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NCT02149420: CVAY736X2201

PD of VAY736 in Patients With Primary Sjögren's Syndrome

Completed Phase 2 Results posted Last updated 4 October 2021
What this trial tests

Phase 2 trial testing VAY736 in Primary Sjögren's Syndrome in 27 participants. Completed in 7 February 2018.

Timeline
23 May 2014
Primary endpoint
7 February 2018
7 February 2018

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment27
Start date23 May 2014
Primary completion7 February 2018
Estimated completion7 February 2018
Sites1 location across Germany

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

Adults 18 to 75, any sex, with Primary Sjögren's Syndrome. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

Baseline
GroupValue95% CI
Placebo11.1± 4.08
VAY736 3 mg/kg14.5± 9.44
VAY736 10 mg/kg11.5± 4.38
VAY736 Combined12.5± 6.38
Week 12
GroupValue95% CI
Placebo10.2± 5.29
VAY736 3 mg/kg10.7± 7.69
VAY736 10 mg/kg10.0± 5.36
VAY736 Combined10.2± 6.01
Change from Baseline to Week 12
GroupValue95% CI
Placebo-0.9± 2.98
VAY736 3 mg/kg-3.8± 8.66
VAY736 10 mg/kg-1.5± 3.00
VAY736 Combined-2.3± 5.40
Change in EULAR Sjögren's Syndrome Patient Response Index (ESSPRI) Secondary · 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.

Baseline
GroupValue95% CI
Placebo5.967± 2.2179
VAY736 3 mg/kg6.049± 1.2759
VAY736 10 mg/kg6.235± 1.5379
Week 12
GroupValue95% CI
Placebo5.926± 1.5822
VAY736 3 mg/kg6.173± 1.4753
VAY736 10 mg/kg4.568± 2.5966
Change from Baseline to Week 12
GroupValue95% CI
Placebo-0.041± 1.7805
VAY736 3 mg/kg0.123± 1.0120
VAY736 10 mg/kg-1.667± 1.8918
Change in Short Form (36) Health Survey (SF-36) Secondary · 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.

Physical component score: Baseline
GroupValue95% CI
Placebo46.886± 6.3905
VAY736 3 mg/kg39.445± 4.2857
VAY736 10 mg/kg46.015± 9.3533
Physical component score: Week 12
GroupValue95% CI
Placebo44.788± 8.3513
VAY736 3 mg/kg45.493± 7.3060
VAY736 10 mg/kg47.671± 9.2804
Physical component score: Change from Baseline
GroupValue95% CI
Placebo-2.098± 7.9084
VAY736 3 mg/kg6.048± 4.7189
VAY736 10 mg/kg1.656± 5.4113
Mental component score: Baseline
GroupValue95% CI
Placebo36.913± 15.2776
VAY736 3 mg/kg37.517± 6.8994
VAY736 10 mg/kg43.628± 11.3667
Mental component score: Week 12
GroupValue95% CI
Placebo41.012± 13.2991
VAY736 3 mg/kg40.170± 11.9815
VAY736 10 mg/kg46.700± 11.3182
Mental component score: Change from Baseline
GroupValue95% CI
Placebo4.099± 5.3361
VAY736 3 mg/kg2.653± 17.1261
VAY736 10 mg/kg3.073± 11.5823
Change in Multidimensional Fatigue Inventory (MFI) Secondary · 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.

