PD of VAY736 in Patients With Primary Sjögren's Syndrome

A Single Dose, Double-blind, Placebo-controlled, Parallel Study to Assess the Pharmacodynamics, Pharmacokinetics and Safety and Tolerability of VAY736 in Patients With Primary Sjögren's Syndrome

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02149420

Acronym

CVAY736X2201

Enrollment

Registered

2014-05-29

Start date

2014-05-23

Completion date

2018-02-07

Last updated

2021-10-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Primary Sjögren's Syndrome

Keywords

primary Sjögren's syndrome, pharmacodynamics

Brief summary

This study was designed to evaluate the safety, tolerability, pharmacokinetics and therapeutic efficacy of a single intravenous infusion of VAY7346 monoclonal antibody in pSS patients

Detailed description

Patients were enrolled in 2 sequential cohorts: Cohort 1: 6 patients received 3 mg/kg or Placebo (2:1 ratio) Cohort 2: 21 patients received 10 mg/kg, 3 mg/kg or Placebo (6:1:3 ratio) At week 24 the blind was broken to assess continuation in the trial: * If a patient received VAY736 and their B cell recovery was demonstrated at Week 24, then patients completed the trial. * If a patient received VAY736 and their B cell recovery was NOT demonstrated at Week 24, then patients were followed up until B cell recovery was demonstrated * If a patient received placebo, they were offered the option of receiving open-label VAY736 (10 mg/kg) in a separate treatment arm.

Interventions

DRUGVAY736

DRUGPlacebo

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Masking description

Treatment was unblinded at an individual patient level at Week 24 to determine their progress in the study (follow-up, open-label VAY736 or End of Study Visit).

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

Inclusion criteria

* Fulfilled revised European US consensus criteria for pSS * ESSDAI value ≥ 6 * Elevated serum titers at screening of ANA (≥ 1:160) * Seropositive at screening for anti-SSA and/or anti-SSB antibodies * Stimulated whole salivary flow rate at screening of \> 0 mL/min

Exclusion criteria

\- Prior or previous use of (specific dosages and intervals prior to study start may apply): B-cell depleting therapy (e.g., rituximab), Prednisone, anti-BAFF mAb, CTLA4-Fc Ig (abatacept), anti-TNF-α mAb, cyclophosphamide, azathioprine and medications known to cause dry mouth. Hydroxychloroquine or methotrexate in a consistent dose for ≥ 3 months prior to randomization is allowed * Active or recent history of clinically significant infection * Vaccination within 2 month prior to study * History of primary or secondary immunodeficiency

Design outcomes

Primary

Measure	Time frame	Description
Change in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI)	Baseline, week 12	The effect of VAY736 on clinical disease activity was measured by the change in ESSDAI (EULAR Sjögren's syndrome disease activity index) between baseline and week 12. The 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 (range 0-123). A reduction from baseline indicates improvement in patients.
Overall Incidence of Adverse Events	Baseline to Week 24	Number of subjects with Adverse Events during the double blind treatment period.

