Clinical trial NCT05863936: Trial of Belimumab Combined With Multi-target Induction Therapy in Lupus Nephritis
Official title: Clinical Trial of Belimumab Combined With Multi-target Induction Therapy in Adult Patients With Severe Lupus Nephritis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Lupus Nephritis
Remission
Safety Issues
Keywords: Lupus nephritis
B cell depletion therapy
Remission
Lead sponsor: Nanjing University School of Medicine
Sponsor class: OTHER
First posted: 2023-05-18
Enrollment: 15
Sex: ALL
Minimum age (years): 14
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Proportion of patients with a cumulative complete response at week 24 of treatment.
timeFrame: 24 weeks
Secondary outcomes:
measure: The proportion of patients with partial response and non-response to treatment.
timeFrame: 24 weeks
measure: Overall response rate at 24 weeks.
timeFrame: 24 weeks
measure: Improvement of clinical indicators.
timeFrame: 24 weeks
measure: The changes of B cells.
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Jiong Zhang
state: Jiangsu
Study officials:
affiliation: National Clinical Research Center of Kidney Diseases, Jinling Hospital
name: Zhi-Hong Liu, MD
role: PRINCIPAL_INVESTIGATOR
References: