Clinical trial NCT04515719: Efficacy and Safety of Belimumab in SLE Patients
Official title: Efficacy and Safety of Belimumab for Prevention of Disease Flares in SLE Patients With Low Disease Activity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Systemic Lupus Erythematosus
Keywords: Belimumab
Systemic Lupus Erythematosus
Disease flare
Lead sponsor: RenJi Hospital
Sponsor class: OTHER
First posted: 2020-08-17
Enrollment: 231
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Percentage of patients with disease flares
timeFrame: 52 weeks
Secondary outcomes:
measure: Percentage of patients with mild/moderate flares
timeFrame: 52 weeks
measure: Percentage of patients with major flares
timeFrame: 52 weeks
measure: Time to first disease flare
timeFrame: 52 weeks
measure: prednisone dose at each visit
timeFrame: 52 weeks
measure: SELENA-SLEDAI score at each visit
timeFrame: 52 weeks
measure: BiLAG score at each visit
timeFrame: 52 weeks
measure: The percentage of patients achieving prednisone-free successfully
timeFrame: 52 weeks
measure: Number of participants with adverse events as assessed by CTCAE v4.0
timeFrame: 52 weeks
Other outcomes:
measure: Subgroup analysis
timeFrame: 52 weeks
Locations:
city: Shanghai
country: China
facility: Shuang Ye, MD
state: Shanghai
Study officials:
References:
citation: 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.
citation: 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.