General Fatigue: Baseline
GroupValue95% CI
Placebo14.0± 4.72
VAY736 3 mg/kg17.0± 2.37
VAY736 10 mg/kg15.9± 3.34
General Fatigue: Week 12
GroupValue95% CI
Placebo12.8± 4.84
VAY736 3 mg/kg14.2± 6.40
VAY736 10 mg/kg12.4± 3.99
General Fatigue: Change from Baseline
GroupValue95% CI
Placebo-1.2± 1.64
VAY736 3 mg/kg-2.8± 5.04
VAY736 10 mg/kg-3.5± 4.12
Physical Fatigue: Baseline
GroupValue95% CI
Placebo12.9± 4.14
VAY736 3 mg/kg15.7± 2.34
VAY736 10 mg/kg14.2± 3.41
Physical Fatigue: Week 12
GroupValue95% CI
Placebo12.2± 3.99
VAY736 3 mg/kg11.2± 5.15
VAY736 10 mg/kg10.4± 4.66
Physical Fatigue: Change from Baseline
GroupValue95% CI
Placebo-0.7± 1.32
VAY736 3 mg/kg-4.5± 6.57
VAY736 10 mg/kg-3.8± 4.77
Mental Fatigue: Baseline
GroupValue95% CI
Placebo11.9± 4.78
VAY736 3 mg/kg14.3± 3.78
VAY736 10 mg/kg13.0± 3.28
Mental Fatigue: Week 12
GroupValue95% CI
Placebo11.7± 4.12
VAY736 3 mg/kg11.3± 4.18
VAY736 10 mg/kg9.8± 5.17
Change in the Physician's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS) Secondary · 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).

Baseline
GroupValue95% CI
Placebo57.3± 17.73
VAY736 3 mg/kg66.2± 17.53
VAY736 10 mg/kg65.0± 11.74
Week 12
GroupValue95% CI
Placebo59.8± 23.35
VAY736 3 mg/kg43.0± 23.82
VAY736 10 mg/kg48.5± 17.33
Change from Baseline to Week 12
GroupValue95% CI
Placebo2.4± 12.21
VAY736 3 mg/kg-23.2± 31.10
VAY736 10 mg/kg-16.5± 18.96
Change in the Patient's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS) Secondary · 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).

Baseline
GroupValue95% CI
Placebo56.2± 24.86
VAY736 3 mg/kg67.2± 13.69
VAY736 10 mg/kg59.8± 24.30
Week 12
GroupValue95% CI
Placebo55.2± 21.57
VAY736 3 mg/kg44.2± 22.75
VAY736 10 mg/kg40.8± 20.49
Change from Baseline to Week 12
GroupValue95% CI
Placebo-1.0± 17.71
VAY736 3 mg/kg-23.0± 25.73
VAY736 10 mg/kg-19.0± 21.08
VAY736 Serum Concentration - AUCinf Secondary · 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.

GroupValue95% CI
VAY736 3 mg/kg389186 – 457
VAY736 10 mg/kg1140515 – 1610
Open Label VAY736971849 – 1340
VAY736 Serum Concentration - AUClast Secondary · 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.

GroupValue95% CI
VAY736 3 mg/kg385184 – 457
VAY736 10 mg/kg1140514 – 1610
Open Label VAY736971848 – 1340
VAY736 Serum Concentration - CL Secondary · 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.

GroupValue95% CI
VAY736 3 mg/kg0.5940.427 – 0.844
VAY736 10 mg/kg0.5840.550 – 1.30
Open Label VAY7360.6860.427 – 0.750
VAY736 Serum Concentration - Cmax Secondary · 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.

GroupValue95% CI
VAY736 3 mg/kg65.045.4 – 76.5
VAY736 10 mg/kg213150 – 283
Open Label VAY736205174 – 217
VAY736 Serum Concentration - T1/2 Secondary · 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.

GroupValue95% CI
VAY736 3 mg/kg8.436.99 – 13.8
VAY736 10 mg/kg9.515.38 – 15.2
Open Label VAY73611.04.94 – 17.4
VAY736 Serum Concentration - Tmax Secondary · 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.

GroupValue95% CI
VAY736 3 mg/kg2.032.00 – 2.20
VAY736 10 mg/kg2.032.00 – 2.30
Open Label VAY7362.102.02 – 2.17

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date subject has provided informed consent until end of study (Week 28 or when B cell recovery was demonstrated, up to 3 years).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 1/9 (11%)
Deaths: 0/9
VAY736 3mg/kg
Serious: 2/6 (33%)
Deaths: 0/6
VAY736 10mg/kg
Serious: 0/12 (0%)
Deaths: 0/12
Open Label VAY736 10mg/kg
Serious: 1/5 (20%)
Deaths: 0/5

