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

Study Overview
=================
Brief Summary
-----------------
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)).

Detailed Description
-----------------
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.

Official Title
-----------------
Safety and Efficiency Study of Low-dose IL-2 Treatment in Primary Sjögren's Syndrome

Conditions
-----------------
Primary Sjögren's Syndrome

Intervention / Treatment
-----------------
* Drug: hrIL-2 active
* Drug: hrIL-2 placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Experimental: hrIL-2 active<br>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 | Drug: hrIL-2 active<br>* 1 million U doses of human recombinant interleukin-2 s.c. injection active group: placebo group =1:1<br>* Other names: Human recombinant IL-2;|
| Placebo Comparator: Placebo Comparator: hrIL-2 placebo<br>1 million U doses of placebo s.c. injection | Drug: hrIL-2 placebo<br>* 1 million U doses of placebo s.c. injection active group: placebo group =1:1<br>* Other names: placebo;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Examination of the therapeutic effects (improvement in ESSDAI) of low dose IL-2 in patients with primary Sjögren's Syndrome |  | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunological Responses | 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 | 0,12,24weeks |