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

NCT ID: NCT05863936

Last Updated: 2023-05-18

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-01
• Study Completion Date: 2024-12-31

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.

Conditions

Lupus Nephritis; Remission; Safety Issues

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: OTHER

Methylprednisolone Injectable Suspension

Intervention Type: DRUG

Methylprednisolone pulse therapy, total dose from 1500mg to 3000mg.

Belimumab Injection

Intervention Type: DRUG

Belimumab at a dose of 10mg per kilogram at weeks 2, 4, and 6, and every 4 weeks for 24 weeks.

Immunosuppressive Agents

Intervention Type: DRUG

1. Mycophenolate Mofetil, oral, 1.0-1.5g per day;

2. Tacrolimus, oral, 2-4mg per day.

Interventions

Methylprednisolone Injectable Suspension

Methylprednisolone pulse therapy, total dose from 1500mg to 3000mg.

Intervention Type: DRUG

Belimumab Injection

Belimumab at a dose of 10mg per kilogram at weeks 2, 4, and 6, and every 4 weeks for 24 weeks.

Intervention Type: DRUG

Immunosuppressive Agents

1. Mycophenolate Mofetil, oral, 1.0-1.5g per day;

2. Tacrolimus, oral, 2-4mg per day.

Intervention Type: DRUG

Other Intervention Names

Methylprednisolone pulse therapy; Beliumab induction therapy; Multi-target immunosuppressive therapy

Eligibility Criteria

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.

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nanjing University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Zhi-Hong Liu, MD

Professor in Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zhi-Hong Liu, MD

Role: PRINCIPAL_INVESTIGATOR

National Clinical Research Center of Kidney Diseases, Jinling Hospital

Locations

Jiong Zhang

Nanjing, Jiangsu, China

Site Status: RECRUITING

Countries

China

Central Contacts

Jiong Zhang, PhD

Role: CONTACT

jiongzhang@live.com

86-25-80862860

Facility Contacts

Jiong Zhang, PhD

Role: primary

jiongzhang@live.com

86-13951883235

Other Identifiers

NJCT-2023

Identifier Type: -

Identifier Source: org_study_id