Efficacy and Safety of Low-dose IL-2 in Patients With SLE: a Multicenter, Randomised, Placebo-controlled Trial

Efficacy and Safety of Low-dose Interleukin-2 in Patients With Systemic Lupus Erythematosus: a Multicenter, Randomised, Placebo-controlled Trial

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.

Study Overview

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

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.

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xia Zhang; Phone Number: 8615201303563; Email: haoxiamei@163.com
• Study Contact Backup: Name: Jing He; Phone Number: 8618611707347; Email: hejing1105@126.com

Study Locations

• China
  • Beijing, China, 100044
    • Recruiting
    • Peking University People's Hospital
    • Contact: Xia Zhang, MD; Email: haoxiamei@163.com
    • Contact: Jing He, MD; Email: hejing1105@126.com
    • Principal Investigator: Zhan-Guo Li, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Meet the 1997 revised classification criteria of the American College of Rheumatology
2. SLE disease activity index(SLEDAI) ≥ 8
3. age:18 to 75 years, weight 45-80Kg
4. 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.
5. Negative urine pregnancy test
6. Written informed consent form

Exclusion Criteria:

1. allergic to IL-2, corticosteroids, hydroxychloroquine, cyclophosphamide or mycophenolate mofetil
2. active severe neuropsychiatric manifestations of SLE;
3. hepatic insufficiency (alanine aminotransferase or aspartate aminotransferase ≥ 2 times of the upper limit of the normal range);
4. pregnancy or lactation in females.
5. Cancer or history of cancer cured for less than five years (except in situ carcinoma of the cervix or Basocellular carcinoma);
6. Serious infection such as bacteremia, sepsis;history of chronic infection;
7. active infection (hepatitis B or C virus, Epstein-Barr virus, human immunodeficiency virus or Mycobacterium tuberculosis);
8. history vision and visual field disorders, cataract；
9. severe comorbidities including heart failure (≥ grade III NYHA)
10. active peptic ulcers；
11. complicated with other autoimmune diseases;
12. History of administration of rituximab or other biologics within 6 months;
13. therapy with other immunosuppressors;
14. participate in other clinical trial within 4 weeks;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; placebo s.c. injection every other day for the first 12 weeks and then once a week for the second 12 weeks	Drug: Interleukin-2; IL2 (0.2 MIU, 0.5 MIU or 1 MIU) : placebo = 1:1:1:1; Other Names: Human recombinant IL-2
Active Comparator: IL-2 at 0.2MIU; 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	Drug: Interleukin-2; IL2 (0.2 MIU, 0.5 MIU or 1 MIU) : placebo = 1:1:1:1; Other Names: Human recombinant IL-2
Active Comparator: IL-2 at 0.5MIU; 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	Drug: Interleukin-2; IL2 (0.2 MIU, 0.5 MIU or 1 MIU) : placebo = 1:1:1:1; Other Names: Human recombinant IL-2
Active Comparator: IL-2 at 1.0MIU; 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	Drug: Interleukin-2; IL2 (0.2 MIU, 0.5 MIU or 1 MIU) : placebo = 1:1:1:1; Other Names: Human recombinant IL-2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	week 12

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2019
• Primary Completion (Estimated): August 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: September 1, 2019
• First Submitted That Met QC Criteria: September 1, 2019
• First Posted (Actual): September 4, 2019

Study Record Updates

• Last Update Posted (Actual): October 12, 2023
• Last Update Submitted That Met QC Criteria: October 10, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• 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: 2018PHB041-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No