Safety and Efficacy of VAY736 in Patients With Primary Sjogren's Syndrome (pSS)

Study of Safety and Efficacy of Multiple VAY736 Doses in Patients With Moderate to Severe Primary Sjogren's Syndrome (pSS)

The purpose of this study was to determine the dose-response relationship of VAY736 for key efficacy and safety parameters

Study Overview

• Status: Completed
• Conditions: Primary Sjogren Syndrome
• Intervention / Treatment: Other: Placebo; Biological: VAY736

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.

• Study Type: Interventional
• Enrollment (Actual): 190
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Caba, Argentina, 1117
    • Novartis Investigative Site
  • Cordoba, Argentina, X5016KEH
    • Novartis Investigative Site
  • Cordoba, Argentina, 5000
    • Novartis Investigative Site
  • Buenos Aires
    • Ciudad Autonoma de Bs As, Buenos Aires, Argentina, C1055AAF
      • Novartis Investigative Site
• Austria
  • Graz, Austria, 8036
    • Novartis Investigative Site
• Belgium
  • Bruxelles, Belgium, 1070
    • Novartis Investigative Site
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
• Chile
  • Santiago, Chile, 7500710
    • Novartis Investigative Site
  • Santiago, Chile, 8207257
    • Novartis Investigative Site
• France
  • Brest, France, 29200
    • Novartis Investigative Site
  • Lille, France, 59037
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 13353
    • Novartis Investigative Site
  • Freiburg, Germany, 79106
    • Novartis Investigative Site
  • Muenchen, Germany, 81377
    • Novartis Investigative Site
  • Wuerzburg, Germany, 97080
    • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, H-1097
    • Novartis Investigative Site
  • Szeged, Hungary, 6720
    • Novartis Investigative Site
• Israel
  • Ramat Gan, Israel, 52621
    • Novartis Investigative Site
• Italy
  • MI
    • Rozzano, MI, Italy, 20089
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00161
      • Novartis Investigative Site
  • UD
    • Udine, UD, Italy, 33100
      • Novartis Investigative Site
• Japan
  • Aichi
    • Nagoya, Aichi, Japan, 457 8510
      • Novartis Investigative Site
  • Nagasaki
    • Sasebo-city, Nagasaki, Japan, 857-1165
      • Novartis Investigative Site
  • Tokyo
    • Itabashi-ku, Tokyo, Japan, 173-8610
      • Novartis Investigative Site
    • Shinjuku-ku, Tokyo, Japan, 160 8582
      • Novartis Investigative Site
• Netherlands
  • Zuid Holland
    • Rotterdam, Zuid Holland, Netherlands, 3015 GD
      • Novartis Investigative Site
• Poland
  • Lublin, Poland, 20-954
    • Novartis Investigative Site
• Portugal
  • Almada, Portugal, 2801 951
    • Novartis Investigative Site
  • Lisboa, Portugal, 1050-034
    • Novartis Investigative Site
  • Lisboa, Portugal, 1649 035
    • Novartis Investigative Site
  • Porto, Portugal, 4099-001
    • Novartis Investigative Site
• Romania
  • Brasov, Romania, 500283
    • Novartis Investigative Site
  • Cluj Napoca, Romania, 400006
    • Novartis Investigative Site
• Russian Federation
  • Ekaterinburg, Russian Federation, 620028
    • Novartis Investigative Site
  • Moscow, Russian Federation, 115522
    • Novartis Investigative Site
  • Orenburg, Russian Federation, 460000
    • Novartis Investigative Site
  • St Petersburg, Russian Federation, 195257
    • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08041
    • Novartis Investigative Site
  • Pontevedra
    • Vigo, Pontevedra, Spain, 36200
      • Novartis Investigative Site
  • Santa Cruz De Tenerife
    • La Laguna, Santa Cruz De Tenerife, Spain, 38320
      • Novartis Investigative Site
• Taiwan
  • Kaohsiung, Taiwan, 81346
    • Novartis Investigative Site
  • Taichung, Taiwan, 40447
    • Novartis Investigative Site
  • Taichung, Taiwan, 407219
    • Novartis Investigative Site
  • Taipei, Taiwan, 11490
    • Novartis Investigative Site
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Novartis Investigative Site
  • Liverpool, United Kingdom, L9 7AL
    • Novartis Investigative Site
  • Southend, United Kingdom, SSO 0RY
    • Novartis Investigative Site
• United States
  • Florida
    • Plantation, Florida, United States, 33324
      • Integral Rheumatology and Immunology Specialists IRIS
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana Univ School of Dentistry
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • The John Hopkins Jerome L Greene Sjogren
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts School of Dental Medicine
  • New York
    • Rochester, New York, United States, 14618
      • AAIR Research Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC
    • Wexford, Pennsylvania, United States, 15090
      • Advanced Rheumatology and Arthritis Wellness Center
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • San Antonio, Texas, United States, 78229
      • First Outpatient Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo control	Other: Placebo; Placebo control
Experimental: VAY736 dose 1 - 5mg; VAY736 low	Biological: VAY736; VAY736; Other Names: Ianalumab
Experimental: VAY736 dose 2 - 50mg; VAY736 medium	Biological: VAY736; VAY736; Other Names: Ianalumab
Experimental: VAY736 dose 3 - 300 mg; VAY736 high	Biological: VAY736; VAY736; Other Names: Ianalumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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 Outcome Measures

Outcome Measure	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.	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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 27, 2017
• Primary Completion (Actual): June 30, 2020
• Study Completion (Actual): September 23, 2021

Study Registration Dates

• First Submitted: November 3, 2016
• First Submitted That Met QC Criteria: November 9, 2016
• First Posted (Estimated): November 15, 2016

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 6, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: VAY736; Sjogren; ianalumab; pSS
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Mouth Diseases; Stomatognathic Diseases; Pathologic Processes; Arthritis; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Disease; Eye Diseases; Arthritis, Rheumatoid; Xerostomia; Salivary Gland Diseases; Dry Eye Syndromes; Lacrimal Apparatus Diseases; Syndrome; Sjogren's Syndrome
• Other Study ID Numbers: CVAY736A2201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan 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.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No