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

NCT ID: NCT04077684

Last Updated: 2024-12-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 152 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-10
• Study Completion Date: 2024-08-30

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.

Conditions

Systemic Lupus Erythematosus

Study Design

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

Study Groups

Placebo

placebo s.c. injection every other day for the first 12 weeks and then once a week for the second 12 weeks

Group Type: PLACEBO_COMPARATOR

Interleukin-2

Intervention Type: DRUG

IL2 (0.2 MIU, 0.5 MIU or 1 MIU) : placebo = 1:1:1:1

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

Group Type: ACTIVE_COMPARATOR

Interleukin-2

Intervention Type: DRUG

IL2 (0.2 MIU, 0.5 MIU or 1 MIU) : placebo = 1:1:1:1

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

Group Type: ACTIVE_COMPARATOR

Interleukin-2

Intervention Type: DRUG

IL2 (0.2 MIU, 0.5 MIU or 1 MIU) : placebo = 1:1:1:1

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

Group Type: ACTIVE_COMPARATOR

Interleukin-2

Intervention Type: DRUG

IL2 (0.2 MIU, 0.5 MIU or 1 MIU) : placebo = 1:1:1:1

Interventions

Interleukin-2

IL2 (0.2 MIU, 0.5 MIU or 1 MIU) : placebo = 1:1:1:1

Intervention Type: DRUG

Other Intervention Names

Human recombinant IL-2

Eligibility Criteria

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;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

Role: PRINCIPAL_INVESTIGATOR

Peking University Institute of Rheumatology and Immunology

Locations

Peking University People's Hospital

Beijing, , China

Countries

China

Other Identifiers

2018PHB041-01

Identifier Type: -

Identifier Source: org_study_id