Secondary

Measure	Time frame	Description
Change in Multidimensional Fatigue Inventory (MFI)	Baseline, week 12	The MFI is a patient self-reported outcome measure (questionnaires) to assess fatigue covering the following dimensions: General Fatigue, Physical Fatigue, Mental Fatigue, Reduced Motivation and Reduced Activity. Each dimension has a posible range from 4-20. A reduction from baseline in MFI indicates improvement.
Change in the Physician's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)	Baseline, week 12	The visual analogue scale used is a 100 mm VAS ranging from no disease (0 mm) to maximal disease activity (100 mm).
Change in the Patient's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)	Baseline, week 12	The visual analogue scale used is a 100 mm VAS ranging from no disease (0 mm) to maximal disease activity (100 mm).
VAY736 Serum Concentration - AUCinf	0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.	The area under the serum concentration-time curve from time zero to infinity \[mass × time / volume\]. The concentration of VAY736 was measured in the serum.
VAY736 Serum Concentration - AUClast	0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.	The area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration \[mass × time / volume\]. The concentration of VAY736 was measured in the serum.
Change in EULAR Sjögren's Syndrome Patient Response Index (ESSPRI)	Baseline, week 12	The ESSPRI is a patient self-reported outcome measure to assess dryness, limb pain, fatigue and mental fatigue, where each of the domains normally reported as 0 (not at all) to 10 (extremely severe). The final ESSPRI score is the average of three: dryness, pain and fatigue. A reduction from baseline indicates the improvement of symptoms. During the study all individual scores were reported as 1 to 10 instead. A linear transformation was reported to map the scores to the range of 0-10.
VAY736 Serum Concentration - Cmax	0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.	The observed maximum serum concentration following drug administration \[mass / volume\]. The concentration of VAY736 was measured in the serum.
VAY736 Serum Concentration - T1/2	0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.	Apparent terminal half-life, determined as the ln2/lambda\_z or 0.693/lambda\_z. The concentration of VAY736 was measured in the serum.
VAY736 Serum Concentration - Tmax	0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.	The time to reach the maximum concentration after drug administration \[time\]. The concentration of VAY736 was measured in the serum.
VAY736 Serum Concentration - Vz	0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.	The volume of distribution during the terminal elimination phase following intravenous administration \[volume\]. The concentration of VAY736 was measured in the serum.
VAY736 Serum Concentration - CL	0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.	The systemic (or total body) clearance from serum following intravenous administration \[volume / time\]. The concentration of VAY736 was measured in the serum.
Change in Short Form (36) Health Survey (SF-36)	Baseline, week 12	The SF-36 is a 36-item, patient self-reported outcome measure (questionnaires) of patient health. The outcome of the questionnaires in eight scales results in two summary scores, physical component and mental component, both ranging from 0 - 100. An increase from baseline in either component summary score indicates reduced disease burden.

Countries

Germany

Participant flow

Recruitment details

A total of 27 patients were enrolled and randomized into the study at one site in Germany.

Pre-assignment details

The patients were enrolled in 2 sequential cohorts: Cohort 1: Six patients were randomized to receive a single dose iv of VAY736 at a dose of 3mg/kg or placebo at a 2:1 ratio. Cohort 2: Twenty one patients were randomized to receive a single iv dose of VAY736 at a dose of 10.0 mg/kg or 3.0 mg/kg or placebo at a 6:1:3 ratio.

Participants by arm

Arm	Count
Placebo single dose iv of Placebo	9
VAY736 3 mg/kg single dose iv of VAY736 at a dose of 3mg/kg	6
VAY736 10 mg/kg single dose iv of VAY736 at a dose of 10mg/kg	12
Total	27

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Core Study	Administrative problems	0	1	2
Open Label VAY736 10 mg/kg Extension	Administrative problems	1	0	0

Baseline characteristics

Characteristic	Placebo	VAY736 3 mg/kg	VAY736 10 mg/kg	Total
Age, Continuous	46.7 Years STANDARD_DEVIATION 11.29	46.8 Years STANDARD_DEVIATION 8.75	55.3 Years STANDARD_DEVIATION 13.35	50.5 Years STANDARD_DEVIATION 12.16
Race/Ethnicity, Customized Caucasian	9 Participants	6 Participants	12 Participants	27 Participants
Sex: Female, Male Female	7 Participants	5 Participants	11 Participants	23 Participants
Sex: Female, Male Male	2 Participants	1 Participants	1 Participants	4 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	0 / 9	0 / 6	0 / 12	0 / 5
other Total, other adverse events	9 / 9	6 / 6	11 / 12	5 / 5
serious Total, serious adverse events	1 / 9	2 / 6	0 / 12	1 / 5

Outcome results

Primary

Change in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI)

The effect of VAY736 on clinical disease activity was measured by the change in ESSDAI (EULAR Sjögren's syndrome disease activity index) between baseline and week 12. The 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 (range 0-123). A reduction from baseline indicates improvement in patients.

