A clinical study to investigate ianalumab is effective and safe in the treatment of active Sjögren`s syndrome

Phase 1

• Conditions: Active Sjögren’s syndrome; MedDRA version: 21.0Level: PTClassification code 10040767Term: Sjogren's syndromeSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2021-005687-22-DE
• Lead Sponsor: ovartis Pharma AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-04-07
• Last Update Posted: 15 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 489

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

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 less than the lower limit of normal or baseline value prior to receipt of previous B cell-depleting therapy (whichever is lower) 5. Prior treatment with any of the following: -within 24 weeks prior to randomization: iscalimab (anti CD-40 mAb)), belimumab (anti-BAFF mAb), abatacept (CTLA4- Fc Ig), anti-tumor necrosis factor alpha (TNFa) biologic agents, immunoglobulins (i.v./s.c.) plasmapheresis; within 12 weeks prior to randomization: i.v. or oral cyclophosphamide and mycophenolate mofetil (MMF), i.v. or oral cyclosporine A or any other immunosuppressants (e.g., JAK inhibitors or other kinase inhibitors) unless explicitly allowed in inclusion criterion #9
6. Use of corticosteroids (predniso(lo)ne or equivalent corticosteroid) at dose >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 recurrent 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 pos

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified