The Efficacy and Safety of Biologics (Belimumab/ Telitacicept) Induction Therapy in Proliferative Lupus Nephritis Patients for 6 Months Compared With Mycophenolate Mofetil Treatment

Обзор

1. Study Design This is a single-center, prospective, randomized, controlled, exploratory clinical trial. The study is designed to evaluate and compare the efficacy and safety of two biologic-based induction regimens against standard of care (SOC) and a triple-combination regimen in patients with active proliferative lupus nephritis (LN). 2. Study Objectives Primary Objective: To compare the 6-month complete renal response (CRR) rate among patients receiving biologic-based induction therapy, SOC induction therapy, and triple-combination induction therapy. Secondary Objectives: To compare the rates of partial renal response (PRR) and overall renal response (ORR) at monthly intervals up to Month 6; to assess the time to achieve CRR/PRR; to evaluate changes in clinical and immunological parameters from baseline; and to compare the safety profiles of the three treatment regimens. 3. Key Eligibility Criteria Patients aged 14-65 years with biopsy-proven active Class III or IV (±V) LN according to ISN/RPS 2018 classification, an SLE-DAI score \>6, and 24-hour urine protein \>1.0 g/d will be eligible. Key exclusion criteria include an eGFR ≥45 ml/min/1.73m², recent use of renal replacement therapy or potent immunosuppressive procedures, significant concurrent infections, severe hematological/ hepatic abnormalities, and known hypersensitivity to the study biologics. 4. Treatment Groups and Intervention Eligible patients will be randomized in a 2:2:1 ratio to one of three treatment arms for a 6-month induction period: Biologics Group (n≈20): Glucocorticoids + either Belimumab or Telitacicept. SOC Group (n≈20): Glucocorticoids + Mycophenolate Mofetil (MMF). Triple Therapy Group (n≈10): Glucocorticoids + MMF + either Belimumab or Telitacicept. The choice between Belimumab and Telitacicept within the Biologics and Triple Therapy groups will be determined jointly by the investigator and the patient. 5. Study Medications \& Administration Glucocorticoids: All patients will receive oral prednisone (or equivalent) starting at 0.5 mg/kg/day (max 40 mg/day), with a mandatory taper to ≤5 mg/day by Month 4 and stable dosing from Months 5-6. Intravenous methylprednisolone pulses are permitted per investigator discretion. Mycophenolate Mofetil (MMF): Administered only in the SOC and Triple Therapy groups. The target dose is 1.5-2.0 g/day, maintained until the end of the treatment period. Belimumab: Administered via intravenous infusion at 10 mg/kg (600 mg/dose) every 2 weeks. Telitacicept: Administered via subcutaneous injection at 160 mg once weekly. Patients in the Biologics or SOC groups showing no response by Month 3 may directly switch to the Triple Therapy regimen. 6. Primary Efficacy Endpoint The primary endpoint is the proportion of patients achieving Complete Renal Response (CRR) at Month 6. CRR is strictly defined as: 24-hour urine protein \<0.5 g/d, AND Estimated Glomerular Filtration Rate (eGFR) ≥85% of the baseline value, AND No requirement for rescue therapy or premature treatment withdrawal. 7. Secondary Efficacy \& Safety Assessments Key secondary efficacy assessments include monthly CRR, PRR, and ORR rates; time to response; incidence of renal-related events; and changes in proteinuria, eGFR, serum creatinine, and disease activity scores (SELENA-SLEDAI, BILAG-2004, PGA). Safety will be evaluated through the incidence and severity of adverse events, with special attention to infections, infusion/injection reactions, and metabolic parameters. 8\. Statistical Considerations This is an exploratory study with a planned enrollment of 40-50 patients. The primary analysis will use the Full Analysis Set (FAS) under the intention-to-treat principle. The difference in the Month 6 CRR rate among the three groups will be analyzed using the Chi-square test. Time-to-event data will be analyzed using the Kaplan-Meier method with Log-rank test for comparisons. 9\. Hypothesis: This study protocol outlines a head-to-head comparison of novel biologic-based induction strategies against current SOC for active LN. It aims to generate critical preliminary data on whether glucocorticoids combined with a biologic (Belimumab or Telitacicept) alone can induce effective renal remission, potentially offering a targeted treatment option with a different safety profile compared to conventional immunosuppressive therapy. The results may inform the design of larger, confirmatory trials in LN management.

