Safety and Efficacy of VAY736 in Patients With Primary Sj... | NCT02962895 | Trialant
NCT02962895
Sponsor
Novartis Pharmaceuticals
Status
Completed
Last Update Posted
Jan 7, 2025Actual
Enrollment
190Actual
Phase
Phase 2
Conditions
Primary Sjogren Syndrome
Interventions
VAY736
Placebo
Countries
United States
Argentina
Austria
Belgium
Chile
France
Germany
Hungary
Israel
Italy
Japan
Netherlands
Poland
Portugal
Romania
Russia
Spain
Taiwan
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT02962895
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
CVAY736A2201
Secondary IDs
Not provided
Brief Title
Safety and Efficacy of VAY736 in Patients With Primary Sjogren's Syndrome (pSS)
Official Title
Study of Safety and Efficacy of Multiple VAY736 Doses in Patients With Moderate to Severe Primary Sjogren's Syndrome (pSS)
Acronym
Not provided
Organization
NovartisINDUSTRY
Status Module
Record Verification Date
Jan 2025
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Jun 27, 2017Actual
Primary Completion Date
Jun 30, 2020Actual
Completion Date
Sep 23, 2021Actual
First Submitted Date
Nov 3, 2016
First Submission Date that Met QC Criteria
Nov 9, 2016
First Posted Date
Nov 15, 2016Estimated
Results Waived
Not provided
Results First Submitted Date
Jul 13, 2022
Results First Submitted that Met QC Criteria
Oct 28, 2024
Results First Posted Date
Oct 29, 2024Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Jul 16, 2020
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Oct 29, 2024Actual
Last Update Submitted Date
Jan 6, 2025
Last Update Posted Date
Jan 7, 2025Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Novartis PharmaceuticalsINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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.
Conditions Module
Conditions
Primary Sjogren Syndrome
Keywords
Sjogren
VAY736
ianalumab
pSS
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
190Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
VAY736 dose 1 - 5mg
Experimental
VAY736 low
Biological: VAY736
VAY736 dose 2 - 50mg
Experimental
VAY736 medium
Biological: VAY736
VAY736 dose 3 - 300 mg
Experimental
VAY736 high
Biological: VAY736
Placebo
Placebo Comparator
Placebo control
Other: Placebo
Interventions
Name
Type
Description
Arm Group Labels
Other Names
VAY736
Biological
VAY736
VAY736 dose 1 - 5mg
VAY736 dose 2 - 50mg
VAY736 dose 3 - 300 mg
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
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.
Baseline, Week 24
Secondary Outcomes
Measure
Description
Time Frame
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.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
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
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
75 Years
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Integral Rheumatology and Immunology Specialists IRIS
Bowman SJ, Fox R, Dorner T, Mariette X, Papas A, Grader-Beck T, Fisher BA, Barcelos F, De Vita S, Schulze-Koops H, Moots RJ, Junge G, Woznicki JN, Sopala MA, Luo WL, Hueber W. Safety and efficacy of subcutaneous ianalumab (VAY736) in patients with primary Sjogren's syndrome: a randomised, double-blind, placebo-controlled, phase 2b dose-finding trial. Lancet. 2022 Jan 8;399(10320):161-171. doi: 10.1016/S0140-6736(21)02251-0. Epub 2021 Nov 30.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
Plan to Share IPD
Yes
Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
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).
Recruitment Details
190 Patients were enrolled from 56 centers in 19 countries.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Placebo (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
FG001
VAY736 - 5 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
Periods
Title
Milestones
Reasons Not Completed
Period 2 (Randomized Set: Up to Week 24)
Type
Comment
Milestone Data
STARTED
All randomized patients were included in the Full Analysis Set (FAS) and Safety Set (SAF)
Baseline Characteristics Module
Baseline Analysis Population Description
Not provided
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Jan 16, 2020
Jul 13, 2022
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
Estimated Results First Submitted Date
Not provided
Condition Browse Module
No data available
No data is available for this block.
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
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.