Time frame: Baseline, week 12

Population: PD analysis set

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Change in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI)	Baseline	11.1 units on a scale	Standard Deviation 4.08
Placebo	Change in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI)	Change from Baseline to Week 12	-0.9 units on a scale	Standard Deviation 2.98
Placebo	Change in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI)	Week 12	10.2 units on a scale	Standard Deviation 5.29
VAY736 3 mg/kg	Change in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI)	Baseline	14.5 units on a scale	Standard Deviation 9.44
VAY736 3 mg/kg	Change in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI)	Change from Baseline to Week 12	-3.8 units on a scale	Standard Deviation 8.66
VAY736 3 mg/kg	Change in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI)	Week 12	10.7 units on a scale	Standard Deviation 7.69
VAY736 10 mg/kg	Change in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI)	Week 12	10.0 units on a scale	Standard Deviation 5.36
VAY736 10 mg/kg	Change in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI)	Baseline	11.5 units on a scale	Standard Deviation 4.38
VAY736 10 mg/kg	Change in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI)	Change from Baseline to Week 12	-1.5 units on a scale	Standard Deviation 3
VAY736 Combined	Change in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI)	Baseline	12.5 units on a scale	Standard Deviation 6.38
VAY736 Combined	Change in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI)	Change from Baseline to Week 12	-2.3 units on a scale	Standard Deviation 5.4
VAY736 Combined	Change in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI)	Week 12	10.2 units on a scale	Standard Deviation 6.01

Comparison: Per protocol the primary analysis was between placebo and the combined VAY736 groups at Week 12.p-value: 0.67895% CI: [-5.007, 3.18]repeated measures Bayesian analysis

Primary

Overall Incidence of Adverse Events

Number of subjects with Adverse Events during the double blind treatment period.

Time frame: Baseline to Week 24

Population: Safety analysis set

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Placebo	Overall Incidence of Adverse Events	Subjects with AEs post 24hr of infusion	8 Participants
Placebo	Overall Incidence of Adverse Events	Subjects with Study drug-related AEs	5 Participants
Placebo	Overall Incidence of Adverse Events	Subjects with AEs	8 Participants
Placebo	Overall Incidence of Adverse Events	Subjects with AEs within 24hr of infusion	2 Participants
Placebo	Overall Incidence of Adverse Events	Subjects with Infusion related AEs	1 Participants
VAY736 3 mg/kg	Overall Incidence of Adverse Events	Subjects with AEs post 24hr of infusion	6 Participants
VAY736 3 mg/kg	Overall Incidence of Adverse Events	Subjects with Study drug-related AEs	6 Participants
VAY736 3 mg/kg	Overall Incidence of Adverse Events	Subjects with AEs within 24hr of infusion	6 Participants
VAY736 3 mg/kg	Overall Incidence of Adverse Events	Subjects with AEs	6 Participants
VAY736 3 mg/kg	Overall Incidence of Adverse Events	Subjects with Infusion related AEs	6 Participants
VAY736 10 mg/kg	Overall Incidence of Adverse Events	Subjects with AEs post 24hr of infusion	8 Participants
VAY736 10 mg/kg	Overall Incidence of Adverse Events	Subjects with AEs	11 Participants
VAY736 10 mg/kg	Overall Incidence of Adverse Events	Subjects with AEs within 24hr of infusion	11 Participants
VAY736 10 mg/kg	Overall Incidence of Adverse Events	Subjects with Study drug-related AEs	11 Participants
VAY736 10 mg/kg	Overall Incidence of Adverse Events	Subjects with Infusion related AEs	9 Participants
VAY736 Combined	Overall Incidence of Adverse Events	Subjects with Study drug-related AEs	17 Participants
VAY736 Combined	Overall Incidence of Adverse Events	Subjects with AEs within 24hr of infusion	17 Participants
VAY736 Combined	Overall Incidence of Adverse Events	Subjects with AEs	17 Participants
VAY736 Combined	Overall Incidence of Adverse Events	Subjects with AEs post 24hr of infusion	14 Participants
VAY736 Combined	Overall Incidence of Adverse Events	Subjects with Infusion related AEs	15 Participants

Secondary

Change in EULAR Sjögren's Syndrome Patient Response Index (ESSPRI)

The ESSPRI is a patient self-reported outcome measure to assess dryness, limb pain, fatigue and mental fatigue, where each of the domains normally reported as 0 (not at all) to 10 (extremely severe). The final ESSPRI score is the average of three: dryness, pain and fatigue. A reduction from baseline indicates the improvement of symptoms. During the study all individual scores were reported as 1 to 10 instead. A linear transformation was reported to map the scores to the range of 0-10.

