 24 | Week 16 | -16.26 Scores on a scale | Standard Error 3.194 |
| Placebo (Up to Week 24) | Patient's Global Assessment (PaGA) Score at Weeks 4, 8, 12, 16 and 24 | Week 4 | -9.42 Scores on a scale | Standard Error 2.85 |
| Placebo (Up to Week 24) | Patient's Global Assessment (PaGA) Score at Weeks 4, 8, 12, 16 and 24 | Week 12 | -11.45 Scores on a scale | Standard Error 3.064 |
| VAY736 - 5 mg (Up to Week 24) | Patient's Global Assessment (PaGA) Score at Weeks 4, 8, 12, 16 and 24 | Week 4 | -10.02 Scores on a scale | Standard Error 2.992 |
| VAY736 - 5 mg (Up to Week 24) | Patient's Global Assessment (PaGA) Score at Weeks 4, 8, 12, 16 and 24 | Week 8 | -11.48 Scores on a scale | Standard Error 3.214 |
| VAY736 - 5 mg (Up to Week 24) | Patient's Global Assessment (PaGA) Score at Weeks 4, 8, 12, 16 and 24 | Week 12 | -17.51 Scores on a scale | Standard Error 3.244 |
| VAY736 - 5 mg (Up to Week 24) | Patient's Global Assessment (PaGA) Score at Weeks 4, 8, 12, 16 and 24 | Week 16 | -17.56 Scores on a scale | Standard Error 3.361 |
| VAY736 - 5 mg (Up to Week 24) | Patient's Global Assessment (PaGA) Score at Weeks 4, 8, 12, 16 and 24 | Week 24 | -12.83 Scores on a scale | Standard Error 3.648 |
| VAY736 - 50 mg (Up to Week 24) | Patient's Global Assessment (PaGA) Score at Weeks 4, 8, 12, 16 and 24 | Week 4 | -5.96 Scores on a scale | Standard Error 2.969 |
| VAY736 - 50 mg (Up to Week 24) | Patient's Global Assessment (PaGA) Score at Weeks 4, 8, 12, 16 and 24 | Week 12 | -11.73 Scores on a scale | Standard Error 3.234 |
| VAY736 - 50 mg (Up to Week 24) | Patient's Global Assessment (PaGA) Score at Weeks 4, 8, 12, 16 and 24 | Week 24 | -11.85 Scores on a scale | Standard Error 3.704 |
| VAY736 - 50 mg (Up to Week 24) | Patient's Global Assessment (PaGA) Score at Weeks 4, 8, 12, 16 and 24 | Week 16 | -14.86 Scores on a scale | Standard Error 3.375 |
| VAY736 - 50 mg (Up to Week 24) | Patient's Global Assessment (PaGA) Score at Weeks 4, 8, 12, 16 and 24 | Week 8 | -8.70 Scores on a scale | Standard Error 3.271 |
| VAY736 - 300 mg (Up to Week 24) | Patient's Global Assessment (PaGA) Score at Weeks 4, 8, 12, 16 and 24 | Week 8 | -15.27 Scores on a scale | Standard Error 3.091 |
| VAY736 - 300 mg (Up to Week 24) | Patient's Global Assessment (PaGA) Score at Weeks 4, 8, 12, 16 and 24 | Week 16 | -15.78 Scores on a scale | Standard Error 3.271 |
| VAY736 - 300 mg (Up to Week 24) | Patient's Global Assessment (PaGA) Score at Weeks 4, 8, 12, 16 and 24 | Week 12 | -13.57 Scores on a scale | Standard Error 3.105 |
| VAY736 - 300 mg (Up to Week 24) | Patient's Global Assessment (PaGA) Score at Weeks 4, 8, 12, 16 and 24 | Week 24 | -19.87 Scores on a scale | Standard Error 3.47 |
| VAY736 - 300 mg (Up to Week 24) | Patient's Global Assessment (PaGA) Score at Weeks 4, 8, 12, 16 and 24 | Week 4 | -8.96 Scores on a scale | Standard Error 2.906 |
Comparison: Week 24: VAY736 5 mg vs. Placebop-value: 0.645795% CI: [-7.46, 12]Mixed Models Analysis
Comparison: Week 24: VAY736 50 mg vs. Placebop-value: 0.513295% CI: [-6.55, 13.06]Mixed Models Analysis
Comparison: Week 24: VAY736 300 mg vs. Placebop-value: 9595% CI: [-14.21, 4.68]Mixed Models Analysis
Secondary
Peak Serum Concentration of VAY736
Pharmacokinetic Concentrations This outcome only applies to patients who received at least one dose of VAY739 (so not applicable to placebo)
