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

Systemic Lupus Erythematosus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02084238
• Other study ID #: 2014-03
• Status: Completed
• Phase: N/A
• Start date: August 2013
• Est. completion date: October 2015

Study information

• Verified date: March 2020
• Source: Peking University People's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: October 2015
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Drug:
• Interleukin-2
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.

Locations

Country	Name	City	State
China	Department of Rheumatology and Immunology, Peking University People's Hospital	Beijing	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Peking University People's Hospital	Monash University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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