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

NCT05863936 | Unknown Phase 3

• 1 other identifier: NJCT-2023
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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

Keywords

Lupus nephritis; B cell depletion therapy; Remission

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with a cumulative complete response at week 24 of treatment.

  Complete response will be defined as below: 1. urinary protein less than 0.4g/24h 2. no active urinary sediment 3. serum albumin more than 3.5g/dl 4. and normal SCr.

  24 weeks

Secondary Outcomes (4)

• The proportion of patients with partial response and non-response to treatment.

  24 weeks

• Overall response rate at 24 weeks.

  24 weeks

• Improvement of clinical indicators.

  24 weeks

• The changes of B cells.

  24 weeks

Study Arms (1)

Belimumab and multi-target therapy group

OTHER

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; Drug: Belimumab Injection; Drug: Immunosuppressive Agents

Interventions

Methylprednisolone Injectable Suspension DRUG

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

Also known as: Methylprednisolone pulse therapy

Belimumab and multi-target therapy group

Belimumab Injection DRUG

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

Also known as: Beliumab induction therapy

Belimumab and multi-target therapy group

Immunosuppressive Agents DRUG

1. Mycophenolate Mofetil, oral, 1.0-1.5g per day; 2. Tacrolimus, oral, 2-4mg per day.

Also known as: Multi-target immunosuppressive therapy

Belimumab and multi-target therapy group

Eligibility Criteria

• Age: 14 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Nanjing University School of Medicine: lead

Study Sites (1)

Jiong Zhang

Nanjing, Jiangsu, 210016, China

RECRUITING

MeSH Terms

Conditions

Lupus Nephritis

Interventions

belimumab; Immunosuppressive Agents

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lupus Erythematosus, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunologic Factors; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Zhi-Hong Liu, MD

  National Clinical Research Center of Kidney Diseases, Jinling Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jiong Zhang, PhD

CONTACT

86-25-80862860; jiongzhang@live.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor in Medicine

Study Record Dates

• First Submitted: April 19, 2023
• First Posted: May 18, 2023
• Study Start: April 1, 2023
• Primary Completion: March 31, 2024
• Study Completion: December 31, 2024
• Last Updated: May 18, 2023

Record last verified: 2023-05

Locations

CN (1)