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Triple
Masking Description
Not provided
Who Masked
ParticipantCare ProviderInvestigator
Ianalumab
Placebo
Other
Placebo control
Placebo
Baseline, Week 4, Week 8, Week 12, Week 16
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.
Baseline, Week 24
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.
Baseline, Week 4, Week 8, Week 12, Week 16
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.
Baseline, 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
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.
Baseline, Weeks 4, 8, 12 and 16
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).
Baseline, 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
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).
Baseline, Weeks 4, 8, 12 and 16
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.
Baseline, 24 weeks
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.
Baseline, Weeks 4, 8, 12 and 16
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.
Weeks 4, 8, 12, 16 and 24
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.
Baseline, 24 weeks
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.
Baseline, Week 24, Week 28
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.
Up to two years from last dose patient received.
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)
baseline to week 24, then week 28
Indianapolis
Indiana
46202
United States
The John Hopkins Jerome L Greene Sjogren
Baltimore
Maryland
21224
United States
Tufts School of Dental Medicine
Boston
Massachusetts
02111
United States
AAIR Research Center
Rochester
New York
14618
United States
UPMC
Pittsburgh
Pennsylvania
15213
United States
Advanced Rheumatology and Arthritis Wellness Center
Wexford
Pennsylvania
15090
United States
Baylor College Of Medicine
Houston
Texas
77030
United States
First Outpatient Research Unit
San Antonio
Texas
78229
United States
Novartis Investigative Site
Ciudad Autonoma de Bs As
Buenos Aires
C1055AAF
Argentina
Novartis Investigative Site
CABA
1117
Argentina
Novartis Investigative Site
Córdoba
5000
Argentina
Novartis Investigative Site
Córdoba
X5016KEH
Argentina
Novartis Investigative Site
Graz
8036
Austria
Novartis Investigative Site
Brussels
1070
Belgium
Novartis Investigative Site
Leuven
3000
Belgium
Novartis Investigative Site
Santiago
7500710
Chile
Novartis Investigative Site
Santiago
8207257
Chile
Novartis Investigative Site
Brest
29200
France
Novartis Investigative Site
Lille
59037
France
Novartis Investigative Site
Berlin
13353
Germany
Novartis Investigative Site
Freiburg im Breisgau
79106
Germany
Novartis Investigative Site
München
81377
Germany
Novartis Investigative Site
Würzburg
97080
Germany
Novartis Investigative Site
Budapest
H-1097
Hungary
Novartis Investigative Site
Szeged
6720
Hungary
Novartis Investigative Site
Ramat Gan
52621
Israel
Novartis Investigative Site
Rozzano
MI
20089
Italy
Novartis Investigative Site
Roma
RM
00161
Italy
Novartis Investigative Site
Udine
UD
33100
Italy
Novartis Investigative Site
Nagoya
Aichi-ken
457 8510
Japan
Novartis Investigative Site
Sasebo
Nagasaki
857-1165
Japan
Novartis Investigative Site
Itabashi-ku
Tokyo
173-8610
Japan
Novartis Investigative Site
Shinjuku-ku
Tokyo
160 8582
Japan
Novartis Investigative Site
Rotterdam
South Holland
3015 GD
Netherlands
Novartis Investigative Site
Lublin
20-954
Poland
Novartis Investigative Site
Almada
2801 951
Portugal
Novartis Investigative Site
Lisbon
1050-034
Portugal
Novartis Investigative Site
Lisbon
1649 035
Portugal
Novartis Investigative Site
Porto
4099-001
Portugal
Novartis Investigative Site
Brasov
500283
Romania
Novartis Investigative Site
Cluj-Napoca
400006
Romania
Novartis Investigative Site
Moscow
115522
Russia
Novartis Investigative Site
Orenburg
460000
Russia
Novartis Investigative Site
Saint Petersburg
195257
Russia
Novartis Investigative Site
Yekaterinburg
620028
Russia
Novartis Investigative Site
Vigo
Pontevedra
36200
Spain
Novartis Investigative Site
San Cristóbal de La Laguna
Santa Cruz De Tenerife
38320
Spain
Novartis Investigative Site
Barcelona
08041
Spain
Novartis Investigative Site
Kaohsiung City
81346
Taiwan
Novartis Investigative Site
Taichung
40447
Taiwan
Novartis Investigative Site
Taichung
407219
Taiwan
Novartis Investigative Site
