Low-dose IL-2( Interleukin-2) Treatment in SLE

Study Overview
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Brief Summary
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This clinical study will test the efficacy and safety of low dose IL-2 treatment in Systemic lupus erythematosus.

Detailed Description
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Systemic lupus erythematosus (SLE) is a chronic autoimmune syndrome affecting various organs. While available therapies, such as corticosteroids and immunosuppressive agents have improved the outcome of patients, there remains a significant unmet need for safe and more effective treatments. Dysfunction of regulatory T (Treg) cells has been detected in diverse autoimmune diseases, which can be promoted by interleukin-2 (IL-2). We hypothesized that low-dose IL-2 could be a novel therapy in active SLE patients. This is a single center, uncontrolled, open-label study to assess the efficacy/safety of low dose IL-2 plus standard therapy in active SLE. Methods: Each SLE patients (n=40) with Scores>=8 on the Safety of Estrogens in Lupus Erythematosus National Assessment (AELENA) version of the SLE Disease Activity Index (SLEDAI) that was refractory or relaps to glucocorticoid therapy received low-dose IL-2 (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 3-6 cycles according to the situation of the disease. The end points were safety and clinical and immunologic response. Expected Results: This trail will define low-dose IL-2 plus standard therapy is efficacy and safety with active lupus patients, which could be relevant to the amelioration the abnormity of T help cells in SLE patients.

Official Title
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Safety and Efficiency Study of Low-dose IL-2 Treatment in Systemic Lupus Erythematosus

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: Interleukin-2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet the American College of Rheumatology criteria for the diagnosis of SLE. Under standard treatment (≥ 2 months) at the time of inclusion Background treatment failed to control flares or to permit prednisone tapering With at least one of the following manifestations: thrombocytopenia, disease-associated rash, mouth ulcer, non-infectious type of fever, active vasculitis, renal disorder(proteinuria>0.5g/day), neuropsychiatric SLE. Positive for at least one of the following laboratory tests: ANA>1:160, anti-dsDNA, immunoglobulin>20g/L, decreased C3 or C4, leukopenia<3×10^9/L, thrombocytopenia<100×10^9/L; SLE disease activity index(SLEDAI) ≥ 8. Negative HIV test. Negative for hepatitis B and C virus. Written informed consent form. Exclusion Criteria: Sever chronic liver, kidney, lung or heart dysfunction; (heart failure (≥ grade III NYHA), hepatic insufficiency (transaminases> 3N) ) Serious infection such as bacteremia, sepsis; Cancer or history of cancer cured for less than five years (except in situ carcinoma of the cervix or Basocellular carcinoma); High-dose steroid pulse therapy (>1.5mg/kg) or IV bolus of corticosteroids in the last 2 months. History of administration of rituximab or other biologics; Purified protein derivative (tuberculin) >10mm Mental disorder or any other chronic illness or drug-abuse that could interfere with the ability to comply with the protocol or to give information; Inability to comply with IL-2 treatment regimen.

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interleukin-2<br>Interleukin-2 to treat activated SLE. | Drug: Interleukin-2<br>* Patients receive low dose recombinant human Interleukin-2（HrIL-2） (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 3-6 courses according to the situation of the disease.<br>* Other names: Recombinant Human Interleukin-2,125Ala, SL Pharm;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Were SLE Responders (SRI) | SRI response was defined as (1) a ≥ 4-point reduction in SELENA-SLEDAI score, (2) no new BILAG A score or ≤ 1 new BILAG B score, and (3) no deterioration from baseline in the physician's global assessment by ≥ 0.3 points. | week 2，week 4，week 6，week 8，week 10 | 

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. | week 0 and week 10 | 
| The Immunologic Impact of Low Dose IL-2 Treatment in SLE Patients | Laboratory measures were detected, including, C3, C4 and anti-dsDNA titres. | week 0 and week 10 | 
| SELENA SLEDAI Score | Assessment version of the SLE Disease Activity Index (SELENA-SLEDAI) change. The higher the score represent the worse of the disease. The total score ranges from 0 to 105 points, score> 8 means the disease is moderate-to-severe active. | week 0, week 10 | 
| Number of Relapses | Relapses mean that if the patient's SELENA SLEDAI Score is lower than 4 during the treatment, while the SELENA SLEDAI Score increase after stopping using the study drugs in 3 months. | 24 weeks | 
| Safety Assessment | Adverse events includes injection site reactions, influenza-like symptoms, infection, fever, tumor, cardiovascular event，drug-induced liver and kidney damage. | up to Day 180 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SLE, IL-2