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

N/ACompletedNCT02084238

Peking University People's Hospital40 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Systemic Lupus Erythematosus

Interventions

Interleukin-2DRUG

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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.

Locations (1)

Department of Rheumatology and Immunology, Peking University People's Hospital

Beijing, Beijing Municipality, China

Outcomes

Primary Outcomes

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.

Time frame: week 2，week 4，week 6，week 8，week 10

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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".

Time frame: 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.

Time frame: 24 weeks

Safety Assessment

Adverse events includes injection site reactions, influenza-like symptoms, infection, fever, tumor, cardiovascular event，drug-induced liver and kidney damage.

Time frame: up to Day 180

Data from ClinicalTrials.gov

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