A Pilot-Study With Low-dose hrIL-2 for the Treatment of Systemic Lupus Erythematosus

Study Overview
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Brief Summary
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Dysfunction of regulatory T (Treg) cells has been detected in diverse autoimmune diseases, which can be promoted by interleukin-2 (IL-2). In a previous small sample trail performed by the investigator's group, the investigators found that the Low-dose IL-2 was effective and well tolerated in active SLE, and the effect was associated with selective modulation of CD4+ T cell subsets. This clinical study will confirm the efficacy and safety of low dose IL-2 treatment in SLE. The investigators perform a single-centre, double-blind pilot trial with hrIL-2 in SLE.The investigators evaluate the effectiveness and safeness of low-dose hrIL-2 for Systemic lupus erythematosus by randomized controlled study (hrIL-2 (N = 30) versus placebo group (N = 30)).

Detailed Description
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Each SLE patients (n=60) with Scores>=8 on SLEDAI 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 and clinical and immunologic response.

Official Title
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A Phase II Pilot-Study With Low-dose hrIL-2 for the Treatment of Systemic Lupus Erythematosus

Conditions
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Systemic Lupus Erythematosus

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


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，1997. 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. Negative urine pregnancy test. 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

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 24 | 
| Evaluation of the safety (type and number of adverse events and serious adverse events) of low-doseIL-2 in patients with SLE | Adverse events includes injection site reactions, influenza-like symptoms, infection, fever, tumor, cardiovascular event，drug-induced liver and kidney damage. | 24 weeks |