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

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.

Study Overview

• Status: Recruiting
• Conditions: Systemic Lupus Erythematosus (SLE); Lupus Nephritis (LN)
• Intervention / Treatment: Drug: Glucocorticoids; Biological: belimumab; Biological: Telitacicept; Drug: Mycophenolate mofetil (MMF)

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhi-Hong Liu, MD; Phone Number: 86+025-80860218; Email: njrin@nju.edu.cn

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210016
      • Recruiting
      • Clinical Research Ethics Committee of the General Hospital of Eastern Theater Command of the People's Liberation Army
      • Contact: Zhi-Hong Liu, MD; Phone Number: 86+025-80860218; Email: njrin@nju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: 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).; Other Names: Corticosteroids; Biological: 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).; Other Names: Benlysta; Biological: 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.
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.	Drug: 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).; Other Names: Corticosteroids; Drug: 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.
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.	Drug: 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).; Other Names: Corticosteroids; Biological: 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).; Other Names: Benlysta; Biological: 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.; Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Renal Response (CRR) Rate at 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.	From Baseline to Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Partial Renal Response (PRR) Rate at Months 1, 2, 3, 4, 5, and 6	Proportion of patients achieving Partial Renal Response. PRR is defined as: ≥50% reduction in 24-hour urine protein from baseline, AND eGFR ≥ 85% of the baseline value, AND no receipt of rescue therapy or premature withdrawal from treatment.	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	Proportion of patients achieving Overall Renal Response. ORR is defined as achieving either Partial Renal Response (PRR) or Complete Renal Response (CRR).	From Baseline to Months 1, 2, 3, 4, 5, and 6
Time to Achieve Complete or Partial Renal Response	Time from randomization to the first achievement of either Complete Renal Response or Partial Renal Response.	From randomization up to Month 6
Proportion of Patients with Renal-Related Events by Month 6	Proportion of patients experiencing at least one renal-related event. Renal-related event is defined as: ① Death; ② Worsening proteinuria (≥50% increase in 24-hour urine protein from baseline AND value ≥3 g/g); ③ Worsening eGFR (≥30% decrease in eGFR from baseline AND value <60 mL/min/1.73 m²); ④ Receipt of rescue therapy.	From Baseline to Month 6
Change from Baseline in 24-hour Urine Protein Quantification	Absolute change and ratio from baseline in 24-hour urine protein (g/d) at each visit.	Baseline, Months 1, 2, 3, 4, 5, and 6
Change from Baseline in Estimated Glomerular Filtration Rate	Change from baseline in estimated glomerular filtration rate (eGFR, mL/min/1.73 m²) at each visit.	Baseline, Months 1, 2, 3, 4, 5, and 6
Incidence of Adverse Events During the Treatment Period	Proportion of patients experiencing at least one adverse event, serious adverse event, or adverse event of special interest (e.g., infusion/injection reactions, infections, new-onset hypertension/diabetes). Assessed based on abnormal findings in physical exams, vital signs, and laboratory tests (complete blood count, biochemistry, urinalysis).	From first dose until 30 days after the last dose or the Month 6 visit, whichever is later

Collaborators and Investigators

• Sponsor: Nanjing University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: December 25, 2025
• First Submitted That Met QC Criteria: January 13, 2026
• First Posted (Actual): January 14, 2026

Study Record Updates

• Last Update Posted (Actual): March 12, 2026
• Last Update Submitted That Met QC Criteria: March 10, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: SLE; Belimumab; Lupus Nephritis; Telitacicept; LN
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic; Lupus Nephritis; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Organic Chemicals; Fatty Acids; Lipids; Pharmacologic Actions; Chemical Actions and Uses; Acids, Acyclic; Carboxylic Acids; Caproates; Mycophenolic Acid; Glucocorticoids; Adrenal Cortex Hormones; belimumab; telitacicept
• Other Study ID Numbers: 2024LCYXXH009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: This study will share de-identified Individual Participant Data (IPD) to support further research. Shared datasets include: 1. Demographics & Baseline: Age, sex, SLE/LN duration, renal biopsy type (Ⅲ/Ⅳ±Ⅴ), baseline medication, SELENA-SLEDAI score. 2. Efficacy: 24h-proteinuria, eGFR, serum creatinine at baseline and months 1-6. 3. Safety & Immunology: ds-DNA, C3, C4; blood counts; liver/kidney function; all AEs/SAEs. 4. Treatment & Outcomes: Randomization, drug exposure (dose/duration), time to CRR/PRR, treatment failure or withdrawal. All data will be de-identified per HIPAA/GDPR, removing direct (name, ID) and indirect identifiers to prevent re-identification.
• IPD Sharing Time Frame: IPD and supporting information will become available for sharing after the primary results of this study are officially published (expected no later than June 2028). The data will be accessible for at least 5 years thereafter (i.e., until June 2033) to provide the research community with sufficient time for secondary analyses and validation. The access period may be extended according to the policies of the data hosting platform or the terms of the Data Use Agreement. The specific start date will be updated in this plan and on the clinical trial registration platform concurrently with the publication of the primary paper.

IPD Sharing Access Criteria

Access is open to researchers from academic or non-profit institutions for legitimate academic purposes. For-profit entities may apply for non-commercial use, subject to data protection regulations.

Approved researchers will access the de-identified IPD dataset (see Plan Description) and supporting documents (Study Protocol, SAP, ICF). Access is read-only; downloading or redistributing raw data is prohibited.

Access is controlled via formal application, including: a detailed research proposal (scientific value, objectives, methods), ethical approval or waiver, and a signed Data Use Agreement (DUA). The DUA prohibits re-identification, restricts use to approved analyses, and requires proper citation of the original study. Applications are reviewed by the Principal Investigator or institutional Data Access Committee. Approved users will access data through a secure, encrypted platform.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No