Back to resultsLow-dose IL-2( Interleukin-2) Treatment in SLE
Primary Purpose
Systemic Lupus Erythematosus
Status
Completed
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Interleukin-2
Sponsored by
About this trial
This is an interventional treatment trial for Systemic Lupus Erythematosus focused on measuring SLE, IL-2
Eligibility Criteria
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.
Sites / Locations
- Department of Rheumatology and Immunology, Peking University People's Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Interleukin-2
Arm Description
Interleukin-2 to treat activated SLE.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
The Immunologic Impact of Low Dose IL-2 Treatment in SLE Patients
Laboratory measures were detected, including, C3, C4 and anti-dsDNA titres.
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".
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.
Safety Assessment
Adverse events includes injection site reactions, influenza-like symptoms, infection, fever, tumor, cardiovascular event，drug-induced liver and kidney damage.
Full Information
NCT ID
NCT02084238
First Posted
March 8, 2014
Last Updated
March 26, 2020
Sponsor
Peking University People's Hospital
Collaborators
Monash University
1. Study Identification
Unique Protocol Identification Number
NCT02084238
Brief Title
Low-dose IL-2( Interleukin-2) Treatment in SLE
Official Title
Safety and Efficiency Study of Low-dose IL-2 Treatment in Systemic Lupus Erythematosus
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
August 2013 (undefined)
Primary Completion Date
November 2014 (Actual)
Study Completion Date
October 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Peking University People's Hospital
Collaborators
Monash University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This clinical study will test the efficacy and safety of low dose IL-2 treatment in Systemic lupus erythematosus.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Systemic Lupus Erythematosus
Keywords
SLE, IL-2
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Interleukin-2
Arm Type
Experimental
Arm Description
Interleukin-2 to treat activated SLE.
Intervention Type
Drug
Intervention Name(s)
Interleukin-2
Other Intervention Name(s)
Recombinant Human Interleukin-2,125Ala, SL Pharm
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Participants Who Were SLE Responders (SRI)
Description
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 Outcome Measure Information:
Title
Immunological Responses
Description
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
Title
The Immunologic Impact of Low Dose IL-2 Treatment in SLE Patients
Description
Laboratory measures were detected, including, C3, C4 and anti-dsDNA titres.
Time Frame
week 0 and week 10
Title
SELENA SLEDAI Score
Description
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
Title
Number of Relapses
Description
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
Title
Safety Assessment
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhanguo Li, MD and PhD
Organizational Affiliation
Peking University Institute of Rheumatology and Immunology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Rheumatology and Immunology, Peking University People's Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100044
Country
China
12. IPD Sharing Statement
Citations:
PubMed Identifier
34094549
Citation
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.
Results Reference
derived
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Low-dose IL-2( Interleukin-2) Treatment in SLE
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