Time frame: baseline to week 24, then week 28
Population: Safety set (SAF): included all patients who received at least one dose of study medication. Patients were analyzed according to treatment received and the actual stratum at baseline. The safety set was used in the analysis of all safety variables.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Up to Week 24) | Peak Serum Concentration of VAY736 | 0.0747 ug/mL | Standard Deviation 0.203 |
| VAY736 - 5 mg (Up to Week 24) | Peak Serum Concentration of VAY736 | 0.475 ug/mL | Standard Deviation 0.38 |
| VAY736 - 50 mg (Up to Week 24) | Peak Serum Concentration of VAY736 | 1.46 ug/mL | Standard Deviation 0.596 |
| VAY736 - 300 mg (Up to Week 24) | Peak Serum Concentration of VAY736 | 2.15 ug/mL | Standard Deviation 1.47 |
| VAY736 300 mg - VAY736 300 mg | Peak Serum Concentration of VAY736 | 1.94 ug/mL | Standard Deviation 1.53 |
Secondary
Percent Change From Baseline in Whole Blood CD19+ B-cell Counts.
B-cell counts were measured before, during and after treatment with VAY736. After stopping VAY736 treatment they were used to monitor patients for time to recovery of adequate CD19+ B cell counts prior to discharge from the study. Change from baseline in B-cell counts before, during and after treatment with VAY736 as well as the time to recover to baseline like values (defined as at least 80% of baseline counts or \>= 50 cells/μL) were analyzed by descriptive statistics. Baseline was defined as the last assessment performed on or prior to the date of administration of the first dose of study treatment.
Time frame: Baseline, Week 24, Week 28
Population: Full analysis set (FAS): patients were analyzed according to the first treatment received (at Period 2, 24 weeks). VAY736 300 mg - Placebo included patients who discontinued in Period 2 and entered Period 4 directly and patients who completed Period 2 and were re-randomized to placebo. Only patients with baseline measurement and at least one measurement post-baseline were included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Up to Week 24) | Percent Change From Baseline in Whole Blood CD19+ B-cell Counts. | Week 24 | -88.00 Percent change | Standard Error 5.784 |
| VAY736 - 5 mg (Up to Week 24) | Percent Change From Baseline in Whole Blood CD19+ B-cell Counts. | Week 24 | -99.07 Percent change | Standard Error 5.812 |
| VAY736 - 50 mg (Up to Week 24) | Percent Change From Baseline in Whole Blood CD19+ B-cell Counts. | Week 24 | 3.29 Percent change | Standard Error 5.674 |
| VAY736 - 50 mg (Up to Week 24) | Percent Change From Baseline in Whole Blood CD19+ B-cell Counts. | Week 28 | -97.06 Percent change | Standard Error 5.732 |
| VAY736 - 300 mg (Up to Week 24) | Percent Change From Baseline in Whole Blood CD19+ B-cell Counts. | Week 28 | -105.3 Percent change | Standard Error 9.145 |
| VAY736 - 300 mg (Up to Week 24) | Percent Change From Baseline in Whole Blood CD19+ B-cell Counts. | Week 24 | -103.0 Percent change | Standard Error 8.198 |
| VAY736 300 mg - VAY736 300 mg | Percent Change From Baseline in Whole Blood CD19+ B-cell Counts. | Week 28 | -91.80 Percent change | Standard Error 8.272 |
| VAY736 300 mg - VAY736 300 mg | Percent Change From Baseline in Whole Blood CD19+ B-cell Counts. | Week 24 | -94.20 Percent change | Standard Error 8.098 |