Serious adverse events (5 terms)

ReactionSystemPlaceboVAY736 3mg/kgVAY736 10mg/kgOpen Label VAY736 10mg/kg
ColitisGastrointestinal disorders
Inguinal herniaGastrointestinal disorders
AppendicitisInfections and infestations
Jaw fractureInjury, poisoning and procedural complications
Ovarian cyst torsionReproductive system and breast disorders
Other adverse events (42 terms — click to expand)

ReactionSystemPlaceboVAY736 3mg/kgVAY736 10mg/kgOpen Label VAY736 10mg/kg
Infusion related reactionInjury, poisoning and procedural complications
NasopharyngitisInfections and infestations
HeadacheNervous system disorders
Non-cardiac chest painGeneral disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Iron deficiency anaemiaBlood and lymphatic system disorders
PalpitationsCardiac disorders
ChalazionEye disorders
KeratitisEye disorders
Vitreous detachmentEye disorders
Abdominal painGastrointestinal disorders
Auriculotemporal syndromeGastrointestinal disorders
Noninfective sialoadenitisGastrointestinal disorders
ToothacheGastrointestinal disorders
FatigueGeneral disorders
Seasonal allergyImmune system disorders
BronchitisInfections and infestations
ConjunctivitisInfections and infestations
CystitisInfections and infestations
GastroenteritisInfections and infestations
Gastrointestinal infectionInfections and infestations
InfluenzaInfections and infestations
Oral herpesInfections and infestations
Otitis mediaInfections and infestations
SinusitisInfections and infestations
Tooth infectionInfections and infestations
Urogenital infection bacterialInfections and infestations
Ligament ruptureInjury, poisoning and procedural complications
Limb injuryInjury, poisoning and procedural complications
Back painMusculoskeletal and connective tissue disorders
Musculoskeletal painMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
Rotator cuff syndromeMusculoskeletal and connective tissue disorders
Sjogren's syndromeMusculoskeletal and connective tissue disorders
SynovitisMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
InsomniaPsychiatric disorders
Postmenopausal haemorrhageReproductive system and breast disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
Photosensitivity reactionSkin and subcutaneous tissue disorders

Most-reported serious reactions: Colitis, Inguinal hernia, Appendicitis, Jaw fracture, Ovarian cyst torsion.

Data from ClinicalTrials.gov NCT02149420 adverse events section.

Sponsor's own description

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

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Current State of Knowledge on Primary Sjögren's Syndrome, an Autoimmune Exocrinopathy.
    Parisis D, Chivasso C, Perret J, Soyfoo MS, et al · · 2020 · cited 114× · PMID 32698400 · DOI 10.3390/jcm9072299
  2. Combination Therapy for Treating Advanced Drug-Resistant Acute Lymphoblastic Leukemia.
    Vicioso Y, Gram H, Beck R, Asthana A, et al · · 2019 · cited 13× · PMID 31138521 · DOI 10.1158/2326-6066.cir-19-0058
  3. The Future of Targeted Treatment of Primary Sjögren's Syndrome: A Focus on Extra-Glandular Pathology.
    Zeng W, Zhou X, Yu S, Liu R, et al · · 2022 · cited 12× · PMID 36430611 · DOI 10.3390/ijms232214135
  4. Ianalumab (VAY736) in primary Sjögren's syndrome: assessing disease activity using multi-modal ultrasound.
    Diekhoff T, Fischer T, Schefer Q, Posch MG, et al · · 2020 · cited 12× · PMID 33095139
  5. The role of B cell-activating factor system in autoimmune diseases: mechanisms, disease implications, and therapeutic advances.
    Li L, Shen S, Shao S, Dang E, et al · · 2025 · cited 4× · PMID 40547016 · DOI 10.3389/fimmu.2025.1538555
  6. Development and testing of an alternative responder definition for EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI).
    Wratten S, Abetz-Webb L, Arenson E, Griffiths P, et al · · 2023 · cited 2× · PMID 36931685 · DOI 10.1136/rmdopen-2022-002721

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