Taipei
11490
Taiwan
Novartis Investigative Site
Birmingham
B15 2TH
United Kingdom
Novartis Investigative Site
Liverpool
L9 7AL
United Kingdom
Novartis Investigative Site
Southend
SSO 0RY
United Kingdom
FG002
VAY736 - 50 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
FG003
VAY736 - 300 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
FG004
VAY736 - 150 mg
Placebo patients in Period 2 switched to VAY736 - 150 mg s.c. administration every 4 weeks in Period 3 (Period 3 = 28 weeks)
FG005
VAY736 300 mg - Placebo
VAY736 300 mg patients in Period 2 re-randomized to Placebo every 4 weeks in Period 3 (Period 3 = 28 weeks)
FG006
VAY736 300 mg - VAY736 300 mg
VAY736 300 mg patients in Period 2 re-randomized to VAY736 300 mg every 4 weeks in Period 3 (Period 3 = 28 weeks)
FG00049 subjects
FG00147 subjects
FG00247 subjects
FG00347 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
COMPLETED
FG00047 subjects
FG00142 subjects
FG00243 subjects
FG00346 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
NOT COMPLETED
FG0002 subjects
FG0015 subjects
FG0024 subjects
FG0031 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
Type
Comment
Reasons
Withdrawal by Subject
FG0001 subjects
FG0011 subjects
FG0022 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
Withdrawal of Informed Consent
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Adverse Event
FG0000 subjects
FG0012 subjects
FG0022 subjects
FG0030 subjects
FG004
New therapy for indication
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Non-compliance with treatment
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Pregnancy
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
Period 3 (Randomized Set / Weeks: 24-52)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG00447 subjects
FG00522 subjects
FG00621 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Patient/guardian decision
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Period 4 (Safety Follow-Up)
Type
Comment
Milestone Data
STARTED
FG0002 subjects
FG00147 subjects
FG00247 subjects
FG0034 subjects
FG00446 subjects
FG00522 subjects
FG00620 subjects
COMPLETED
FG0002 subjects
FG00141 subjects
FG00243 subjects
FG0031 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0016 subjects
FG0024 subjects
FG0033 subjects
FG004
Type
Comment
Reasons
Lack of Efficacy
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG003
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Placebo (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
BG001
VAY736 - 5 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
BG002
VAY736 - 50 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
BG003
VAY736 - 300 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
BG004
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00049
BG00147
BG00247
BG00347
BG004190
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
Years
Title
Denominators
Categories
Title
Measurements
BG00047.9± 12.44
BG00152.5± 13.64
BG00251.0± 11.12
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00047
BG00146
BG002
Race/Ethnicity, Customized
Number
Participants
Title
Denominators
Categories
Asian
Title
Measurements
BG0004
BG0013
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
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.
Full Analysis Set (FAS)
Posted
Least Squares Mean
Standard Error
Scores on a scale
Baseline, Week 24
ID
Title
Description
OG000
Placebo (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
OG001
VAY736 - 5 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
OG002
VAY736 - 50 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
OG003
VAY736 - 300 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
Units
Counts
Participants
OG00049
OG00147
OG00247
OG003
Title
Denominators
Categories
Title
Measurements
OG000-6.39± 0.808
OG001-5.64± 0.850
OG002-6.93± 0.836
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Week 24: VAY736 5 mg vs. Placebo
Mixed Models Analysis
Confidence intervals and p-values derived from a mixed model for repeated measures (MMRM)
0.5161
Least Squares Mean Difference
0.75
2-Sided
95
-1.52
3.02
Superiority
OG000
OG002
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.
Full Analysis Set (FAS). Only participants with a value at both Baseline and post-baseline visit included.
