New Clinical End-points in patients with primary Sjögren’s Syndrome: an Interventional Trial based on stratifYing patients

Prior treatment

• Previous treatment with HCQ, LEF, or MMF in the last 3 months
• Previous treatment with rituximab, other B-cell targeted biologic therapy or cyclophosphamide in the last 6 months
• Previous treatment with anti-TNF, abatacept, tocilizumab or belimumab or any other biologic in the setting of a past clinical trial in the last 3 months
• Severe life-threatening systemic involvement requiring cyclophosphamide or high-dose corticosteroids, or any drug considered as an exclusion criteria
• Concomitant treatment with corticosteroids more than 10 mg/day of prednisone equivalent at screening or inclusion (randomisation)
• Concomitant treatment with other immunomodulators including methotrexate, azathioprine, cyclophosphamide, cyclosporine and tacrolimus

Other illness

• Impairment of other severe immunodeficiency states
• Patients with active malignancy or history of malignancy within the last 5 years except non-melanoma skin cancer
• Patients with active gastrointestinal tract ulceration, hemorrhage and perforation
• Patients with history of cardiomyopathy
• Patients with known hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) such as Lesch-Nyhan and Kelley-Seegmiller syndrome
• Serious infection in the past month
• Evidence of active tuberculosis infection
• Active HCV (positive PCR)
• Active HBV infection (positivity for HBS antigen, or positivity for anti-HBC antibody without any HBS antigen)
• HIV infection (positive serology)
• Positive SARS-Cov2 PCR (if vaccinated for COVID-19, no PCR is required; if history of COVID-19 infection, positive serology is sufficient)
• Known history of maculopathy
• Contra-indication to HCQ: pre-existing retinopathy, hypersensitivity to HCQ or to any of the excipients of the specialty used
• Contra-indication tor LEF: hypersensitivity to the active substance, the main active metabolite teriflunomide or to any excipients of the specialty used

Lab values

• Cytopenia defined as neutrophils < 1.0 G/L, lymphocytes < 0.5 G/L, Hb < 10 g/dl or platelets < 100 G/L
• Moderate to severe renal insufficiency (GFR < 30 ml/min)
• Severe hypogammaglobulinemia defined as gamma globulins or IgG < 5 g/l
• Reduced hepatic function: AST or ALT > 2x ULN
• Prolonged ECG's corrected QT interval (>500 ms)
• Contra-indication to MMF: hypersensitivity to mycophenolate mofetil, acid mycophenolic, mycophenolate sodium or to any of the excipients of the specialty used

Age

• Age < 18 years

Other

• Pregnant or breastfeeding women or women wanting to conceive either during or within two years after the end of the treatment period
• Women of childbearing potential not using highly effective methods of contraception
• Patients not informed of the risk of alcohol consumption and of the recommendations to avoid alcohol during the entire study
• Not affiliated to a social security regime (specific for France)
• Participation in another interventional trial

• Cohort 1 : Having given written informed consent prior to undertaking any study-related procedures
• Cohort 2 : Use highly reliable contraception during study treatment from the screening and for two years after stopping treatment
• Cohort 1 : Patients with pSS according to ACR/EULAR 2016 criteria or AECG 2002 criteria
• Cohort 1 : With a high level of symptoms (ESSPRI ≥ 5) and low systemic disease activity
• Cohort 1 : Negative pregnancy test (serum at screening)
• Cohort 1 : Use highly reliable contraception during study treatment from the screening and for two years after stopping treatment
• Cohort 2 : Having given written informed consent prior to undertaking any study-related procedures
• Cohort 2 : Patients with pSS according to ACR/EULAR 2016 criteria or AECG 2002 criteria
• Cohort 2 : With moderate/high systemic disease activity, as defined by ESSDAI ≥ 5
• Cohort 2 : Negative pregnancy test (serum at screening)