Back to resultsEfficacy and Safety of Low-dose IL-2 in Patients With SLE: a Multicenter, Randomised, Placebo-controlled Trial
Primary Purpose
Systemic Lupus Erythematosus
Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Interleukin-2
Sponsored by
About this trial
This is an interventional treatment trial for Systemic Lupus Erythematosus
Eligibility Criteria
Inclusion Criteria:
- Meet the 1997 revised classification criteria of the American College of Rheumatology
- SLE disease activity index(SLEDAI) ≥ 8
- age:18 to 75 years, weight 45-80Kg
- Patients had an inadequate response to standard treatment for ≥ 3 months. The background treatment included corticosteroids (≤1.0 mg/kg), hydroxychloroquine, cyclophosphamide or mycophenolate mofetil
- Negative urine pregnancy test
- Written informed consent form
Exclusion Criteria:
- allergic to IL-2, corticosteroids, hydroxychloroquine, cyclophosphamide or mycophenolate mofetil
- active severe neuropsychiatric manifestations of SLE;
- hepatic insufficiency (alanine aminotransferase or aspartate aminotransferase ≥ 2 times of the upper limit of the normal range);
- pregnancy or lactation in females.
- Cancer or history of cancer cured for less than five years (except in situ carcinoma of the cervix or Basocellular carcinoma);
- Serious infection such as bacteremia, sepsis;history of chronic infection;
- active infection (hepatitis B or C virus, Epstein-Barr virus, human immunodeficiency virus or Mycobacterium tuberculosis);
- history vision and visual field disorders, cataract；
- severe comorbidities including heart failure (≥ grade III NYHA)
- active peptic ulcers；
- complicated with other autoimmune diseases;
- History of administration of rituximab or other biologics within 6 months;
- therapy with other immunosuppressors;
- participate in other clinical trial within 4 weeks;
Sites / Locations
- Peking University People's HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Placebo Comparator
Active Comparator
Active Comparator
Active Comparator
Arm Label
Placebo
IL-2 at 0.2MIU
IL-2 at 0.5MIU
IL-2 at 1.0MIU
Arm Description
placebo s.c. injection every other day for the first 12 weeks and then once a week for the second 12 weeks
0.2 MIU doses of IL-2 s.c. injection every other day for the first 12 weeks and then once a week for the second 12 weeks
0.5 MIU doses of IL-2 s.c. injection every other day for the first 12 weeks and then once a week for the second 12 weeks
1.0 MIU doses of IL-2 s.c. injection every other day for the first 12 weeks and then once a week for the second 12 weeks
Outcomes
Primary Outcome Measures
the response measured by the SLE Responder Index-4 (SRI-4)
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
Full Information
NCT ID
NCT04077684
First Posted
September 1, 2019
Last Updated
October 10, 2023
Sponsor
Peking University People's Hospital
1. Study Identification
Unique Protocol Identification Number
NCT04077684
Brief Title
Efficacy and Safety of Low-dose IL-2 in Patients With SLE: a Multicenter, Randomised, Placebo-controlled Trial
Official Title
Efficacy and Safety of Low-dose Interleukin-2 in Patients With Systemic Lupus Erythematosus: a Multicenter, Randomised, Placebo-controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 10, 2019 (Actual)
Primary Completion Date
August 31, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Peking University People's Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The management of active systemic lupus erythematosus (SLE) is challenging due to the heterogeneous nature of the disease and lack of specific treatment. Current treatment regimens mainly rely on corticosteroids and immunosuppressive agents which are associated with substantial adverse effects including various infections. Therefore, there is an unmet need for new therapies with better efficacy and less adverse effects.
Defective IL-2 production contributes to the unbalanced immune system in SLE. Previous short term open-labelled trials showed that low-dose IL-2 was efficient and tolerated in active SLE. It was suggested that low-dose IL-2 treatment promoted regulatory T cells (Treg) and inhibited T helper 17 cells (Th17) and follicular helper T cells (Tfh). The immunological rebalancing was associated with the induction of remission in SLE patients.