Time frame: Baseline, week 12

Population: PD analysis set

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Change in EULAR Sjögren's Syndrome Patient Response Index (ESSPRI)	Baseline	5.967 units on a scale	Standard Deviation 2.2179
Placebo	Change in EULAR Sjögren's Syndrome Patient Response Index (ESSPRI)	Change from Baseline to Week 12	-0.041 units on a scale	Standard Deviation 1.7805
Placebo	Change in EULAR Sjögren's Syndrome Patient Response Index (ESSPRI)	Week 12	5.926 units on a scale	Standard Deviation 1.5822
VAY736 3 mg/kg	Change in EULAR Sjögren's Syndrome Patient Response Index (ESSPRI)	Week 12	6.173 units on a scale	Standard Deviation 1.4753
VAY736 3 mg/kg	Change in EULAR Sjögren's Syndrome Patient Response Index (ESSPRI)	Baseline	6.049 units on a scale	Standard Deviation 1.2759
VAY736 3 mg/kg	Change in EULAR Sjögren's Syndrome Patient Response Index (ESSPRI)	Change from Baseline to Week 12	0.123 units on a scale	Standard Deviation 1.012
VAY736 10 mg/kg	Change in EULAR Sjögren's Syndrome Patient Response Index (ESSPRI)	Change from Baseline to Week 12	-1.667 units on a scale	Standard Deviation 1.8918
VAY736 10 mg/kg	Change in EULAR Sjögren's Syndrome Patient Response Index (ESSPRI)	Baseline	6.235 units on a scale	Standard Deviation 1.5379
VAY736 10 mg/kg	Change in EULAR Sjögren's Syndrome Patient Response Index (ESSPRI)	Week 12	4.568 units on a scale	Standard Deviation 2.5966

Secondary

Change in Multidimensional Fatigue Inventory (MFI)

The MFI is a patient self-reported outcome measure (questionnaires) to assess fatigue covering the following dimensions: General Fatigue, Physical Fatigue, Mental Fatigue, Reduced Motivation and Reduced Activity. Each dimension has a posible range from 4-20. A reduction from baseline in MFI indicates improvement.

