NCT05113004

New Clinical End-points in Patients With Primary Sjögren's Syndrome

NEw Clinical Endpoints in Patients With Primary Sjögren's Syndrome (pSS): an Interventional Trial Based on stratifYing Patients

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 300 (estimated)
• Sponsor: Assistance Publique - Hôpitaux de Paris · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Primary Sjögren's Syndrome (pSS)

Interventions

Type	Name	Description
DRUG	Hydroxychloroquine 400mg/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.
DRUG	Leflunomide 20mg/d	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.
DRUG	Mycophenolate mofetil 2000mg/d	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).
DRUG	Placebo of Hydroxychloroquine 400mg/d	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.
DRUG	Placebo of Leflunomide 20mg/d	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
DRUG	Placebo of Mycophenolate mofetil 2000mg/d	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).

Timeline

• Start date: 2022-01-20
• Primary completion: 2025-04-01
• Completion: 2025-10-01
• First posted: 2021-11-09
• Last updated: 2024-11-01

Locations

7 sites across 1 country: France