Active Sjögren’s syndrome MedDRA version: 21.0 Level: PT Classification code 10040767 Term: Sjogren's syndrome System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants eligible for this study must meet all the following criteria: 1. Signed informed consent must be obtained prior to participation in the study 2. Women and men = 18 years of age 3. Classification of Sjögren's syndrome according to the ACR/EULAR 2016 criteria (Shiboski et al 2017) 4. Time since diagnosis of Sjögren's of = 7.5 years at screening 5. Positive anti-Ro/SSA antibody at screening ? Patients negative for anti-Ro/SSA antibody are eligible, if they have a positive salivary gland biopsy confirmed by central expert review ? Enrollment of anti-Ro/SSA-negative patients will be limited up to =10% of the study population 6. Screening ESSDAI score of = 5 within the following 8 domains: constitutional, lymphadenopathy, glandular, articular, cutaneous, renal, hematological and biologic. 7. Stimulated whole salivary flow (sSF) rate of = 0.05 mL/min at screening 8. Ability to communicate well with the Investigator, understand and agree to comply with the requirements of the study 9. Patients taking hydroxychloroquine (= 400 mg/day), methotrexate (= 25 mg/week) or azathioprine (= 150 mg/day) alone or in combination are allowed to continue their medication and must have been on a stable dose for at least 30 days prior to randomization. Stable dose within the predefined dose limits should be maintained throughout the 52 weeks of the blinded treatment period of the study 10. Patients taking systemic corticosteroids have to be on a stable dose of = 10 mg/day predniso(lo)ne or equivalent for at least 30 days before randomization. Stable dose should be maintained throughout the 52 weeks of the blinded treatment period of the study, however limited increases of the corticosteroid dose for a limited time and tapering of background steroids are allowed during the course of the study as described in Section 6.2.1 11. Patients taking ? disease-modifying antirheumatic drugs (DMARDs) other than specifically allowed in inclusion criterion #9, or ? the following Traditional Chinese Medicines: Total glucoside of peony (TGP) or Tripterium glycosides (TG) must discontinue these medications at least 30 days prior to randomization, except for leflunomide, which has to be discontinued for 8 weeks prior to randomization unless a cholestyramine wash-out has been performed. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 420 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 69
Exclusion criteria
Exclusion criteria: Exclusion criteria 1. Presence of another autoimmune rheumatic disease that is active and constitutes the principal illness, specifically: - Moderate-to-severe active systemic lupus erythematosus (SLE) with anti-dsDNA positivity and renal involvement, or other organ involvement that impedes on ability to score ESSDAI domains - Active rheumatoid arthritis (RA) that impedes on the ability to score the ESSDAI articular domain - Systemic sclerosis - Any other concurrent 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 syndrome organ domain assessments. 2. Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days or until the expected pharmacodynamic effect has returned to baseline, whichever is longer, or longer if required by local regulations 3. Prior treatment with ianalumab 4. Prior use of a B-cell depleting therapy other than ianalumab (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 10 mg/day 7. Any one of the following laboratory values at screening: - Hemoglobin levels < 8.0 g/dL - White blood cells (WBC) count < 2.0 x 103/µL - Platelet count < 80 x 103/µL - Absolute neutrophil count (ANC) < 0.8 x 103/µL (one re-test is allowed during the screening period) 8. Active viral, bacterial or other infections requiring systemic treatment at the time of screening or randomization, or history of recurrent clinically significant infection or of bacterial infections with encapsulated organisms 9. History of hypersensitivity to any of the study drugs or its 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, Lhistidine hydrochloride/ L-histidine, polysorbate 20) 10. History of major organ, hematopoietic stem cell or bone marrow transplant 11. Required regular use of medications known to cause dry mouth/eyes as a regular and major side effect, and which have not been on a stable dose for at least 30 days prior to Screening, or any anticipated change in the treatment regimen during the course of the study 12. Use of topical ocular prescription medications (excluding artificial tears, gels, lubricants) that have not been on a stable dose for at least 90 days prior to randomization, or any anticipated change in the treatment regimen during the course of the study 13. Receipt of live/attenuated vaccine within a 4-week period prior to randomization 14. History of primary or secondary immunodeficiency, including a positive human immunodeficiency virus (HIV) (ELISA and Western blot) test result 15. History of malignancy of any organ system (other than localized basal cel
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate superiority of ianalumab over placebo based on change from baseline in ESSDAI score at Week 48. ;Secondary Objective: Key secondary objectives Plan B (EU): To demonstrate superiority of ianalumab over placebo based on: ? proportion of patients achieving =3 points reduction from baseline in ESSDAI score at Week 48 ? proportion of patients achieving low systemic disease activity defined as ESSDAI<5 at Week 48 ? To evaluate the proportion of patients achieving = 1 point or 15% reduction from baseline in ESSPRI at Week 48 To demonstrate superiority of ianalumab over placebo based on: ? proportion of patients achieving =3 points reduction from baseline in ESSDAI score at Week 24 ? change from baseline in stimulated whole salivary flow (sSF) rate at Week 48 ? change from baseline in Physician’s Global Assessment (PhGA) at Week 48 ? change from baseline in Patient's Global Assessment (PaGA) at Week 48 ? change from baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score at Week 48 ;Primary end point(s): Change from baseline in ESSDAI score as compared to placebo;Timepoint(s) of evaluation of this end point: Week 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary end points Plan B (EU): ? Proportion of patients achieving = 3 points reduction from baseline in ESSDAI score at Week 48 ? Proportion of patients achieving ESSDAI < 5 at Week 48 ? Proportion of patients achieving = 1 point or 15% reduction from baseline in ESSPRI at Week 48 ? Proportion of patients achieving = 3 points reduction from baseline in ESSDAI score at Week 24 ? Change from baseline in stimulated whole salivary flow rate at Week 48 ? Change from baseline in PhGA at Week 48 ? Change from baseline in PaGA at Week 48 ? Change from baseline in FACIT-F score at Week 48 ;Timepoint(s) of evaluation of this end point: Week 48 or week 24 respectively, see section E.5.2 | — |
Countries
Argentina, Australia, Brazil, Bulgaria, Canada, Chile, China, Colombia, France, Germany, Greece, Hungary, Iceland, India, Israel, Italy, Japan, Lebanon, Mexico, Peru, Poland, Romania, Slovakia, South Africa, Spain, Sweden, Taiwan, United Kingdom, United States
Contacts
Public ContactInformation&Communication Médicales
Novartis Pharma S.A.S
Outcome results
None listed