Optimizing DMARD-therapy for primary Sjogren's Syndrome - Leflunomide and Hydroxychloroquine combination therapy for patients with primary Sjogren's Syndrome

INTERVENTION: Trade Name: Leflunomide Mylan Product Name: Leflunomide mylan Pharmaceutical Form: Capsule INN or Proposed INN: LEFLUNOMIDE CAS Number: 75706‐12‐6 Concentration unit: Bq/mg becquerel(s)/milligram Concentration type: equal Concentration number: 20‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use Trade Name: Plaquenil Product Name: Plaquenil Pharmaceutical Form: Capsule INN or Proposed INN: HYDROXYCHLOROQUINE CAS Number: 118‐42‐3 Concentration unit: Bq/mg becquerel(s)/milligram Concentration type: equal Concentration number: 400‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use CONDITION: Sjogren's Syndrome ; MedDRA version: 18.0 Level: LLT Classification code 10040766 Term: Sjogren's disease System Organ Class: 10028395 ‐ Musculoskeletal and connective tissue disorders ; MedDRA version: 18.0 Level: PT Classification code 10040767 Term: Sjogren's syndrome System Organ Class: 10028395 ‐ Musculoskeletal and connective tissue disorders ; MedDRA version: 18.0 Level: LLT Classification code 10042846 Term: Syndrome Sjogren's System Organ Class: 10028395 ‐ Musculoskeletal and connective tissue disorders ; MedDRA version: 18.0 Level: LLT Classification code 10040765 Term: Sjogren's System Organ Class: 10028395 ‐ Musculoskeletal and connective tissue disorders Therapeutic area: Diseases [C] ‐ Immune System Diseases [C20] PRIMARY OUTCOME: Main Objective: Reduction in disease activity, measured by ESSDAI (EULAR Sjogren's syndrome disease activity index) Primary end point(s): Improvement of disease activity measured by ESSDAI Secondary Objective: Improvement of dryness measured by stimulated whole saliva output Timepoint(s) of evaluation of this end point: After 24 weeks of treatment with either LEF and HCQ, or placebo‐LEF and placebo‐HCQ SECONDARY OUTCOME: Secondary end point(s): Dryness measured by stimulated whole saliva Timepoint(s) of evaluation of this end point: After 24 weeks of treatment with either LEF and HCQ, or placebo INCLUSION CRITERIA: 1) women, age 18‐75 years 2) pSS diagnosed according to the American‐European Consensus Criteria, revised in 2002 3) lymphocyte focus score (local lymphocytic infiltrates) =1 in sublablial salivary gland specimen. 4) ESSDAI = 5 5) presence of autoantibodies directed to pSS‐related SSA and/or SSB nuclear antigens 6) use of a reliable method of contraception 7) signed written informed consent 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 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10