Posted
Least Squares Mean
Standard Error
Scores on a scale
Baseline, Week 4, Week 8, Week 12, Week 16
ID
Title
Description
OG000
Placebo (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
OG001
VAY736 - 5 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
OG002
VAY736 - 50 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
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.
Full Analysis Set (FAS)
Posted
Least Squares Mean
Standard Error
Scores on a scale
Baseline, Week 24
ID
Title
Description
OG000
Placebo (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
OG001
VAY736 - 5 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
OG002
VAY736 - 50 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
OG003
VAY736 - 300 mg (Up to Week 24)
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.
Full Analysis Set (FAS). Only participants with a value at both Baseline and post-baseline visit included.
Posted
Least Squares Mean
Standard Error
Scores on a scale
Baseline, Week 4, Week 8, Week 12, Week 16
ID
Title
Description
OG000
Placebo (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
OG001
VAY736 - 5 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
OG002
VAY736 - 50 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
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.
Full Analysis Set (FAS)
Posted
Least Squares Mean
Standard Error
Scores on a scale
Baseline, Week 24
ID
Title
Description
OG000
Placebo (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
OG001
VAY736 - 5 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
OG002
VAY736 - 50 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
OG003
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.
Full Analysis Set (FAS). Only participants with a value at both Baseline and post-baseline visit included.
Posted
Mean
Standard Deviation
Scores on a scale
Baseline, Weeks 4, 8, 12 and 16
ID
Title
Description
OG000
Placebo (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
OG001
VAY736 - 5 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
OG002
VAY736 - 50 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
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).
Full analysis set (FAS)
Posted
Least Squares Mean
Standard Error
Scores on a scale
Baseline, Week 24
ID
Title
Description
OG000
Placebo (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
OG001
VAY736 - 5 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
OG002
VAY736 - 50 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
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).
Full Analysis Set (FAS): Only participants with a value at both Baseline and post-baseline visit included.
Posted
Least Squares Mean
Standard Error
Scores on a scale
Baseline, Weeks 4, 8, 12 and 16
ID
Title
Description
OG000
Placebo (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
OG001
VAY736 - 5 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
OG002
VAY736 - 50 mg (Up to Week 24)
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.
Full analysis set (FAS)
Posted
Least Squares Mean
Standard Error
Scores on a scale
Baseline, 24 weeks
ID
Title
Description
OG000
Placebo (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
OG001
VAY736 - 5 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
OG002
VAY736 - 50 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
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.
Full Analysis Set (FAS). Only participants with a value at both Baseline and post-baseline visit included.
Posted
Least Squares Mean
Standard Error
Scores on a scale
Baseline, Weeks 4, 8, 12 and 16
ID
Title
Description
OG000
Placebo (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
OG001
VAY736 - 5 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
OG002
VAY736 - 50 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
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.
Full Analysis Set (FAS). Only participants with a value at both Baseline and post-baseline visit included.
Posted
Least Squares Mean
Standard Error
Scores on a scale
Weeks 4, 8, 12, 16 and 24
ID
Title
Description
OG000
Placebo (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
OG001
VAY736 - 5 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
OG002
VAY736 - 50 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
OG003
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.
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.
Posted
Least Squares Mean
Standard Error
mL/min
Baseline, 24 weeks
ID
Title
Description
OG000
Placebo (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
OG001
VAY736 - 5 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
OG002
VAY736 - 50 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
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.
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.
Posted
Least Squares Mean
Standard Error
Percent change
Baseline, Week 24, Week 28
ID
Title
Description
OG000
VAY736 - 5 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
OG001
VAY736 - 50 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
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.
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.
Posted
Median
95% Confidence Interval
months
Up to two years from last dose patient received.
ID
Title
Description
OG000
VAY736 - 5 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
OG001
VAY736 - 50 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
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)
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.
