A Phase II Study With Low-dose Recombinant Human IL-2 for the Treatment of Primary Sjögren's Syndrome

A Phase II Study With Low-dose Recombinant Human IL-2 for the Treatment of Primary Sjögren's Syndrome

Primary Sjögren's Syndrome (pSS) is an autoimmune disorder characterized by keratoconjunctivitis sicca and xerostomia. In addition, various extraglandular manifestations may develop. Several immunomodulating agents have been attempted in the treatment of pSS without achieving satisfactory results. Currently, there is no approved systemic treatment for pSS. Dysfunction of regulatory T (Treg) cells has been detected in diverse autoimmune diseases, which can be promoted by interleukin-2 (IL-2). The investigators hypothesized that low-dose IL-2 could be a novel therapy in active pSS patients. This clinical study will test the efficacy and safety of low dose IL-2 treatment in pSS. The investigators perform a single-centre, double-blind pilot trial with hrIL-2 in pSS. The investigators evaluate the effectiveness and safeness of low-dose hrIL-2 for primary Sjögren's Syndrome by randomized controlled study (hrIL-2 (N = 30) versus placebo group (N = 30)).

Each pSS patients (n=60) with Scores>=6 on ESSDAI received low-dose IL-2 or placebo (active group: placebo group =1:1, 1 million units every other day subcutaneously (HrIL-2 1X 106, ip, Qod) for a period of 14 days. After a 14-day rest, another cycle started) for 3 cycles. The end points were safety, clinical and immunologic response.

Intervention：Add hrIL-2 according to the protocol to original treatment. HrIL-2 active: 1 million U doses of human recombinant interleukin-2 s.c. injection

Examination of the therapeutic effects (improvement in ESSDAI) of low dose IL-2 in patients with primary Sjögren's Syndrome

Analysis regulatory CD4+ T (Treg) cells , interleukin 17 (IL-17)-producing helper T (Th17) cells and follicular helper T (Tfh) cells before and during IL-2 treatment. P values below 0.05 are considered statistically significant in this study

Inclusion Criteria: Diagnosis of a primary Sjögren´s Syndrome ESSDAI score ≥ 6 Liver values above 1,5 ULN Stable low dose systemic use of Glucocorticoids（<=7.5mg） in the last 4 weeks before begin with Study medication Exclusion Criteria: Secondary Sjögren's Syndrome Pre-treatment with Cyclosporine A Receiving cyclosphosphamide, corticosteroid bolus with dose over 1 mg/kg, rituximab, belimumab, other immunosuppressives Infection Neoplasia Relevant cardiac, pulmonary, neurologic or psychiatric disease Life-Vaccination within 4 weeks before begin with study medication Pregnant or breast-feeding Weight under 45kg or more than 80kg

He J, Chen J, Miao M, Zhang R, Cheng G, Wang Y, Feng R, Huang B, Luan H, Jia Y, Jin Y, Zhang X, Shao M, Wang Y, Zhang X, Li J, Zhao X, Wang H, Liu T, Xiao X, Zhang X, Su Y, Mu R, Ye H, Li R, Liu X, Liu Y, Li C, Liu H, Hu F, Guo J, Liu W, Zhang WB, Jacob A, Ambrus JL Jr, Ding C, Yu D, Sun X, Li Z. Efficacy and Safety of Low-Dose Interleukin 2 for Primary Sjogren Syndrome: A Randomized Clinical Trial. JAMA Netw Open. 2022 Nov 1;5(11):e2241451. doi: 10.1001/jamanetworkopen.2022.41451.