Вмешательства

• Препарат Glucocorticoids
  Background therapy for all study arms. All subjects receive glucocorticoid therapy. The oral starting dose is prednisone 0.5 mg/kg/day (or equivalent), not exceeding 40 mg/day. Planned taper to ≤5 mg/day by Month 4, with stable dosing from Months 5-6. The tapering speed is determined by investigator assessment during the study. Permitted at investigator's discretion: intravenous methylprednisolone pulse therapy (dose 0.25-3.0g).
• Биопрепарат belimumab
  A humanized monoclonal antibody targeting B-cell activating factor (BAFF). Used in the "Biologics Group" and the "Triple Therapy Group". Administered via intravenous infusion every 2 weeks at a dose of 10 mg/kg (600mg/dose) for 6 months. Premedication with dexamethasone and antihistamines is required for the first infusion to prevent allergic reactions (dexamethasone may be omitted for subsequent infusions if no prior reaction).
• Биопрепарат Telitacicept
  A TACI-Fc fusion protein that neutralizes both BAFF and APRIL cytokines. Used in the "Biologics Group" and the "Triple Therapy Group". Administered via subcutaneous injection once weekly at a dose of 160mg for 6 months.
• Препарат Mycophenolate mofetil (MMF)
  An immunosuppressive agent. Used in the "Standard of Care (SOC) Group" and the "Triple Therapy Group". Administered orally in two divided daily doses, target dose 1.5-2.0 g/day. Maintained at the target dose until the end of the treatment period. Dose adjustment or brief interruption (preferably not exceeding 14 days) is permitted in case of specific hematologic toxicity or infectious complications.

Первичные конечные точки

• Complete Renal Response (CRR) Rate at Month 6 [Срок оценки: From Baseline to Month 6]

Вторичные конечные точки (7)

• Partial Renal Response (PRR) Rate at Months 1, 2, 3, 4, 5, and 6 [Срок оценки: From Baseline to Months 1, 2, 3, 4, 5, and 6]
• Overall Renal Response (ORR) Rate at Months 1, 2, 3, 4, 5, and 6 [Срок оценки: From Baseline to Months 1, 2, 3, 4, 5, and 6]
• Time to Achieve Complete or Partial Renal Response [Срок оценки: From randomization up to Month 6]
• Proportion of Patients with Renal-Related Events by Month 6 [Срок оценки: From Baseline to Month 6]
• Change from Baseline in 24-hour Urine Protein Quantification [Срок оценки: Baseline, Months 1, 2, 3, 4, 5, and 6]
• Change from Baseline in Estimated Glomerular Filtration Rate [Срок оценки: Baseline, Months 1, 2, 3, 4, 5, and 6]
• Incidence of Adverse Events During the Treatment Period [Срок оценки: From first dose until 30 days after the last dose or the Month 6 visit, whichever is later]

Критерии участия

Критерии включения

• 1.Signed written informed consent form. 2.Age 14-65 years (inclusive), any gender. 3.Meets the American College of Rheumatology (ACR) SLE diagnostic criteria (1997).

4.All patients have biopsy-confirmed class III/IV ± V LN within the past six months.

5.SLE-DAI score > 6. 6.Urine protein quantification > 1.0 g/d.

Критерии исключения

• 1.Estimated glomerular filtration rate (eGFR) ≥45 ml/min/1.73 m². 2.Patients who have received renal replacement therapy, plasma exchange, immunoadsorption, or high-dose intravenous immunoglobulin (100g) within the past 2 months.

3.Patients with concomitant critical organ damage or lupus crisis (e.g., pulmonary hemorrhage, encephalopathy, heart failure) deemed unsuitable for clinical trial participation by the investigator.

4.Hematological abnormalities: White blood cells <3000/μL, absolute neutrophil count <1500/μL, or lymphocytes <800/μL, platelet count <50,000/μL (unless due to SLE activity).

5.Liver function abnormalities: ALT, AST, or bilirubin levels exceeding 2 times the upper limit of normal.

6.Known allergy or contraindication to any component of belimumab and/or telitacicept.

7.Active infection or intravenous antibiotic use within 1 month prior to enrollment.

8.Pregnant or breastfeeding women. 9.Current or within the past 3 months: Active hepatitis B, hepatitis C, tuberculosis, cytomegalovirus pneumonia, active fungal infection, syphilis infection, or HIV infection; active peptic ulcer; history of drug abuse or alcoholism; severe malnutrition (BMI <16 kg/m²).

10.Other conditions: Severe cardiovascular disease potentially life-threatening; chronic obstructive pulmonary disease, or asthma/allergic diseases requiring long-term oral steroid treatment; malignant hypertension; history of malignancy within the past 5 years (except for completely treated basal cell or squamous cell skin cancer or cervical intraepithelial neoplasia).

11.Other situations deemed unsuitable for enrollment by the investigator.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Clinical Research Ethics Committee of the General Hospital of Eastern Theater Command of t — Нанкин

Идентификаторы

NCT: NCT07340463 · 2024LCYXXH009

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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