Three-arm study of the clinical efficacy, safety and tolerability of ianalumab (VAY736) in patients with active Sjögren’s syndrome
- Conditions
- Health Condition 1: M350- Sicca syndrome [Sjogren]
- Registration Number
- CTRI/2023/02/049813
- Lead Sponsor
- ovartis Healthcare Pvt Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- Not specified
- Target Recruitment
- 0
1-Signed informed consent must be obtained prior to participation in the study
2-Women and men greater than or equal to 18 years of age
3-Classification of Sjogrens syndrome according to the ACR/EULAR 2016 criteria (Shiboski et al 2017)
4-Time since diagnosis of Sjogrens of less than or equal to 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 less than or equal to 10 percent of the study population
5-Screening ESSDAI score of greater than or equal to 5 within the following 8 domains: constitutional, lymphadenopathy, glandular, articular, cutaneous, renal, hematological and biologic.
6-Stimulated whole salivary flow (sSF) rate of greater than or equal to 0.05 mL/min at screening
7-Ability to communicate well with the Investigator, understand and agree to comply with the requirements of the study
Patients taking hydroxychloroquine (less than or equal to 400 mg/day), methotrexate (less than or equal to 25 mg/week) or azathioprine (less than or equal to 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
8-Patients taking systemic corticosteroids have to be on a stable dose of less than or equal to 10 mg per 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
9-Patients taking-
--disease-modifying antirheumatic drugs (DMARDs) other than specifically allowed in inclusion criterion number 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.
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 Sjogrens 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 less than 50 cells per microliter
5-Prior treatment with any of the following within 6 months prior to randomization-
--iscalimab (anti CD-40), belimumab (anti-BAFF mAb), abatacept (CTLA4-Fc Ig), anti-tumor necrosis factor alpha (TNFa) biologic agents, immunoglobulins (i.v. (intravenous)/s.c.) plasmapheresis; i.v. or oral cyclophosphamide and mycophenolate mofetil (MMF), i.v. or oral cyclosporine A
--any other immunosuppressants (e.g., JAK inhibitors or other kinase inhibitors) unless explicitly allowed in inclusion criterion number 9
7-Use of corticosteroids (predniso(lo)ne or equivalent corticosteroid) at dose greater than 10 mg/day
8-Any one of the following laboratory values at screening-
--Hemoglobin levels less than 8.0 g/dL
--White blood cells (WBC) count less than 2.0 x 103/microliter
--Platelet count less than 80 x 103/microliter
--Absolute neutrophil count (ANC) less than 0.8 x 103/microliter (one re-test is allowed during the screening period)
9- 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.
10-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 (sucrose, L-histidine hydrochloride/ L-histidine, polysorbate 20).
11-History of major organ, hematopoietic stem cell or bone marrow transplant.
Required regular use of medications known to cause dry mouth/eyes as 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. <
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Change from baseline in ESSDAI score; to demonstrate superiority of ianalumab over placebo based on this changeTimepoint: At Week 48
- Secondary Outcome Measures
Name Time Method Demonstration of superiority of ianalumab over placebo based on proportion of patients achieving greater than or equal to 3 points reduction from baseline in ESSDAI scoreTimepoint: At week 24;Demonstration of superiority of ianalumab over placebo based on proportion of patients- <br/ ><br>-achieving greater than or equal to 3 points reduction from baseline in ESSDAI score <br/ ><br>-achieving low systemic disease activity defined as ESSDAI less than 5 <br/ ><br>-achieving greater than or equal to 1 point or 15 percent reduction from baseline in ESSPRITimepoint: At week 48;Demonstration of superiority of ianalumab over placebo based on- <br/ ><br>-change from baseline in stimulated whole salivary flow (sSF) rate <br/ ><br>-change from baseline in Physician’s Global Assessment (PhGA) <br/ ><br>-change from baseline in Patient’s Global Assessment (PaGA) <br/ ><br>-change from baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scoreTimepoint: At week 48