A Study to Evaluate the Efficacy and Safety of Iguratimod Compared to Placebo in Patients With Active Primary Sjogren's Syndrome.

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of iguratimod compared to placebo in patients with active primary Sjogren's Syndrome.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Multicenter Phase II Clinical Study to Evaluate the Efficacy and Safety of Iguratimod in Patients With Active Primary Sjogren's Syndrome.

Conditions
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Primary Sjögren Syndrome

Intervention / Treatment
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* Drug: Iguratimod
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: meet the 2016 American College of Rheumatology (ACR) / European League Against Rheumatism Classification Criteria for Sjogren's Syndrome (EULAR SS) ESSDAI score ≥6 IgG >16 g/L Positive anti-SS-A/Ro antibody at screening Exclusion Criteria: Pregnancy or breast feeding Secondary Sjogren's syndrome severe renal or haematological failure, a history of cancer, hepatitis B or C, human immunodeficiency virus, severe diabetes or any other chronic disease or evidence of infection Prior administration of any of the following: Rituximab in the past 12 months prior to randomization; Cyclophosphamide, mycophenolate mofetil, methotrexate, leflunomide and iguratimod in the past 12 weeks prior to randomization; Azathioprine, cyclosporin, tacrolimus, sirolimus, sulfasalazine in the past 4 weeks prior to randomization; live vaccine in the past 12 weeks prior to randomization Corticosteroids: > 10 mg/day oral prednisone (or equivalent); Any change or initiation of new dose within 4 weeks prior to randomization; Intramuscular, subcutaneous, intravenous, or intra-articular corticosteroids within 4 weeks prior to randomization.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Iguratimod 1<br>orally 25mg twice a day | Drug: Iguratimod<br>* Iguratimod orally twice a day<br>|
| Experimental: Iguratimod 2<br>orally 20mg twice a day | Drug: Iguratimod<br>* Iguratimod orally twice a day<br>|
| Experimental: Iguratimod 3<br>orally 10mg twice a day | Drug: Iguratimod<br>* Iguratimod orally twice a day<br>|
| Placebo Comparator: Placebo<br>orally twice a day | Drug: Placebo<br>* Placebo orally twice a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI) | The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) total score is calculated as the sum of scores for activity level for each domain. Overall score, which can range from 0 to 123, a higher score indicates more disease activity | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI) | The total score EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) is calculated as the mean of the 3 individual components. Total Score Range (0 = Best outcome and 10 = Worst Outcome) The scores for the ESSPRI individual components will be used as such reported by the participants and entered in the case report form (CRF), without any further calculations. It consists of 3 questions covering cardinal symptoms of Sjögren's syndrome: dryness, fatigue and pain. Each domain scored on scale of 0-10 (0 =no symptom at all and 10 = worst symptom imaginable), and overall score is calculated as the mean of 3 individual domains. | Week 12 | 
| Change From Baseline in the Unstimulated Salivary Flow | The mean change from baseline in unstimulated whole salivary flow at all measured time points up to Week 12 | Week 12 | 
| Change From Baseline in Schirmer's Test | The Mean change from baseline in Schirmer's Test at all measured time points up to Week 12 The length in millimeters that the strip wets during the 5 minute test period for each eye. Collection is done separately for each eye. | Week 12 | 
| Change From Baseline in the level of immunoglobulin (IgG, IgA, IgM) | The change from baseline in the level of immunoglobulin (IgG, IgA, IgM) at all measured time points up to Week 12 | Week 12 | 
| Change From Baseline in the level of rheumatoid factor (RF) | The change from baseline in the level of RF at all measured time points up to Week 12 | Week 12 | 
| Change From Baseline in the level of B -cell activation factor (BAFF) | The change from baseline in the level of BAFF at all measured time points up to Week 12 | Week 12 | 
| Change From Baseline in the level of T/B/NK cell subsets | The change from baseline in the level of T/B/NK cell subsets at all measured time points up to Week 12 | Week 12 | 
| Change From Baseline in the level of erythrocyte sedimentation rate (ESR) | The change from baseline in the level of ESR at all measured time points up to Week 12 | Week 12 | 
| Change From Baseline in the level of serum complement (C3 and C4) | The change from baseline in the level of serum complement (C3 and C4) at all measured time points up to Week 12 | Week 12 |