Efficacy and Safety of Belimumab in SLE Patients

Efficacy and Safety of Belimumab for Prevention of Disease Flares in SLE Patients With Low Disease Activity

Systemic lupus erythematosus (SLE) is a chronic inflammatory systemic autoimmune disease. Recurrent relapses of disease and development of long-term organ damage are two key unsolved clinical problems. Belimumab is the only FDA-approved biological agent for SLE. Data showed that treatment with belimumab on the background of standard therapy was effective in active SLE patients. However, the efficacy of low-dose belimumab for prevention of disease flares in SLE patients with low disease activity is to be explored.

Study Overview

• Status: Recruiting
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Biological: Belimumab; Biological: Placebo

Detailed Description

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease with the incidence of about 70/100,000 in China. Recurrent relapses of disease and development of long-term organ damage are two key unsolved clinical problems. Its pathogenesis is still unclear, but B cells have been confirmed to play a vital role in it. Belimumab, a B-lymphocyte stimulating factor (Blys) inhibitor, was the only FDA-approved biological agent for SLE. BLISS-52 showed that more active lupus patients had their SELENA-SLEDAI score reduced by at least 4 points during 52 weeks with belimumab 10 mg/kg (58% vs 46%, p=0·0024) than with placebo. But there was limited data about belimumab in SLE patients with low disease activity. Our previous study indicated that even these patients still have an annual flare rate of 30-40%. Therefore, we try to explore whether low-dose of belimumab could prevent the disease flares in SLE patients with low disease activity.

• Study Type: Interventional
• Enrollment (Anticipated): 334
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Fangfang Sun; Phone Number: 86-021-34506393; Email: fiona_rj@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Shuang Ye, MD
      • Contact: Huijing Wang, postgraduate; Phone Number: +8618267851823; Email: whj30813@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18-70 years;
2. Patients with low disease activity (score≤ 6 at screening on SLEDAI); no British Isles Lupus Assessment Group (BILAG) A and no more than one B;
3. A stable treatment regimen with fixed doses of prednisone (≤ 20mg/day), antimalarial, or immunosuppressive drugs (azathioprine/mycophenolate mofetil/ methotrexate/ciclosporin/leflunomide/tacrolimus) for at least 30 days.
4. Sign the informed consent;

Exclusion Criteria:

1. Alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) > 2 times upper normal limits;
2. Creatinine clearance rate < 60ml/min;
3. Exposure to cyclophosphamide within past 6 months before screening;
4. Exposure to any B cell targeted therapy (Rituximab/belimumab) within past 1 year before screening;
5. History of Malignancy;
6. History of herpes zoster with past 3 months before screening.
7. Chronic HBV/HCV hepatitis；
8. Current infections (HIV/tuberculosis)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Belimumab 2mg/kg; Eligible patients were randomized in a 1:1 ratio to belimumab/placebo on the background of standard therapy. Belimumab 2mg/kg is administered intravenously at week 0, week 2, week 4 and then every 4 weeks until 48 weeks.	Biological: Belimumab; Belimumab 2mg/kg intravenously; Other Names: BENLYSTA™
Placebo Comparator: Placebo; Eligible patients were randomized in a 1:1 ratio to belimumab/placebo on the background of standard therapy. Placebo (normal saline) is administered intravenously at week 0, week 2, week 4 and then every 4 weeks until 48 weeks.	Biological: Placebo; Placebo intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with disease flares	Disease flare is defined by modified SELENA-SLEDAI SLE flare index (SFI).	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with mild/moderate flares	Disease flare is defined by modified SELENA-SLEDAI SLE flare index (SFI).	52 weeks
Percentage of patients with major flares	Disease flare is defined by modified SELENA-SLEDAI SLE flare index (SFI).	52 weeks
Time to first disease flare	Time to first disease flare	52 weeks
prednisone dose at each visit	compare the prednisone dose at each visit	52 weeks
SELENA-SLEDAI score at each visit	compare the disease activity measured by SELENA-SLEDAI score at each visit	52 weeks
BiLAG score at each visit	compare the disease activity measured by BILAG score at each visit	52 weeks
The percentage of patients achieving prednisone-free successfully	the percentage of patients achieving prednisone-free successfully	52 weeks
Number of participants with adverse events as assessed by CTCAE v4.0	the safety of belimumab	52 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subgroup analysis	subgroup analysis aiming to investigate which population will benefit most from belimumab with prespecified factors including age, gender, SLE duration, SELENA- SLEDAI, BILAG, PGA, serology, baseline LLDAS attainment and prednisone dose.	52 weeks

Collaborators and Investigators

• Sponsor: RenJi Hospital

Publications and helpful links

General Publications

• Navarra SV, Guzman RM, Gallacher AE, Hall S, Levy RA, Jimenez RE, Li EK, Thomas M, Kim HY, Leon MG, Tanasescu C, Nasonov E, Lan JL, Pineda L, Zhong ZJ, Freimuth W, Petri MA; BLISS-52 Study Group. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet. 2011 Feb 26;377(9767):721-31. doi: 10.1016/S0140-6736(10)61354-2. Epub 2011 Feb 4.
• Sun F, Huang W, Chen J, Zhao L, Zhang D, Wang X, Wan W, Dai SM, Chen S, Li T, Ye S. Low-dose belimumab for patients with systemic lupus erythematosus at low disease activity: protocol for a multicentre, randomised, double-blind, placebo-controlled clinical trial. Lupus Sci Med. 2022 Feb;9(1):e000638. doi: 10.1136/lupus-2021-000638.

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2021
• Primary Completion (Anticipated): March 1, 2023
• Study Completion (Anticipated): June 1, 2023

Study Registration Dates

• First Submitted: August 13, 2020
• First Submitted That Met QC Criteria: August 13, 2020
• First Posted (Actual): August 17, 2020

Study Record Updates

• Last Update Posted (Actual): June 9, 2022
• Last Update Submitted That Met QC Criteria: June 6, 2022
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Systemic Lupus Erythematosus; Belimumab; Disease flare
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Belimumab
• Other Study ID Numbers: Btrial

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No