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

NCT04077684 | Completed Phase 2 DMC

• 1 other identifier: 2018PHB041-01
• Study Type: interventional
• Target: 152
• Locations: 1 country
• Sites: 1

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.

Conditions

Systemic Lupus Erythematosus

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (4)

Placebo

PLACEBO COMPARATOR

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

IL-2 at 0.2MIU

ACTIVE COMPARATOR

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

IL-2 at 0.5MIU

ACTIVE COMPARATOR

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

IL-2 at 1.0MIU

ACTIVE COMPARATOR

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

Interventions

Interleukin-2 DRUG

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

Also known as: Human recombinant IL-2

IL-2 at 0.2MIU; IL-2 at 0.5MIU; IL-2 at 1.0MIU; Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Peking University People's Hospital: lead

Study Sites (1)

Peking University People's Hospital

Beijing, 100044, China

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

Interleukin-2

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Study Officials

• Zhanguo Li

  Peking University Institute of Rheumatology and Immunology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dept. Rheumatology and Immunology

Study Record Dates

• First Submitted: September 1, 2019
• First Posted: September 4, 2019
• Study Start: September 10, 2019
• Primary Completion: March 7, 2024
• Study Completion: August 30, 2024
• Last Updated: December 3, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)