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

• ClinicalTrials.gov Identifier: NCT04077684
• Recruitment Status: Recruiting
• First Posted: September 4, 2019
• Last Update Posted: March 27, 2020
• Sponsor: Peking University People's Hospital
• Information provided by (Responsible Party): Zhanguo Li, Peking University People's Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Systemic Lupus Erythematosus	Drug: Interleukin-2	Phase 2

Detailed Description:

Five hundred patients with active SLE 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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 500 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of Low-dose Interleukin-2 in Patients With Systemic Lupus Erythematosus: a Multicenter, Randomised, Placebo-controlled Trial
• Actual Study Start Date: September 10, 2019
• Estimated Primary Completion Date: August 31, 2024
• Estimated Study Completion Date: December 31, 2024

Arms and Interventions

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 Name: 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 Name: 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 Name: 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 Name: Human recombinant IL-2

Outcome Measures

Primary Outcome Measures :

1. the response measured by the SLE Responder Index-4 (SRI-4) [ Time Frame: 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.

Eligibility Criteria

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

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 or mycophenolate mofetil
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;

Contacts and Locations

Contacts

Contact: Xia Zhang; 8615201303563; haoxiamei@163.com

Contact: Jing He; 8618611707347; hejing1105@126.com

Locations

China

Peking University People's Hospital; Recruiting

Beijing, China, 100044

Contact: Xia Zhang, MD haoxiamei@163.com

Contact: Jing He, MD hejing1105@126.com

Principal Investigator: Zhan-Guo Li, MD

Sponsors and Collaborators

Peking University People's Hospital

Investigators

• Principal Investigator: Zhanguo Li; Peking University Institute of Rheumatology and Immunology

More Information

• Responsible Party: Zhanguo Li, Dept. Rheumatology and Immunology, Peking University People's Hospital
• ClinicalTrials.gov Identifier: NCT04077684
• Other Study ID Numbers: 2018PHB041-01
• First Posted: September 4, 2019
• Last Update Posted: March 27, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Lupus Erythematosus, Systemic; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Interleukin-2; Antineoplastic Agents; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs