Sjögren´s Disease
Conditions
Keywords
Sjögren´s disease, ianalumab, VAY736, high symptom burden, B cell depleting therapy, BAFF receptor, BAFF-R, ESSDAI, ESSPRI, SSSD, monoclonal antibody, dryness, fatigue, autoimmune disease, sicca syndrome, THALASSA
Brief summary
The purpose of this study is to demonstrate the efficacy and safety of ianalumab (VAY736) 300 mg administered subcutaneously (s.c.) monthly for 52 weeks in adult participants with Sjögren's disease who have high symptom burden.
Detailed description
This is a double-blind, randomized, placebo-controlled multicenter 2-arm Phase III study, evaluating 300 mg ianalumab s.c. against placebo s.c. in adult participants with Sjögren's disease with high symptom burden.
Interventions
DRUGVAY736
VAY736 once monthly solution for injection for subcutaneous use.
DRUGPlacebo
Placebo once monthly solution for injection for subcutaneous use.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female participants ≥ 18 years of age or as per country-specific legal adult age, whichever is higher * Classification of Sjögren's disease according to ACR/EULAR 2016 criteria. * Seropositive for anti-Ro/SSA antibodies at screening * SSSD oral dryness score ≥ 5 and overall SSSD summary score ≥5 collected over 14 consecutive days during the Screening 2 period * Screening ESSDAI biologic and/or hematologic domain \> 0 Note: laboratory abnormalities for scoring must be confirmed as associated with Sjögren's disease and not be due to other underlying conditions. * Stimulated whole salivary flow (sSF) rate \> 0.3 mL/min at screening * Participants taking hydroxychloroquine (≤ 400 mg/day) are allowed to continue their medication, and must have been on a stable dose for at least 4 weeks prior to screening, which should be maintained throughout the 52 weeks of the blinded treatment period. * Predniso(lo)ne ≤ 5 mg/day or equivalent are allowed for up to 16 weeks post-randomization.
Exclusion criteria
* Presence of another autoimmune rheumatic disease that is active and constitutes the principal illness, specifically: * Systemic sclerosis (SSc) * Any other associated connective tissue disease (e.g., lupus nephritis (LN), large vessel vasculitis (LVV), Sharp syndrome (mixed connective tissue disease)) that is active and requires immunosuppressive treatment outside the scope of this trial and would impede on Sjögren's disease organ domain assessments. * Concurrent diagnosis or history of fibromyalgia or overlapping inflammatory diseases * Prior treatment with B-cell-depleting therapy (e.g., rituximab, other anti-CD20 mAb, anti-CD22 mAb, or anti-CD52 mAb) within: * 36 weeks prior to randomization, or * As long as B-cell count is less than the lower limit of normal (LLN) or baseline value prior to receipt of previous B-cell-depleting therapy (whichever is lower) at Screening. * Prior treatment with ianalumab * Prior treatment with any of the following within the given period prior to Screening: * Within 5 half-lives prior to Screening: iscalimab (anti-CD 40 mAb), belimumab (anti-BAFF mAb), abatacept (CTLA4-Fc Ig), anti-tumor necrosis factor alpha (TNFα) biologic agents, immunoglobulins (i.v./s.c.), plasmapheresis, any other investigational biologic medicines under investigation for Sjögren's disease * Within 4 weeks OR drug-specific 5 half-lives elimination period (if longer than 4 weeks) prior to screening: i.v. or oral cyclophosphamide, mycophenolate mofetil (MMF), methotrexate, azathioprine, i.v. or oral cyclosporine A or any other immunosuppressants (e.g., JAK inhibitors or other kinase inhibitors). * History of hypersensitivity to any of the study drugs or their excipients, or to drugs of similar chemical classes (e.g., mAb of IgG1 class) or to any of the constituents of the study drug formulation (sucrose, L-histidine hydrochloride/L-histidine, polysorbate 20).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in SSSD oral dryness score | Baseline to Week 52 | The Sjögren's Syndrome Symptom Diary (SSSD) oral dryness score is a patient-reported measure assessing severity of mouth dryness. The mouth dryness symptom is scored daily on a numerical scale (higher scores = worse symptoms). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in SSSD summary score | Baseline to Week 52 | The SSSD summary score is calculated over a defined time window. Each symptom is scored daily on a numerical scale (higher scores = worse symptoms). |
| Change from baseline in ESSPRI score | Baseline to Week 52 | The EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) score is a validated patient-reported outcome assessing three symptom domains: dryness, pain and fatigue. Scores range from 0 (no symptoms) to 10 (worst imaginable symptoms). |
| Change from baseline in stimulated whole salivary flow (sSF) | Baseline to Week 52 | The stimulated whole salivary flow rate, is an objective functional assessment of salivary gland activity, measuring saliva production under stimulation. Higher values indicate better salivary gland function. |
| Change from baseline in Patient's Global Assessment (PaGA) NRS score | Baseline to Week 52 | The Patient's Global Assessment of disease activity captures the patient's overall perception of disease activity. It is assessed using a Numerical Rating Scale (NRS) from 0 to 10. Higher scores indicate worse perceived disease activity. |
| Proportion of participants achieving SSSD response | Week 52 | Proportion of participants achieving a clinically meaningful improvement in the SSSD summary score at Week 52. |
| Proportion of participants achieving ESSPRI response | Week 52 | Proportion of participants achieving a clinically meaningful improvement in the ESSPRI score at Week 52. |
| Change from baseline in SSSD eye dryness score | Baseline to Week 52 | The SSSD eye dryness item score is a patient-reported measure assessing severity of eye dryness. The eye dryness symptom is scored daily on a numerical scale (higher scores = worse symptoms). |
| Change from baseline in FACIT-Fatigue score | Baseline to Week 52 | The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score is a 13-item questionnaire assessing fatigue and its impact on daily activities over the previous 7 days. Higher scores indicate less fatigue / better functioning. |
| Change from baseline in Sjögren's-Related Quality of Life (SRQoL) score | Baseline to Week 52 | The Sjögren's-Related Quality of Life (SRQoL) score is a disease-specific quality-of-life instrument evaluating the impact of Sjögren's disease on physical, emotional, social and daily functioning. Lower scores indicate better quality of life. |
Countries
Australia, Canada, South Korea, United States
Contacts
CONTACTNovartis Pharmaceuticals
Outcome results
None listed