Time frame: Baseline, week 12

Population: PD analysis set

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Change in Multidimensional Fatigue Inventory (MFI)	Physical Fatigue: Change from Baseline	-0.7 units on a scale	Standard Deviation 1.32
Placebo	Change in Multidimensional Fatigue Inventory (MFI)	General Fatigue: Change from Baseline	-1.2 units on a scale	Standard Deviation 1.64
Placebo	Change in Multidimensional Fatigue Inventory (MFI)	Reduced motivation: Week 12	12.0 units on a scale	Standard Deviation 5.32
Placebo	Change in Multidimensional Fatigue Inventory (MFI)	Mental Fatigue: Baseline	11.9 units on a scale	Standard Deviation 4.78
Placebo	Change in Multidimensional Fatigue Inventory (MFI)	General Fatigue: Week 12	12.8 units on a scale	Standard Deviation 4.84
Placebo	Change in Multidimensional Fatigue Inventory (MFI)	Reduced motivation: Baseline	12.4 units on a scale	Standard Deviation 4.93
Placebo	Change in Multidimensional Fatigue Inventory (MFI)	Mental Fatigue: Week 12	11.7 units on a scale	Standard Deviation 4.12
Placebo	Change in Multidimensional Fatigue Inventory (MFI)	Reduced activity: Baseline	11.8 units on a scale	Standard Deviation 2.86
Placebo	Change in Multidimensional Fatigue Inventory (MFI)	Mental Fatigue: Change from Baseline	-0.2 units on a scale	Standard Deviation 2.95
Placebo	Change in Multidimensional Fatigue Inventory (MFI)	Physical Fatigue: Baseline	12.9 units on a scale	Standard Deviation 4.14
Placebo	Change in Multidimensional Fatigue Inventory (MFI)	Reduced activity: Change from Baseline	-1.3 units on a scale	Standard Deviation 1.8
Placebo	Change in Multidimensional Fatigue Inventory (MFI)	General Fatigue: Baseline	14.0 units on a scale	Standard Deviation 4.72
Placebo	Change in Multidimensional Fatigue Inventory (MFI)	Physical Fatigue: Week 12	12.2 units on a scale	Standard Deviation 3.99
Placebo	Change in Multidimensional Fatigue Inventory (MFI)	Reduced activity: Week 12	10.4 units on a scale	Standard Deviation 3.81
Placebo	Change in Multidimensional Fatigue Inventory (MFI)	Reduced motivation: Change from Baseline	-0.4 units on a scale	Standard Deviation 2.4
VAY736 3 mg/kg	Change in Multidimensional Fatigue Inventory (MFI)	Reduced motivation: Change from Baseline	-2.3 units on a scale	Standard Deviation 4.5
VAY736 3 mg/kg	Change in Multidimensional Fatigue Inventory (MFI)	General Fatigue: Baseline	17.0 units on a scale	Standard Deviation 2.37
VAY736 3 mg/kg	Change in Multidimensional Fatigue Inventory (MFI)	General Fatigue: Week 12	14.2 units on a scale	Standard Deviation 6.4
VAY736 3 mg/kg	Change in Multidimensional Fatigue Inventory (MFI)	General Fatigue: Change from Baseline	-2.8 units on a scale	Standard Deviation 5.04
VAY736 3 mg/kg	Change in Multidimensional Fatigue Inventory (MFI)	Physical Fatigue: Baseline	15.7 units on a scale	Standard Deviation 2.34
VAY736 3 mg/kg	Change in Multidimensional Fatigue Inventory (MFI)	Physical Fatigue: Week 12	11.2 units on a scale	Standard Deviation 5.15
VAY736 3 mg/kg	Change in Multidimensional Fatigue Inventory (MFI)	Physical Fatigue: Change from Baseline	-4.5 units on a scale	Standard Deviation 6.57
VAY736 3 mg/kg	Change in Multidimensional Fatigue Inventory (MFI)	Mental Fatigue: Baseline	14.3 units on a scale	Standard Deviation 3.78
VAY736 3 mg/kg	Change in Multidimensional Fatigue Inventory (MFI)	Mental Fatigue: Week 12	11.3 units on a scale	Standard Deviation 4.18
VAY736 3 mg/kg	Change in Multidimensional Fatigue Inventory (MFI)	Mental Fatigue: Change from Baseline	-3.0 units on a scale	Standard Deviation 6.07
VAY736 3 mg/kg	Change in Multidimensional Fatigue Inventory (MFI)	Reduced motivation: Baseline	12.3 units on a scale	Standard Deviation 3.93
VAY736 3 mg/kg	Change in Multidimensional Fatigue Inventory (MFI)	Reduced motivation: Week 12	10.0 units on a scale	Standard Deviation 4.52
VAY736 3 mg/kg	Change in Multidimensional Fatigue Inventory (MFI)	Reduced activity: Baseline	10.8 units on a scale	Standard Deviation 1.72
VAY736 3 mg/kg	Change in Multidimensional Fatigue Inventory (MFI)	Reduced activity: Week 12	8.7 units on a scale	Standard Deviation 3.61
VAY736 3 mg/kg	Change in Multidimensional Fatigue Inventory (MFI)	Reduced activity: Change from Baseline	-2.2 units on a scale	Standard Deviation 4.83
VAY736 10 mg/kg	Change in Multidimensional Fatigue Inventory (MFI)	Physical Fatigue: Change from Baseline	-3.8 units on a scale	Standard Deviation 4.77
VAY736 10 mg/kg	Change in Multidimensional Fatigue Inventory (MFI)	Reduced activity: Week 12	9.3 units on a scale	Standard Deviation 5.08
VAY736 10 mg/kg	Change in Multidimensional Fatigue Inventory (MFI)	Reduced motivation: Week 12	9.8 units on a scale	Standard Deviation 4.97
VAY736 10 mg/kg	Change in Multidimensional Fatigue Inventory (MFI)	Physical Fatigue: Week 12	10.4 units on a scale	Standard Deviation 4.66
VAY736 10 mg/kg	Change in Multidimensional Fatigue Inventory (MFI)	Physical Fatigue: Baseline	14.2 units on a scale	Standard Deviation 3.41
VAY736 10 mg/kg	Change in Multidimensional Fatigue Inventory (MFI)	Reduced motivation: Change from Baseline	-1.1 units on a scale	Standard Deviation 4.56
VAY736 10 mg/kg	Change in Multidimensional Fatigue Inventory (MFI)	General Fatigue: Change from Baseline	-3.5 units on a scale	Standard Deviation 4.12
VAY736 10 mg/kg	Change in Multidimensional Fatigue Inventory (MFI)	General Fatigue: Baseline	15.9 units on a scale	Standard Deviation 3.34
VAY736 10 mg/kg	Change in Multidimensional Fatigue Inventory (MFI)	Reduced activity: Baseline	12.2 units on a scale	Standard Deviation 2.69
VAY736 10 mg/kg	Change in Multidimensional Fatigue Inventory (MFI)	Mental Fatigue: Week 12	9.8 units on a scale	Standard Deviation 5.17
VAY736 10 mg/kg	Change in Multidimensional Fatigue Inventory (MFI)	General Fatigue: Week 12	12.4 units on a scale	Standard Deviation 3.99
VAY736 10 mg/kg	Change in Multidimensional Fatigue Inventory (MFI)	Mental Fatigue: Change from Baseline	-3.2 units on a scale	Standard Deviation 5.84
VAY736 10 mg/kg	Change in Multidimensional Fatigue Inventory (MFI)	Mental Fatigue: Baseline	13.0 units on a scale	Standard Deviation 3.28
VAY736 10 mg/kg	Change in Multidimensional Fatigue Inventory (MFI)	Reduced activity: Change from Baseline	-2.9 units on a scale	Standard Deviation 4.25
VAY736 10 mg/kg	Change in Multidimensional Fatigue Inventory (MFI)	Reduced motivation: Baseline	10.9 units on a scale	Standard Deviation 2.68