Posted
Mean
Standard Deviation
ug/mL
baseline to week 24, then week 28
ID
Title
Description
OG000
VAY736 - 5 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
OG001
VAY736 - 50 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
OG002
VAY736 - 300 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
OG003
VAY736 300 mg - Placebo
Time Frame
From first dose of study drug until end of follow-up period, up to approximately 3 years (max duration of follow-up was 2 years).
Description
An adverse event is any sign or symptom that occurs during the conduct of the trial and safety follow-up.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Placebo (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
0
49
3
49
33
49
EG001
VAY736 - 5 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
0
47
0
47
40
47
EG002
VAY736 - 50 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
0
47
1
47
34
47
EG003
VAY736 - 300 mg (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
0
47
2
47
41
47
EG004
Any VAY736 (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
0
141
3
141
115
141
EG005
ALL (Up to Week 24)
Period 2 (Double blind Placebo s.c. administration every 4 weeks (q4w) for a 24-week period)
0
190
6
190
148
190
EG006
VAY736 - 5 mg 24 Weeks (Periods 2 and 4)
All events reported from start of VAY736 - 5 mg dose in Period 2 (blinded treatment period of 24 weeks) and in the post treatment safety follow-up (Period 4)
0
47
3
47
41
47
EG007
VAY736 - 50 mg 24 Weeks (Periods 2 and 4)
All events reported from start of VAY736 - 50 mg dose in Period 2 (blinded treatment period of 24 weeks) and in the post treatment safety follow-up (Period 4)
0
47
7
47
37
47
EG008
VAY736 - 150 mg 28 Weeks (Periods 3 and 4)
All events reported from start of VAY736 - 150 mg dose in Period 3 (extended blinded treatment period of 28 weeks) up to the end of post treatment safety follow-up (Period 4)
0
47
9
47
41
47
EG009
VAY736 - 300 mg 24 Weeks (Entire Study)
All events reported from the beginning of the study up until the end of post treatment safety follow-up (Period 4)
0
26
5
26
24
26
EG010
VAY736 - 300 mg 52 Weeks (Entire Study)
All events reported from the beginning of the study up until the end of post treatment safety follow-up (Period 4)
0
21
5
21
20
21
EG011
Any VAY736 - 300 mg (Periods 2, 3 and 4)
All events reported from the beginning of the study up until the end of post treatment safety follow-up (Period 4)
0
47
10
47
44
47
EG012
Any VAY736 (Periods 2, 3 and 4)
All events reported from the beginning of the study up until the end of post treatment safety follow-up (Period 4)
0
188
29
188
163
188
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG0030 affected47 at risk
EG0040 affected141 at risk
EG0050 affected190 at risk
EG0060 affected47 at risk
EG0070 affected47 at risk
EG0080 affected47 at risk
EG0091 affected26 at risk
EG0100 affected21 at risk
EG0111 affected47 at risk
EG0121 affected188 at risk
Leukopenia
Blood and lymphatic system disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Deafness neurosensory
Ear and labyrinth disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Pancreatic disorder
Gastrointestinal disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Cholelithiasis
Hepatobiliary disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Cell-mediated immune deficiency
Immune system disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Appendicitis
Infections and infestations
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0021 affected47 at risk
EG003
Bronchitis
Infections and infestations
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
COVID-19
Infections and infestations
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
COVID-19 pneumonia
Infections and infestations
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Candida infection
Infections and infestations
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA (24.0)
Systematic Assessment
EG0001 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Pneumonia
Infections and infestations
MedDRA (24.0)
Systematic Assessment
EG0001 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Respiratory syncytial virus bronchiolitis
Infections and infestations
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Sinusitis
Infections and infestations
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Tubo-ovarian abscess
Infections and infestations
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0021 affected47 at risk
EG003
Wound infection
Infections and infestations
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Femoral neck fracture
Injury, poisoning and procedural complications
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Forearm fracture
Injury, poisoning and procedural complications
MedDRA (24.0)
