Clinical trial NCT02465580: A Pilot-Study With Low-dose hrIL-2 for the Treatment of Systemic Lupus Erythematosus
Official title: A Phase II Pilot-Study With Low-dose hrIL-2 for the Treatment of Systemic Lupus Erythematosus
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Systemic Lupus Erythematosus
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
Collaborators: name: Monash University
name: Beijing ShuangLu Pharmaceutical Co., Ltd.
First posted: 2015-06-08
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Dysfunction of regulatory T (Treg) cells has been detected in diverse autoimmune diseases, which can be promoted by interleukin-2 (IL-2). In a previous small sample trail performed by the investigator's group, the investigators found that the Low-dose IL-2 was effective and well tolerated in active SLE, and the effect was associated with selective modulation of CD4+ T cell subsets.

This clinical study will confirm the efficacy and safety of low dose IL-2 treatment in SLE.

The investigators perform a single-centre, double-blind pilot trial with hrIL-2 in SLE.The investigators evaluate the effectiveness and safeness of low-dose hrIL-2 for Systemic lupus erythematosus by randomized controlled study (hrIL-2 (N = 30) versus placebo group (N = 30)).

Detailed description: Each SLE patients (n=60) with Scores\>=8 on SLEDAI received low-dose IL-2 or placebo (active group: placebo group =1:1, 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 cycles. The end points were safety and clinical and immunologic response.

Eligibility criteria: Inclusion Criteria:

* Meet the American College of Rheumatology criteria for the diagnosis of SLE，1997.
* 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.
* Negative urine pregnancy test.
* 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.

Primary outcomes:
measure: Number of Participants Who Were SLE Responders (SRI)
timeFrame: week 24
measure: Evaluation of the safety (type and number of adverse events and serious adverse events) of low-doseIL-2 in patients with SLE
timeFrame: 24 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Beijing
country: China
facility: Department of Rheumatology and Immunology, Peking University People's Hospital
state: Beijing
Study officials:
affiliation: Peking University Institute of Rheumatology and Immunology
name: Zhanguo Li, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Miao M, Xiao X, Tian J, Zhufeng Y, Feng R, Zhang R, Chen J, Zhang X, Huang B, Jin Y, Sun X, He J, Li Z. Therapeutic potential of targeting Tfr/Tfh cell balance by low-dose-IL-2 in active SLE: a post hoc analysis from a double-blind RCT study. Arthritis Res Ther. 2021 Jun 11;23(1):167. doi: 10.1186/s13075-021-02535-6.
citation: Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.
citation: He J, Zhang R, Shao M, Zhao X, Miao M, Chen J, Liu J, Zhang X, Zhang X, Jin Y, Wang Y, Zhang S, Zhu L, Jacob A, Jia R, You X, Li X, Li C, Zhou Y, Yang Y, Ye H, Liu Y, Su Y, Shen N, Alexander J, Guo J, Ambrus J, Lin X, Yu D, Sun X, Li Z. Efficacy and safety of low-dose IL-2 in the treatment of systemic lupus erythematosus: a randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 2020 Jan;79(1):141-149. doi: 10.1136/annrheumdis-2019-215396. Epub 2019 Sep 19.