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

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

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

Study Overview

• Status: Completed
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: Interleukin-2

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

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:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Interleukin-2; Interleukin-2 to treat activated SLE.	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.; Other Names: Recombinant Human Interleukin-2,125Ala, SL Pharm

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Collaborators: Monash University
• Investigators: Principal Investigator: Zhanguo Li, MD and PhD, Peking University Institute of Rheumatology and Immunology

Publications and helpful links

General Publications

• Liang K, He J, Wei Y, Zeng Q, Gong D, Qin J, Ding H, Chen Z, Zhou P, Niu P, Chen Q, Ding C, Lu L, Chen XX, Li Z, Shen N, Yu D, Deng J. Sustained low-dose interleukin-2 therapy alleviates pathogenic humoral immunity via elevating the Tfr/Tfh ratio in lupus. Clin Transl Immunology. 2021 Jun 1;10(6):e1293. doi: 10.1002/cti2.1293. eCollection 2021.

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (ACTUAL): November 1, 2014
• Study Completion (ACTUAL): October 1, 2015

Study Registration Dates

• First Submitted: March 8, 2014
• First Submitted That Met QC Criteria: March 9, 2014
• First Posted (ESTIMATE): March 11, 2014

Study Record Updates

• Last Update Posted (ACTUAL): April 3, 2020
• Last Update Submitted That Met QC Criteria: March 26, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: SLE, IL-2
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antineoplastic Agents; Interleukin-2
• Other Study ID Numbers: 2014-03