Systematic Assessment
EG0001 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Injection related reaction
Injury, poisoning and procedural complications
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Thoracic vertebral fracture
Injury, poisoning and procedural complications
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Traumatic fracture
Injury, poisoning and procedural complications
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Weight decreased
Investigations
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Osteoarthritis
Musculoskeletal and connective tissue disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Sjogren's syndrome
Musculoskeletal and connective tissue disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Breast cancer metastatic
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Extranodal marginal zone B-cell lymphoma (MALT type)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Migraine
Nervous system disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Seizure
Nervous system disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Syncope
Nervous system disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Device breakage
Product Issues
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Renal colic
Renal and urinary disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Pulmonary embolism
Respiratory, thoracic and mediastinal disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Vasculitis
Vascular disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Iron deficiency anaemia
Blood and lymphatic system disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0021 affected47 at risk
EG0030 affected47 at risk
EG004
Leukopenia
Blood and lymphatic system disorders
MedDRA (24.0)
Systematic Assessment
EG0002 affected49 at risk
EG0013 affected47 at risk
EG0022 affected47 at risk
EG003
Lymphopenia
Blood and lymphatic system disorders
MedDRA (24.0)
Systematic Assessment
EG0003 affected49 at risk
EG0012 affected47 at risk
EG0024 affected47 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA (24.0)
Systematic Assessment
EG0001 affected49 at risk
EG0013 affected47 at risk
EG0021 affected47 at risk
EG003
Vertigo
Ear and labyrinth disorders
MedDRA (24.0)
Systematic Assessment
EG0001 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA (24.0)
Systematic Assessment
EG0004 affected49 at risk
EG0013 affected47 at risk
EG0022 affected47 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0011 affected47 at risk
EG0020 affected47 at risk
EG003
Gastrooesophageal reflux disease
Gastrointestinal disorders
MedDRA (24.0)
Systematic Assessment
EG0001 affected49 at risk
EG0011 affected47 at risk
EG0023 affected47 at risk
EG003
Mouth ulceration
Gastrointestinal disorders
MedDRA (24.0)
Systematic Assessment
EG0001 affected49 at risk
EG0011 affected47 at risk
EG0020 affected47 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0011 affected47 at risk
EG0021 affected47 at risk
EG003
Asthenia
General disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Influenza like illness
General disorders
MedDRA (24.0)
Systematic Assessment
EG0001 affected49 at risk
EG0010 affected47 at risk
EG0023 affected47 at risk
EG003
Injection site reaction
General disorders
MedDRA (24.0)
Systematic Assessment
EG0002 affected49 at risk
EG0014 affected47 at risk
EG0029 affected47 at risk
EG003
Oedema peripheral
General disorders
MedDRA (24.0)
Systematic Assessment
EG0002 affected49 at risk
EG0010 affected47 at risk
EG0022 affected47 at risk
EG003
Pyrexia
General disorders
MedDRA (24.0)
Systematic Assessment
EG0001 affected49 at risk
EG0010 affected47 at risk
EG0021 affected47 at risk
EG003
Acute sinusitis
Infections and infestations
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0011 affected47 at risk
EG0020 affected47 at risk
EG003
Bronchitis
Infections and infestations
MedDRA (24.0)
Systematic Assessment
EG0002 affected49 at risk
EG0013 affected47 at risk
EG0022 affected47 at risk
EG003
Conjunctivitis
Infections and infestations
MedDRA (24.0)
Systematic Assessment
EG0003 affected49 at risk
EG0013 affected47 at risk
EG0022 affected47 at risk
EG003
Cystitis
Infections and infestations
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0021 affected47 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0022 affected47 at risk
EG003
Influenza
Infections and infestations
MedDRA (24.0)
Systematic Assessment
EG0001 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA (24.0)
Systematic Assessment
EG0005 affected49 at risk
EG0014 affected47 at risk
EG0022 affected47 at risk
EG003
Oral candidiasis
Infections and infestations
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Oral herpes
Infections and infestations
MedDRA (24.0)
Systematic Assessment
EG0001 affected49 at risk
