Efficacy and Immunological Evaluation of Belimumab Plus Low Dose IL-2 in the Treatment of Systemic Lupus Erythematosus

Systemic Lupus Erythematosus Clinical Trial

Official title:

Efficacy and Immunological Evaluation of Belimumab Plus Low Dose IL-2 in the Treatment of Systemic Lupus Erythematosus: a Randomised Prospective Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05262686
• Other study ID #: Peking2021SLE
• Status: Recruiting
• Phase: Phase 3
• Start date: April 1, 2022
• Est. completion date: June 1, 2023

Study information

• Verified date: March 2022
• Source: Peking University People's Hospital
• Contact: Ruiling Feng
• Phone: +86 18952390737
• Email: jsfeng001224[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study was to explore the clinical and immunological efficacy of belimumab plus low dose IL-2 in systemic lupus erythematosus.

Description:

Given that belimumab and low dose interleukin-2 (IL-2) have been widespreadly applied in the treatment of systemic lupus erythematosus (SLE), this study designed a randomised, single center, prospective study to investigate the effects and safety of combined utilization of belimumab and low dose IL-2. SLE patients were allocated in each group randomly (n=10) and regularly administered belimumab (10mg/kg) with or without IL-2 (1 million IU). Then, we evaluated the improvement of clinical and laboratory indexes and monitored the changes of immune cell subsets and cytokines.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: June 1, 2023
• Est. primary completion date: June 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• 1. Male or female >18 years of age at screening visits 2. Patients meet the American-European Consensus Group 2002 classification criteria 3. The patient must be informed in writing of the consent to participate in the trial and the patient is expected to be able to comply with the requirements of the study follow-up plan and other protocols.

4. Dosing of antimalarials, prednisone or equivalent, cholinergic stimulants, and topical cyclosporine required to be stable for at least 4 weeks before screening and during study;

maximum doses allowed:

• Hydroxychloroquine, 400 mg/day;
• Prednisone, 10 mg/day

Exclusion Criteria:

• 1. Any subject meeting any of the following criteria should be excluded: 1. Laboratory abnormality: • Hb=9 g/dl • Neutrophil 10 mg/d) within 1 month.

2. Serious complications: including heart failure (= New York Heart Association (NYHA) class III), renal insufficiency (creatinine clearance = 30 ml/min), liver dysfunction (serum Alanine transaminase (ALT) or aspartate aminotransferase (AST) greater than three times the upper limit of normal, or total bilirubin greater than Normal upper limit) 3. Known allergies, hyperreactivity or intolerance of tofacitinib or its excipients.

4. Have a serious infection needing hospitalization (including but not limited to hepatitis, pneumonia, bacteremia, pyelonephritis, Epstein-Barr virus (EBV), tuberculosis infection), or use intravenous antibiotics to treat infection in 2 months before the enrollment.

5. Infection with HIV (HIV antibody positive serology) or hepatitis C (Hep C antibody positive serology). If seropositive, it is recommended to consult a doctor who has expertise in treating HIV or hepatitis C virus infection.

6. Any known history of malignancy in the past 5 years (except for nonmelanoma skin cancer, non-melanoma skin cancer or cervical tumor without recurrence within 3 months after surgical cure prior to the first study preparation).

7. Uncontrolled mental or emotional disorders, including a history of drug and alcohol abuse over the past 3 years, may hinder the successful completion of the study.

8. Pregnant, lactating women (WCBP) are reluctant to use medically approved contraceptives during treatment and 12 months after treatment.

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Drug:
• Belimumab
Belimumab was intravenously administrated at a dose of 10mg/kg once a month for at least 24 weeks.
• Interleukin-2
Low lose interleukine-2 at a dose of 1 million IU was injected once every other day for 12 weeks, then the same dose of IL2 was injected once a week at the second stage for 12 weeks.

Locations

Country	Name	City	State
China	Department of Rheumatology and Immunology, Peking University People's Hospital	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking University People's Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Immunological responses of B cell subsets	A significant reduction of active B cell subsets including naive B cells and transitional B cells after different interventions. P values below 0.05 are considered statistically significant in this study.	Week 24
Secondary	Proportion of SLE Responder Index (SRI)4 response	SLE Responder Index (SRI)4 responders had =4-point reduction in safety of estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index(SELENA-SLEDAI) score	Week 12 and 24
Secondary	Prednisone dose	The improvement in prednisone dose experienced a mean corticosteroid dose reduction of =25% mg/day at baseline to =7.5 mg/day.	Week 12 and 24
Secondary	Immunoglobulin change from baseline	Serum samples were collected at indicated time-points for analysis of immunoglobulins: Immunoglobulin G (IgG), Immunoglobulin A (IgA), and Immunoglobulin M (IgM). Baseline is defined as the Day 0 visit from parent studies.	Week 12 and 24
Secondary	Autoantibody change from baseline	Blood samples were collected at indicated time-points for analysis of autoantibodies like anti-double stranded deoxyribonucleic Acid(dsDNA), antinuclear antibody (ANA). Baseline is defined as the Day 0 visit from parent studies.	Week 12 and 24
Secondary	Change of complement C3 and C4 Levels from baseline	Blood samples were collected at indicated time-points for analysis of complement levels like complement 3 (C3) and complement 4 (C4). Baseline is defined as the Day 0 visit from parent studies.	Week 12 and 24
Secondary	Safety and tolerability of the treatment	The incidence of adverse events, disease activity and clinical laboratory data throughout the study were accessed.	Up to Week 24