Secondary

Change in Short Form (36) Health Survey (SF-36)

The SF-36 is a 36-item, patient self-reported outcome measure (questionnaires) of patient health. The outcome of the questionnaires in eight scales results in two summary scores, physical component and mental component, both ranging from 0 - 100. An increase from baseline in either component summary score indicates reduced disease burden.

Time frame: Baseline, week 12

Population: PD analysis set

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Change in Short Form (36) Health Survey (SF-36)	Physical component score: Baseline	46.886 units on a scale	Standard Deviation 6.3905
Placebo	Change in Short Form (36) Health Survey (SF-36)	Physical component score: Week 12	44.788 units on a scale	Standard Deviation 8.3513
Placebo	Change in Short Form (36) Health Survey (SF-36)	Physical component score: Change from Baseline	-2.098 units on a scale	Standard Deviation 7.9084
Placebo	Change in Short Form (36) Health Survey (SF-36)	Mental component score: Baseline	36.913 units on a scale	Standard Deviation 15.2776
Placebo	Change in Short Form (36) Health Survey (SF-36)	Mental component score: Week 12	41.012 units on a scale	Standard Deviation 13.2991
Placebo	Change in Short Form (36) Health Survey (SF-36)	Mental component score: Change from Baseline	4.099 units on a scale	Standard Deviation 5.3361
VAY736 3 mg/kg	Change in Short Form (36) Health Survey (SF-36)	Mental component score: Change from Baseline	2.653 units on a scale	Standard Deviation 17.1261
VAY736 3 mg/kg	Change in Short Form (36) Health Survey (SF-36)	Physical component score: Baseline	39.445 units on a scale	Standard Deviation 4.2857
VAY736 3 mg/kg	Change in Short Form (36) Health Survey (SF-36)	Mental component score: Baseline	37.517 units on a scale	Standard Deviation 6.8994
VAY736 3 mg/kg	Change in Short Form (36) Health Survey (SF-36)	Mental component score: Week 12	40.170 units on a scale	Standard Deviation 11.9815
VAY736 3 mg/kg	Change in Short Form (36) Health Survey (SF-36)	Physical component score: Week 12	45.493 units on a scale	Standard Deviation 7.306
VAY736 3 mg/kg	Change in Short Form (36) Health Survey (SF-36)	Physical component score: Change from Baseline	6.048 units on a scale	Standard Deviation 4.7189
VAY736 10 mg/kg	Change in Short Form (36) Health Survey (SF-36)	Physical component score: Week 12	47.671 units on a scale	Standard Deviation 9.2804
VAY736 10 mg/kg	Change in Short Form (36) Health Survey (SF-36)	Physical component score: Change from Baseline	1.656 units on a scale	Standard Deviation 5.4113
VAY736 10 mg/kg	Change in Short Form (36) Health Survey (SF-36)	Mental component score: Change from Baseline	3.073 units on a scale	Standard Deviation 11.5823
VAY736 10 mg/kg	Change in Short Form (36) Health Survey (SF-36)	Mental component score: Baseline	43.628 units on a scale	Standard Deviation 11.3667
VAY736 10 mg/kg	Change in Short Form (36) Health Survey (SF-36)	Physical component score: Baseline	46.015 units on a scale	Standard Deviation 9.3533
VAY736 10 mg/kg	Change in Short Form (36) Health Survey (SF-36)	Mental component score: Week 12	46.700 units on a scale	Standard Deviation 11.3182

