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

Safety Issues Clinical Trial

— BEAM  

Official title:

Clinical Trial of Belimumab Combined With Multi-target Induction Therapy in Adult Patients With Severe Lupus Nephritis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05863936
• Other study ID #: NJCT-2023
• Status: Recruiting
• Phase: Phase 3
• Start date: April 1, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: May 2023
• Source: Nanjing University School of Medicine
• Contact: Jiong Zhang, PhD
• Phone: 86-25-80862860
• Email: jiongzhang[@]live.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: December 31, 2024
• Est. primary completion date: March 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 65 Years

Eligibility

Inclusion Criteria:

• Active LN in accordance with the American College of Rheumatology (ACR) diagnostic criteria for SLE (1997), SLE-DAI>10 points (except type ? LN).
• Patients with active lupus nephritis (type ?, ?, ?, ?+?, ?+?) 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.

Related Conditions & MeSH terms

• Lupus Nephritis
• Nephritis
• Remission
• Safety Issues

Intervention

Drug:
• Methylprednisolone Injectable Suspension
Methylprednisolone pulse therapy, total dose from 1500mg to 3000mg.
• Belimumab Injection
Belimumab at a dose of 10mg per kilogram at weeks 2, 4, and 6, and every 4 weeks for 24 weeks.
• Immunosuppressive Agents
Mycophenolate Mofetil, oral, 1.0-1.5g per day; Tacrolimus, oral, 2-4mg per day.

Locations

Country	Name	City	State
China	Jiong Zhang	Nanjing	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Nanjing University School of Medicine

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with a cumulative complete response at week 24 of treatment.	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.	24 weeks
Secondary	The proportion of patients with partial response and non-response to treatment.	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	24 weeks
Secondary	Overall response rate at 24 weeks.	These will include complete remission and partial remission	24 weeks
Secondary	Improvement of clinical indicators.	Clinical improvement of the disease was assessed using systemic lupus erythematosus disease activity index.	24 weeks
Secondary	The changes of B cells.	The changes of CD20 number in peripheral blood will be observed and investigated.	24 weeks