A Phase 2 interventional study of Hydroxychloroquine 400mg/d and Leflunomide 20mg/d in Primary Sjögren's Syndrome (pSS), sponsored by Assistance Publique - Hôpitaux de Paris. Recruiting at 7 sites in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-11-01.
Sponsored by Assistance Publique - Hôpitaux de Paris · Phase 2, Interventional, and Treatment
There are no approved treatments for pSS and the clinical endpoints currently used in clinical trials are inadequate to capture all aspects of the disease that should be evaluated in clinical trials. The newly developed composite endpoint: Sjögren's Tool for Assessing Response to treatment (STAR) will allow a more specific and meaningful assessment of treatment efficacy in pSS.
Because of the heterogeneity of the disease and of the central role of the interplay between B- and T-cells in the pathogenesis, it is worth to evaluate combination of conventional synthetic immunomodulatory drugs targeting both B- and T-cells.
Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease with a female-to-male predominance of 9:1 and a peak incidence at 50 years of age. It is characterized by chronic inflammation and subsequent destruction of exocrine glands, mainly lacrimal and salivary glands, with ocular and oral dryness. Patients also experience joint pain and extreme fatigue. In 20-40% of patients, the inflammatory process extends beyond the exocrine glands and patients experience systemic extra glandular manifestations, with 5-10% developing B-cell lymphoma.
Two populations of pSS patients can be defined. Patients with dryness, fatigue, pain and low systemic activity present no or limited long-term extraglandular damage but they have a profoundly reduced quality of life with marked anxiety, depression, and social isolation (Rischmueller 2016)(Meijer, 2009). Patients with high systemic activity have important long-term damage and bad prognosis. To date, there are no approved disease-modifying treatments.
Current clinical outcome assessment (COA) tools in pSS have shown important weaknesses (e.g. high placebo response rate) which may hamper demonstration of therapeutic benefit. A novel COA called STAR has recently been developed by the NECESSITY consortium (funded by the Innovative Medicines Initiative) and should allow the identification of new therapeutic options for both patient populations.
the investigator aim to demonstrate, thanks to the new STAR outcome measure, efficacy of a combination therapy targeting both B- and T-cells in pSS patients.
371 studies on the registry are indexed under Sjogren's Syndrome; 104 are open to participants now.
This study's planned enrollment of 300 is above the median of 50 across 244 interventional studies indexed under Sjogren's Syndrome.
Browse Sjogren's Syndrome studies →Assistance Publique - Hôpitaux de Paris is the lead sponsor of 3,505 studies on the registry; 1,006 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Cohort 1 : Patients with High levels of symptoms and low disease activity receive : Placebo of Leflunomide 20mg/d Placebo of Mycophenolate mofetil 2000mg/d Placebo of hydroxychloroquine 400mg/d
Drug: Placebo of Hydroxychloroquine 400mg/d · Drug: Placebo of Leflunomide 20mg/d · Drug: Placebo of Mycophenolate mofetil 2000mg/d
Cohort 1 : Patients with High levels of symptoms and low disease activity receive : Leflunomide 20mg/d hydroxychloroquine 400mg/d Placebo of Mycophenolate mofetil 2000 mg/d
Drug: Hydroxychloroquine 400mg/d · Drug: Leflunomide 20mg/d · Drug: Placebo of Mycophenolate mofetil 2000mg/d
Cohort 1 : Patients with High levels of symptoms and low disease activity receive : Placebo of Leflunomide 20mg/d Mycophenolate mofetil 2000mg/d hydroxychloroquine 400mg/d
Drug: Hydroxychloroquine 400mg/d · Drug: Mycophenolate mofetil 2000mg/d · Drug: Placebo of Leflunomide 20mg/d
Cohorte 2 :Patients with moderate or hight activity, regardless of level of symptoms, they receive : Placebo of Leflunomide 20mg/d Placebo of Mycophenolate mofetil 2000mg/d Placebo of hydroxychloroquine 400mg/d
Drug: Placebo of Hydroxychloroquine 400mg/d · Drug: Placebo of Leflunomide 20mg/d · Drug: Placebo of Mycophenolate mofetil 2000mg/d
Cohorte 2 :Patients with moderate or hight activity, regardless of level of symptoms, they receive : Leflunomide 20mg/d hydroxychloroquine 400mg/d Placebo of Mycophenolate mofetil 2000 mg/d
Drug: Hydroxychloroquine 400mg/d · Drug: Leflunomide 20mg/d · Drug: Placebo of Mycophenolate mofetil 2000mg/d
Cohorte 2 :Patients with moderate or hight activity, regardless of level of symptoms, they receive : Placebo of Leflunomide 20mg/d Mycophenolate mofetil 2000mg/d hydroxychloroquine 400mg/d
Drug: Hydroxychloroquine 400mg/d · Drug: Leflunomide 20mg/d · Drug: Placebo of Leflunomide 20mg/d
Hydroxychloroquine (HCQ) is a 4-aminoquinoline belonging to the group of antimalarial agents. Its immunomodulatory activity on B-cells has mainly been attributed to its inhibition of antigen presentation, cytokine production, and recently on Toll-like receptor signaling and IFN secretion that drives B cell activation.
Leflunomide (LEF) is a derivative of isoxazole and is converted into an active metabolite which blocks de novo synthesis of pyrimidines in activated T lymphocytes, thereby inhibiting T cell proliferation and consequently T cell-dependent B cell formation of autoantibodies.
Mycophenolate mofetil (MMF) is a morpholinoethyl ester of mycophenolic acid which blocks proliferation of lymphocytes by inhibiting the de novo pathway of purine biosynthesis (Allison, 2000).
Placebo of Hydroxychloroquine (HCQ) is a 4-aminoquinoline belonging to the group of antimalarial agents. Its immunomodulatory activity on B-cells has mainly been attributed to its inhibition of antigen presentation, cytokine production, and recently on Toll-like receptor signaling and IFN secretion that drives B cell activation.
Placebo of Leflunomide (LEF) is a derivative of isoxazole and is converted into an active metabolite which blocks de novo synthesis of pyrimidines in activated T lymphocytes, thereby inhibiting T cell proliferation
Placebo of Mycophenolate mofetil (MMF) is a morpholinoethyl ester of mycophenolic acid which blocks proliferation of lymphocytes by inhibiting the de novo pathway of purine biosynthesis (Allison, 2000).
Cohort 1. Proportion of patients achieving a response according to preliminary STAR at week 24 between each active treatment arm and placebo arm.
Time frame: During the 24 weeks of the trials
Cohort 2. Proportion of patients achieving a response according to preliminary STAR at week 24 between each active treatment arm and placebo arm.
Time frame: During the 24 weeks of the trials
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