Secondary

Change in the Patient's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)

The visual analogue scale used is a 100 mm VAS ranging from no disease (0 mm) to maximal disease activity (100 mm).

Time frame: Baseline, week 12

Population: PD analysis set

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Change in the Patient's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)	Week 12	55.2 units on a scale	Standard Deviation 21.57
Placebo	Change in the Patient's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)	Baseline	56.2 units on a scale	Standard Deviation 24.86
Placebo	Change in the Patient's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)	Change from Baseline to Week 12	-1.0 units on a scale	Standard Deviation 17.71
VAY736 3 mg/kg	Change in the Patient's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)	Week 12	44.2 units on a scale	Standard Deviation 22.75
VAY736 3 mg/kg	Change in the Patient's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)	Baseline	67.2 units on a scale	Standard Deviation 13.69
VAY736 3 mg/kg	Change in the Patient's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)	Change from Baseline to Week 12	-23.0 units on a scale	Standard Deviation 25.73
VAY736 10 mg/kg	Change in the Patient's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)	Baseline	59.8 units on a scale	Standard Deviation 24.3
VAY736 10 mg/kg	Change in the Patient's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)	Change from Baseline to Week 12	-19.0 units on a scale	Standard Deviation 21.08
VAY736 10 mg/kg	Change in the Patient's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)	Week 12	40.8 units on a scale	Standard Deviation 20.49

Secondary

Change in the Physician's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)

The visual analogue scale used is a 100 mm VAS ranging from no disease (0 mm) to maximal disease activity (100 mm).

Time frame: Baseline, week 12

Population: PD analysis set

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Change in the Physician's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)	Week 12	59.8 units on a scale	Standard Deviation 23.35
Placebo	Change in the Physician's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)	Baseline	57.3 units on a scale	Standard Deviation 17.73
Placebo	Change in the Physician's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)	Change from Baseline to Week 12	2.4 units on a scale	Standard Deviation 12.21
VAY736 3 mg/kg	Change in the Physician's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)	Week 12	43.0 units on a scale	Standard Deviation 23.82
VAY736 3 mg/kg	Change in the Physician's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)	Baseline	66.2 units on a scale	Standard Deviation 17.53
VAY736 3 mg/kg	Change in the Physician's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)	Change from Baseline to Week 12	-23.2 units on a scale	Standard Deviation 31.1
VAY736 10 mg/kg	Change in the Physician's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)	Baseline	65.0 units on a scale	Standard Deviation 11.74
VAY736 10 mg/kg	Change in the Physician's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)	Change from Baseline to Week 12	-16.5 units on a scale	Standard Deviation 18.96
VAY736 10 mg/kg	Change in the Physician's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)	Week 12	48.5 units on a scale	Standard Deviation 17.33

Secondary

VAY736 Serum Concentration - AUCinf

The area under the serum concentration-time curve from time zero to infinity \[mass × time / volume\]. The concentration of VAY736 was measured in the serum.