Trial of Belimumab Combined With Multi-target Induction Therapy in Lupus Nephritis (BEAM)

Nanjing University School of Medicine

Status and phase: Enrolling; Phase 3

Conditions: Remission; Lupus Nephritis; Safety Issues

Treatments: Drug: Methylprednisolone Injectable Suspension; Drug: Immunosuppressive Agents; Drug: Belimumab Injection

Study type: Interventional

Funder types: Other

Identifiers

NCT05863936

NJCT-2023

Details and patient eligibility

About

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.

Enrollment: 15 estimated patients

Sex: All

Ages: 14 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Active LN in accordance with the American College of Rheumatology (ACR) diagnostic criteria for SLE (1997), SLE-DAI>10 points (except type Ⅴ LN).
• 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.
• 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).
• Serum creatinine <3.0mg/dL or eGFR<30 ml/min/1.73m^2 (CKD-EPI formula).
• Received methylprednisolone pulse therapy within 2 weeks before enrollment, cumulative dose 1.5-3.0g).

Exclusion criteria

• Required renal replacement therapy or received renal replacement therapy within 3 months.
• Abnormal liver function with elevated ALT, AST or bilirubin more than 2 times the upper limit of normal.
• Abnormal glucose metabolism, defined as fasting blood glucose concentration ≥7.0mmol/L and/or 2-hour postprandial blood glucose concentration >11.1mmol/L.
• 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.
• Known allergy to or contraindication to MMF, tacrolimus, or belimumab; Patients with active infection or intravenous antibiotic use within 1 month before admission.
• 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).
• 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.
• Patients with malignant hypertension.
• Women who have fertility requirements, refuse contraception or are lactating.
• Other investigators considered that they were not suitable for enrollment and may have rapid disease progression or severe disease complications.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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15 participants in 1 patient group

Belimumab and multi-target therapy group

Other group

Description:

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.

Treatment:

Drug: Belimumab Injection

Drug: Immunosuppressive Agents

Drug: Methylprednisolone Injectable Suspension