E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Active Sjögren's syndrome |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10040767 |
E.1.2 | Term | Sjogren's syndrome |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate superiority of ianalumab over placebo based on change from baseline in ESSDAI score at Week 48
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E.2.2 | Secondary objectives of the trial |
Key secondary objectives analysis 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.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Participants eligible for inclusion in this study must meet all of 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 must or ● the following Traditional Chinese Medicines: Total glucoside of peony (TGP) 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. |
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E.4 | Principal 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 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 (TNFα) biologic agents, immunoglobulins (i.v./s.c.) plasmapheresis; - within 12 weeks prior to randomization: i.v. or oral cyclophosphamide, 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 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, L-histidine 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 cell carcinoma of the skin or in situ cervical cancer or Sjögren’s related lymphoma), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. 16. History of sarcoidosis 17. Any surgical, medical (e.g., uncontrolled hypertension, heart failure or diabetes mellitus), psychiatric or additional physical condition that the Investigator feels may jeopardize the patient in case of participation in this study 18. Chronic infection with hepatitis B (HBV) or hepatitis C (HCV). 19. Evidence of active tuberculosis (TB) infection is exclusionary. Patients with previously treated TB and previously treated or newly diagnosed latent TB may be eligible (after anti-TB treatment, patients with history of or latent TB may become eligible according to national guidelines) 20. Pregnant or nursing (lactating) women 21. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while on study treatment and for 6 months after stopping of investigational medication. 22. Patients with a known history of non-compliance to medication, or who were unable or unwilling to complete PRO questionnaires, or who are unable or unwilling to use the device for collection of PROs. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in ESSDAI score as compared to placebo
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary endpoints 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
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
48 or 24 weeks respectively (detail see section E.5.2) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
tolerability, immunogenicity |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 39 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Chile |
Guatemala |
Singapore |
Korea, Democratic People's Republic of |
Brazil |
China |
Mexico |
United States |
Austria |
Belgium |
Czechia |
France |
Germany |
Lithuania |
Poland |
Portugal |
Spain |
Türkiye |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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LVLS (referred to in the protocol LPLV= Last Patient Last Visit) |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 14 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 9 |