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

Sponsor
Nanjing University School of Medicine
Study ID
NCT07340463
Phase
PHASE2
Status
Recruiting
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Conditions

  • Lupus Nephritis (LN)
  • Systemic Lupus Erythematosus (SLE)

Eligibility Criteria

Sex
ALL
Age
14 Years - 65 Years
Healthy Volunteers
Not accepted

Interventions

  • Glucocorticoids — DRUG
    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).
  • belimumab — BIOLOGICAL
    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).
  • Telitacicept — BIOLOGICAL
    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.
  • Mycophenolate mofetil (MMF) — DRUG
    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.

Study Details

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.

Key Dates

Start date
Dec 8, 2025
Status verified
Mar 2026
Primary completion
Jun 30, 2027
Completion
Jun 30, 2029

Study Design

Enrollment
50 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: 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.
  • Active Comparator: 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.
  • Experimental: 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.

Primary Outcome Measure

Complete Renal Response (CRR) Rate at Month 6 [ Time Frame: From Baseline to Month 6 ]

Central Contacts

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