EG0013 affected47 at risk
EG0021 affected47 at risk
EG003
Parotitis
Infections and infestations
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0011 affected47 at risk
EG0020 affected47 at risk
EG003
Sinusitis
Infections and infestations
MedDRA (24.0)
Systematic Assessment
EG0004 affected49 at risk
EG0014 affected47 at risk
EG0022 affected47 at risk
EG003
Tracheobronchitis
Infections and infestations
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0011 affected47 at risk
EG0020 affected47 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA (24.0)
Systematic Assessment
EG0004 affected49 at risk
EG0014 affected47 at risk
EG0025 affected47 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA (24.0)
Systematic Assessment
EG0004 affected49 at risk
EG0016 affected47 at risk
EG0022 affected47 at risk
EG003
Viral upper respiratory tract infection
Infections and infestations
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0011 affected47 at risk
EG0021 affected47 at risk
EG003
Animal bite
Injury, poisoning and procedural complications
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Arthropod bite
Injury, poisoning and procedural complications
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0021 affected47 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Injection related reaction
Injury, poisoning and procedural complications
MedDRA (24.0)
Systematic Assessment
EG0002 affected49 at risk
EG0016 affected47 at risk
EG0025 affected47 at risk
EG003
Wound
Injury, poisoning and procedural complications
MedDRA (24.0)
Systematic Assessment
EG0001 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Blood creatinine increased
Investigations
MedDRA (24.0)
Systematic Assessment
EG0002 affected49 at risk
EG0012 affected47 at risk
EG0021 affected47 at risk
EG003
Lymphocyte count decreased
Investigations
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0014 affected47 at risk
EG0020 affected47 at risk
EG003
Neutrophil count decreased
Investigations
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0013 affected47 at risk
EG0020 affected47 at risk
EG003
White blood cell count decreased
Investigations
MedDRA (24.0)
Systematic Assessment
EG0001 affected49 at risk
EG0013 affected47 at risk
EG0021 affected47 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA (24.0)
Systematic Assessment
EG0005 affected49 at risk
EG0013 affected47 at risk
EG0021 affected47 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (24.0)
Systematic Assessment
EG0003 affected49 at risk
EG0011 affected47 at risk
EG0024 affected47 at risk
EG003
Joint swelling
Musculoskeletal and connective tissue disorders
MedDRA (24.0)
Systematic Assessment
EG0001 affected49 at risk
EG0012 affected47 at risk
EG0020 affected47 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0022 affected47 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA (24.0)
Systematic Assessment
EG0001 affected49 at risk
EG0012 affected47 at risk
EG0020 affected47 at risk
EG003
Osteoarthritis
Musculoskeletal and connective tissue disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0012 affected47 at risk
EG0022 affected47 at risk
EG003
Sjogren's syndrome
Musculoskeletal and connective tissue disorders
MedDRA (24.0)
Systematic Assessment
EG0001 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Dizziness
Nervous system disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0011 affected47 at risk
EG0020 affected47 at risk
EG003
Headache
Nervous system disorders
MedDRA (24.0)
Systematic Assessment
EG0007 affected49 at risk
EG0014 affected47 at risk
EG0024 affected47 at risk
EG003
Polyneuropathy
Nervous system disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA (24.0)
Systematic Assessment
EG0001 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Dysuria
Renal and urinary disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA (24.0)
Systematic Assessment
EG0001 affected49 at risk
EG0012 affected47 at risk
EG0020 affected47 at risk
EG003
Nasal congestion
Respiratory, thoracic and mediastinal disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Productive cough
Respiratory, thoracic and mediastinal disorders
MedDRA (24.0)
Systematic Assessment
EG0001 affected49 at risk
EG0010 affected47 at risk
EG0020 affected47 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA (24.0)
Systematic Assessment
EG0001 affected49 at risk
EG0011 affected47 at risk
EG0021 affected47 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA (24.0)
Systematic Assessment
EG0003 affected49 at risk
EG0014 affected47 at risk
EG0022 affected47 at risk
EG003
Hypertension
Vascular disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected49 at risk
EG0011 affected47 at risk
EG0022 affected47 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.