The Efficacy and Safety of Biologics (Belimumab/ Telitacicept) Induction Therapy in Proliferative Lupus Nephritis Patients for 6 Months Compared With Mycophenolate Mofetil Treatment
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Complete Renal Response (CRR) Rate at Month 6
研究概览
简要总结
- 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).
- 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 14 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.Urine protein quantification > 1.0 g/d.
排除标准
- •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.
研究组 & 干预措施
Biologics Group
Glucocorticoids combined with a biologic agent (Belimumab or Telitacicept). All subjects receive oral glucocorticoids (starting dose 0.5 mg/kg/day, ≤40 mg/day, planned taper to ≤5 mg/day by Month 4). Combined with one biologic agent: Belimumab (IV infusion, 10 mg/kg/dose, every 2 weeks) or Telitacicept (subcutaneous injection, 160 mg/dose, once weekly). The specific biologic is chosen through discussion between the investigator and the patient. If no response after 3 months of induction therapy, subjects may switch to the Triple Therapy Group.
干预措施: Glucocorticoids (Drug)
Biologics Group
Glucocorticoids combined with a biologic agent (Belimumab or Telitacicept). All subjects receive oral glucocorticoids (starting dose 0.5 mg/kg/day, ≤40 mg/day, planned taper to ≤5 mg/day by Month 4). Combined with one biologic agent: Belimumab (IV infusion, 10 mg/kg/dose, every 2 weeks) or Telitacicept (subcutaneous injection, 160 mg/dose, once weekly). The specific biologic is chosen through discussion between the investigator and the patient. If no response after 3 months of induction therapy, subjects may switch to the Triple Therapy Group.
干预措施: belimumab (Biological)
Biologics Group
Glucocorticoids combined with a biologic agent (Belimumab or Telitacicept). All subjects receive oral glucocorticoids (starting dose 0.5 mg/kg/day, ≤40 mg/day, planned taper to ≤5 mg/day by Month 4). Combined with one biologic agent: Belimumab (IV infusion, 10 mg/kg/dose, every 2 weeks) or Telitacicept (subcutaneous injection, 160 mg/dose, once weekly). The specific biologic is chosen through discussion between the investigator and the patient. If no response after 3 months of induction therapy, subjects may switch to the Triple Therapy Group.
干预措施: Telitacicept (Biological)
Standard of Care (SOC) Group
Glucocorticoids combined with Mycophenolate Mofetil (Standard of Care regimen). All subjects receive the same oral glucocorticoid regimen as the Biologics Group. Combined with Mycophenolate Mofetil (MMF), target dose 1.5-2.0 g/day, administered orally in two divided doses. If no response after 3 months of induction therapy, subjects may switch to the Triple Therapy Group.
干预措施: Glucocorticoids (Drug)
Standard of Care (SOC) Group
Glucocorticoids combined with Mycophenolate Mofetil (Standard of Care regimen). All subjects receive the same oral glucocorticoid regimen as the Biologics Group. Combined with Mycophenolate Mofetil (MMF), target dose 1.5-2.0 g/day, administered orally in two divided doses. If no response after 3 months of induction therapy, subjects may switch to the Triple Therapy Group.
干预措施: Mycophenolate mofetil (MMF) (Drug)
Triple Therapy Group
Glucocorticoids combined with Mycophenolate Mofetil and a biologic agent (Belimumab or Telitacicept). All subjects receive the same oral glucocorticoid regimen as the other groups. Combined with Mycophenolate Mofetil (MMF) (target dose 1.5-2.0 g/day) and one biologic agent (Belimumab, every 2 weeks; or Telitacicept, once weekly). The specific biologic is chosen through discussion between the investigator and the patient. This group is both one of the initially randomized arms and the rescue therapy arm for non-responders from the other two groups.
干预措施: Glucocorticoids (Drug)
Triple Therapy Group
Glucocorticoids combined with Mycophenolate Mofetil and a biologic agent (Belimumab or Telitacicept). All subjects receive the same oral glucocorticoid regimen as the other groups. Combined with Mycophenolate Mofetil (MMF) (target dose 1.5-2.0 g/day) and one biologic agent (Belimumab, every 2 weeks; or Telitacicept, once weekly). The specific biologic is chosen through discussion between the investigator and the patient. This group is both one of the initially randomized arms and the rescue therapy arm for non-responders from the other two groups.
干预措施: belimumab (Biological)
Triple Therapy Group
Glucocorticoids combined with Mycophenolate Mofetil and a biologic agent (Belimumab or Telitacicept). All subjects receive the same oral glucocorticoid regimen as the other groups. Combined with Mycophenolate Mofetil (MMF) (target dose 1.5-2.0 g/day) and one biologic agent (Belimumab, every 2 weeks; or Telitacicept, once weekly). The specific biologic is chosen through discussion between the investigator and the patient. This group is both one of the initially randomized arms and the rescue therapy arm for non-responders from the other two groups.
干预措施: Telitacicept (Biological)
Triple Therapy Group
Glucocorticoids combined with Mycophenolate Mofetil and a biologic agent (Belimumab or Telitacicept). All subjects receive the same oral glucocorticoid regimen as the other groups. Combined with Mycophenolate Mofetil (MMF) (target dose 1.5-2.0 g/day) and one biologic agent (Belimumab, every 2 weeks; or Telitacicept, once weekly). The specific biologic is chosen through discussion between the investigator and the patient. This group is both one of the initially randomized arms and the rescue therapy arm for non-responders from the other two groups.
干预措施: Mycophenolate mofetil (MMF) (Drug)
结局指标
主要结局
Complete Renal Response (CRR) Rate at Month 6
时间窗: From Baseline to Month 6
Proportion of patients achieving Complete Renal Response. CRR is defined as: 24-hour urine protein \< 0.5 g/d, AND estimated glomerular filtration rate (eGFR) ≥ 85% of the baseline value, AND no receipt of rescue therapy or premature withdrawal from treatment.
次要结局
- Partial Renal Response (PRR) Rate at Months 1, 2, 3, 4, 5, and 6(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(From Baseline to Months 1, 2, 3, 4, 5, and 6)
- Time to Achieve Complete or Partial Renal Response(From randomization up to Month 6)
- Proportion of Patients with Renal-Related Events by Month 6(From Baseline to Month 6)
- Change from Baseline in 24-hour Urine Protein Quantification(Baseline, Months 1, 2, 3, 4, 5, and 6)
- Change from Baseline in Estimated Glomerular Filtration Rate(Baseline, Months 1, 2, 3, 4, 5, and 6)
- Incidence of Adverse Events During the Treatment Period(From first dose until 30 days after the last dose or the Month 6 visit, whichever is later)
研究者
Zhi-Hong Liu, MD
Professor
Nanjing University School of Medicine