To establish that which low doses of IL-2 would be more efficacious and safe in active SLE, we carried out a multi-center, randomized, double-blind, placebo-controlled trial of three doses of IL2 (0.2 MIU, 0.5 MIU or 1 MIU) versus placebo.
Detailed Description
Active SLE patients at 18 to 75 years of age were enrolled. Patients were randomly assigned (in a 1:1:1:1 ratio) to one of the four arms (placebo or IL-2 at 0.2 MIU, 0.5 MIU or 1 MIU) in the study. IL-2 (0.2 MIU, 0.5 MIU or 1 MIU) or placebo was administered subcutaneously every other day for the first 12 weeks , and then was adjusted to once a week for the second 12 weeks. Follow-up visits occurred on weeks 4, 8,12,16,20 and 24. The end points were safety and clinical and immunologic response.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Systemic Lupus Erythematosus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
160 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
placebo s.c. injection every other day for the first 12 weeks and then once a week for the second 12 weeks
Arm Title
IL-2 at 0.2MIU
Arm Type
Active Comparator
Arm Description
0.2 MIU doses of IL-2 s.c. injection every other day for the first 12 weeks and then once a week for the second 12 weeks
Arm Title
IL-2 at 0.5MIU
Arm Type
Active Comparator
Arm Description
0.5 MIU doses of IL-2 s.c. injection every other day for the first 12 weeks and then once a week for the second 12 weeks
Arm Title
IL-2 at 1.0MIU
Arm Type
Active Comparator
Arm Description
1.0 MIU doses of IL-2 s.c. injection every other day for the first 12 weeks and then once a week for the second 12 weeks
Intervention Type
Drug
Intervention Name(s)
Interleukin-2
Other Intervention Name(s)
Human recombinant IL-2
Intervention Description
IL2 (0.2 MIU, 0.5 MIU or 1 MIU) : placebo = 1:1:1:1
Primary Outcome Measure Information:
Title
the response measured by the SLE Responder Index-4 (SRI-4)
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 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Meet the 1997 revised classification criteria of the American College of Rheumatology
SLE disease activity index(SLEDAI) ≥ 8
age:18 to 75 years, weight 45-80Kg
Patients had an inadequate response to standard treatment for ≥ 3 months. The background treatment included corticosteroids (≤1.0 mg/kg), hydroxychloroquine, cyclophosphamide , mycophenolate mofetil or other immunosuppressants.
Negative urine pregnancy test
Written informed consent form
Exclusion Criteria:
allergic to IL-2, corticosteroids, hydroxychloroquine, cyclophosphamide or mycophenolate mofetil
active severe neuropsychiatric manifestations of SLE;
hepatic insufficiency (alanine aminotransferase or aspartate aminotransferase ≥ 2 times of the upper limit of the normal range);
pregnancy or lactation in females.
Cancer or history of cancer cured for less than five years (except in situ carcinoma of the cervix or Basocellular carcinoma);
Serious infection such as bacteremia, sepsis;history of chronic infection;
active infection (hepatitis B or C virus, Epstein-Barr virus, human immunodeficiency virus or Mycobacterium tuberculosis);
history vision and visual field disorders, cataract；
severe comorbidities including heart failure (≥ grade III NYHA)
active peptic ulcers；
complicated with other autoimmune diseases;
History of administration of rituximab or other biologics within 6 months;
therapy with other immunosuppressors;
participate in other clinical trial within 4 weeks;
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xia Zhang
Phone
8615201303563
Email
haoxiamei@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Jing He
Phone
8618611707347
Email
hejing1105@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhanguo Li
Organizational Affiliation
Peking University Institute of Rheumatology and Immunology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Peking University People's Hospital
City
Beijing
ZIP/Postal Code
100044
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xia Zhang, MD
Email
haoxiamei@163.com
First Name & Middle Initial & Last Name & Degree
Jing He, MD
Email
hejing1105@126.com
First Name & Middle Initial & Last Name & Degree
Zhan-Guo Li, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Efficacy and Safety of Low-dose IL-2 in Patients With SLE: a Multicenter, Randomised, Placebo-controlled Trial
We'll reach out to this number within 24 hrs