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

Phase 2

Completed

• Conditions: Systemic Lupus Erythematosus
• Interventions: Drug: Interleukin-2

• Registration Number: NCT04077684
• Lead Sponsor: Peking University People's Hospital

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.

Study Timeline

• Study First Submitted: 2019-09-01
• Study First Submitted QC: 2019-09-01
• Study First Posted: 2019-09-04
• Study Start: 2019-09-10
• Primary Completion: 2024-03-07
• Study Completion: 2024-08-30
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-30
• Last Update Posted: 2024-12-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 152

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IL-2 at 0.2MIU	Interleukin-2	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
Placebo	Interleukin-2	placebo s.c. injection every other day for the first 12 weeks and then once a week for the second 12 weeks
IL-2 at 0.5MIU	Interleukin-2	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
IL-2 at 1.0MIU	Interleukin-2	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

Primary Outcome Measures

Name	Time	Method
the response measured by the SLE Responder Index-4 (SRI-4)	week 12	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.

Trial Locations

Locations (1)

Peking University People's Hospital; 🇨🇳 Beijing, China