BEAM: Trial of Belimumab Combined With Multi-target Induction Therapy in Lupus Nephritis
Study Details
Study Description
Brief Summary
The goal of this single-center, prospective clinical trial is to test the safety and efficacy of belimumab combined with multi-target therapy in the treatment of severe lupus nephritis. The main questions it aims to answer are: lupus nephritis complete remission rate at week 24, and the partial remission rate and safety assessments. Patients with severe lupus nephritis will be enrolled and received pulse methylprednisolone at a dose of 1.5 to 3.0g, followed by intravenous belimumab at a dose of 10mg per kilogram at weeks 2, 4, and 6, and every 4 weeks thereafter. Multitarget therapy will be also administered during the induction phase. Induction therapy will last for 24 weeks. Patients with severe lupus nephritis who only received multi-target therapy during the same period will be enrolled as the control group.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Other: Belimumab and multi-target therapy group Patients with severe lupus nephritis will be enrolled and received pulse methylprednisolone at a dose of 1.5 to 3.0g, followed by intravenous belimumab at a dose of 10mg per kilogram at weeks 2, 4, and 6, and every 4 weeks thereafter. Multitarget therapy will be also administered during the induction phase. Induction therapy will last for 24 weeks. |
Drug: Methylprednisolone Injectable Suspension
Methylprednisolone pulse therapy, total dose from 1500mg to 3000mg.
Other Names:
Drug: Belimumab Injection
Belimumab at a dose of 10mg per kilogram at weeks 2, 4, and 6, and every 4 weeks for 24 weeks.
Other Names:
Drug: Immunosuppressive Agents
Mycophenolate Mofetil, oral, 1.0-1.5g per day;
Tacrolimus, oral, 2-4mg per day.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Proportion of patients with a cumulative complete response at week 24 of treatment. [24 weeks]
Complete response will be defined as below: urinary protein less than 0.4g/24h no active urinary sediment serum albumin more than 3.5g/dl and normal SCr.
Secondary Outcome Measures
- The proportion of patients with partial response and non-response to treatment. [24 weeks]
Partial response will be defined as a decrease of more than 50% of the baseline value of urinary protein and less than 3.5g/24h of urinary protein, a decrease of more than 50% of the baseline value of urinary sediment red blood cell count, and a normal or an increase of less than 30% of serum creatinine
- Overall response rate at 24 weeks. [24 weeks]
These will include complete remission and partial remission
- Improvement of clinical indicators. [24 weeks]
Clinical improvement of the disease was assessed using systemic lupus erythematosus disease activity index.
- The changes of B cells. [24 weeks]
The changes of CD20 number in peripheral blood will be observed and investigated.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Active LN in accordance with the American College of Rheumatology (ACR) diagnostic criteria for SLE (1997), SLE-DAI>10 points (except type Ⅴ LN).
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Patients with active lupus nephritis (type Ⅲ, Ⅳ, Ⅴ, Ⅴ+Ⅲ, Ⅴ+Ⅳ) diagnosed by light microscopy, immunofluorescence microscopy, and electron microscopy according to the ISN/RPS2003 lupus nephritis classification criteria, with pathological chronicity index (CI) less than 3 points and no TMA like changes in interstitial vessels.
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Proteinuria ≥1.5g/24h, with or without active urinary sediment (urinary sediment red blood cell count >100/ul, or white blood cell count >5 /HP, or red blood cell cast, excluding urinary tract infection).
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Serum creatinine <3.0mg/dL or eGFR<30 ml/min/1.73m^2 (CKD-EPI formula).
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Received methylprednisolone pulse therapy within 2 weeks before enrollment, cumulative dose 1.5-3.0g).
Exclusion Criteria:
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Required renal replacement therapy or received renal replacement therapy within 3 months.
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Abnormal liver function with elevated ALT, AST or bilirubin more than 2 times the upper limit of normal.
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Abnormal glucose metabolism, defined as fasting blood glucose concentration ≥7.0mmol/L and/or 2-hour postprandial blood glucose concentration >11.1mmol/L.
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Mycophenolate mofetil, cyclophosphamide, tacrolimus, cyclosporine A, and high-dose intravenous immunoglobulin (IVIG) were used in the past 12 weeks; It did not include oral hormones, azathioprine or tripterygium wilfordii polyglycosides, or intravenous low-dose MP (less than 80mg/ day), or short-term use of cyclosporine A<2 weeks, or leflunomide <4 weeks.
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Known allergy to or contraindication to MMF, tacrolimus, or belimumab; Patients with active infection or intravenous antibiotic use within 1 month before admission.
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Current or past 3 months: active hepatitis B, hepatitis C, tuberculosis, cytomegalovirus pneumonia, active fungal infection, syphilis infection or HIV infection, etc.; Active peptic ulcer; A history of drug use and alcohol abuse; Severe malnutrition (BMI<16 kg/m^2).
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Other active diseases, such as severe life-threatening cardiovascular diseases; Chronic obstructive pulmonary disease, or asthma requiring treatment with oral steroids; Bone marrow suppression caused by SLE activity was excluded: WBC<3000/ul, absolute neutrophil count <1300/ul, and platelet count < 50 000/ul. Patients with active SLE who received double plasma filtration, plasma exchange or high-dose gamma globulin therapy within 4 weeks.
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Patients with malignant hypertension.
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Women who have fertility requirements, refuse contraception or are lactating.
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Other investigators considered that they were not suitable for enrollment and may have rapid disease progression or severe disease complications.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Jiong Zhang | Nanjing | Jiangsu | China | 210016 |
Sponsors and Collaborators
- Nanjing University School of Medicine
Investigators
- Principal Investigator: Zhi-Hong Liu, MD, National Clinical Research Center of Kidney Diseases, Jinling Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NJCT-2023