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

Sponsor
Nanjing University School of Medicine (Other)
Overall Status
Recruiting
CT.gov ID
NCT05863936
Collaborator
(none)
15
1
1
21
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Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Methylprednisolone Injectable Suspension
  • Drug: Belimumab Injection
  • Drug: Immunosuppressive Agents
Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
15 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Clinical Trial of Belimumab Combined With Multi-target Induction Therapy in Adult Patients With Severe Lupus Nephritis
Actual Study Start Date :
Apr 1, 2023
Anticipated Primary Completion Date :
Mar 31, 2024
Anticipated Study Completion Date :
Dec 31, 2024

Arms and Interventions

Arm Intervention/Treatment
Other: 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.

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

    Primary Outcome Measures

    1. Proportion of patients with a cumulative complete response at week 24 of treatment. [24 weeks]

      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.

    Secondary Outcome Measures

    1. 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

    2. Overall response rate at 24 weeks. [24 weeks]

      These will include complete remission and partial remission

    3. Improvement of clinical indicators. [24 weeks]

      Clinical improvement of the disease was assessed using systemic lupus erythematosus disease activity index.

    4. The changes of B cells. [24 weeks]

      The changes of CD20 number in peripheral blood will be observed and investigated.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    14 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Jiong Zhang Nanjing Jiangsu China 210016

    Sponsors and Collaborators

    • Nanjing University School of Medicine

    Investigators

    • Principal Investigator: Zhi-Hong Liu, MD, National Clinical Research Center of Kidney Diseases, Jinling Hospital

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Zhi-Hong Liu, MD, Professor in Medicine, Nanjing University School of Medicine
    ClinicalTrials.gov Identifier:
    NCT05863936
    Other Study ID Numbers:
    • NJCT-2023
    First Posted:
    May 18, 2023
    Last Update Posted:
    May 18, 2023
    Last Verified:
    May 1, 2023
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Zhi-Hong Liu, MD, Professor in Medicine, Nanjing University School of Medicine
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of May 18, 2023