A Pilot-Study With Low-dose hrIL-2 for the Treatment of Systemic Lupus Erythematosus

NCT ID: NCT02465580

Last Updated: 2015-06-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-30
• Study Completion Date: 2017-12-31

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.

Conditions

Systemic Lupus Erythematosus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

hrIL-2 active

Intervention：Add hrIL-2 according to the protocol to original treatment. HrIL-2 active: 1 million U doses of human recombinant interleukin-2 s.c. injection

Group Type: ACTIVE_COMPARATOR

hrIL-2 active

Intervention Type: DRUG

active group: placebo group =1:1

hrIL-2 placebo

1 million U doses of placebo s.c. injection

Group Type: PLACEBO_COMPARATOR

hrIL-2 placebo

Intervention Type: DRUG

active group: placebo group =1:1

Interventions

hrIL-2 active

active group: placebo group =1:1

Intervention Type: DRUG

hrIL-2 placebo

active group: placebo group =1:1

Intervention Type: DRUG

Other Intervention Names

Human recombinant IL-2

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Monash University

OTHER

Sponsor Role: collaborator

Beijing ShuangLu Pharmaceutical Co., Ltd.

OTHER

Sponsor Role: collaborator

Peking University People's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Zhanguo Li

Dept. Rheumatology and Immunology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zhanguo Li, MD

Role: PRINCIPAL_INVESTIGATOR

Peking University Institute of Rheumatology and Immunology

Locations

Department of Rheumatology and Immunology, Peking University People's Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Tian Liu, MD

Role: CONTACT

mikle317@163.com

8613661345637

Jing He, MD

Role: CONTACT

hejing1105@126.com

8618611707347

Facility Contacts

Tian Liu, MD

Role: primary

mikle317@163.com

8613661345637

References

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.

Reference Type: DERIVED

PMID: 34116715 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33687069 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31537547 (View on PubMed)

Other Identifiers

hrIL-2-SLE

Identifier Type: -

Identifier Source: org_study_id