Lupus Nephritis, Remission, Safety Issues
Conditions
Keywords
Lupus nephritis, B cell depletion therapy, Remission
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.
Interventions
DRUGMethylprednisolone Injectable Suspension
Methylprednisolone pulse therapy, total dose from 1500mg to 3000mg.
Belimumab at a dose of 10mg per kilogram at weeks 2, 4, and 6, and every 4 weeks for 24 weeks.
DRUGImmunosuppressive Agents
1. Mycophenolate Mofetil, oral, 1.0-1.5g per day; 2. Tacrolimus, oral, 2-4mg per day.
Sponsors
Nanjing University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients with a cumulative complete response at week 24 of treatment. | 24 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
China
Contacts
Primary ContactJiong Zhang, PhD
Outcome results
None listed