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

Safety and Efficiency Study of Low-dose IL-2 Treatment in 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)).

Study Overview

• Status: Completed
• Conditions: Primary Sjögren's Syndrome
• Intervention / Treatment: Drug: hrIL-2 active; Drug: hrIL-2 placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Department of Rheumatology and Immunology, Peking University People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Collaborators: Monash University; Beijing ShuangLu Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Zhanguo Li, MD, PhD, Peking University Institute of Rheumatology and Immunology

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2015
• Primary Completion (Actual): March 31, 2017
• Study Completion (Actual): August 31, 2017

Study Registration Dates

• First Submitted: May 30, 2015
• First Submitted That Met QC Criteria: June 4, 2015
• First Posted (Estimate): June 8, 2015

Study Record Updates

• Last Update Posted (Actual): March 15, 2018
• Last Update Submitted That Met QC Criteria: March 13, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Eye Diseases; Disease; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Stomatognathic Diseases; Mouth Diseases; Lacrimal Apparatus Diseases; Arthritis, Rheumatoid; Xerostomia; Salivary Gland Diseases; Dry Eye Syndromes; Syndrome; Sjogren's Syndrome
• Other Study ID Numbers: hrIL-2-SS1