To Assess the Efficacy and Safety of Utilizing Galactose-deficient IgA1 Biomarker Changes to Guide Pathogenic IgA-targeted Therapeutic Strategies

Development and Validation of a Gd-IgA1 Guided Precision Therapy System for Targeted Therapeutic Strategies of IgA Nephropathy： An Open-label, Random Controlled Trial

The goal of this open-label, randomized study is to evaluate the efficacy and safety of the personalized treatment model in which Gd-IgA1 is dynamically monitored to guide medication adjustment in progressive IgAN patients treated with Nefecon or telitacicept.

Researchers will compare two groups of participants: those who have Gd-IgA1 checked regularly during treatment, and those who do not. This is to find out if regular Gd-IgA1 checks can help doctors adjust medication better and get better treatment results.

Study Overview

• Status: Recruiting
• Conditions: IgA Nephropathy (IgAN); Henoch Schönlein Purpura Nephritis
• Intervention / Treatment: Diagnostic test: Gd-IgA1 monitoring

Detailed Description

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and a leading cause of end-stage renal disease (ESRD) in young adults. Even with standard supportive care, many patients still experience worsening renal function and eventually develop ESRD.

The widely accepted multi-hit pathogenesis of IgAN recognizes the production of galactose-deficient IgA1 (Gd-IgA1) as the key step. Pathogenic Gd-IgA1 forms immune complexes that deposit in the kidney, triggering inflammation and renal damage, which serves as a target for new regimens.

Two novel targeted therapies have shown positive clinical effects for IgAN:

1. Budesonide Enteric Capsules (Nefecon): A gut-targeted oral preparation that releases drugs in the ileocecal region, reducing Gd-IgA1 production and renal immune deposition to protect renal function.
2. Telitacicept: A dual Blys/APRIL inhibitor that blocks the proliferation of B cells to reduce pathogenic Gd-IgA1 production.

However, the clinical effects of these novel therapies usually take time to appear (e.g., a significant drop in urinary protein with Nefecon is often seen 3 to 6 months after treatment). Early, sensitive indicators reflecting therapeutic effects are needed to enable timely adjustment of treatment plans.

Biomarkers (e.g., Gd-IgA1) decline earlier than urinary protein, which is highly significant for monitoring early treatment efficacy and optimizing personalized treatment decisions.

• Study Type: Interventional
• Enrollment (Estimated): 374
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yunfei Bao; Phone Number: 086-18500228190; Email: baoy_fei@163.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100010
      • Recruiting
      • Peking University First Hospital
      • Contact: Yunfei Bao; Phone Number: 086-18500228190; Email: baoy_fei@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male or female, between 18 and 75 years age;
• Biopsy confirmed diagnosis of primary IgA nephropathy or IgA Vasculitis-Associated Nephritis;
• Persistent proteinuria, defined as: two separate measurements (with an interval of ≥ 4 weeks) of 24-hour urinary protein excretion (24hUTP) ≥ 0.5 g/day, or urine protein-to-creatinine ratio (UPCR) ≥ 0.44 g/g;
• Estimated glomerular filtration rate (eGFR) (CKD-EPI) ≥ 30 ml/min per 1.73m^2;
• Have received the angiotensin converting enzyme Inhibitors(ACEI) / angiotensin receptor blocker(ARB) standard treatment for 4 weeks prior to randomization;
• Intending to receive or having received Nefecon or telitacicept treatment for ≤ 2 weeks at the time of screening.

Exclusion Criteria:

• Secondary IgA nephropathy (excluding IgA vasculitis) caused by ankylosing spondylitis, systemic lupus erythematosus, viral hepatitis, liver cirrhosis, etc.;
• With a known history or clinical evidence of concurrent renal diseases other than IgA nephropathy;
• Treating with systemic corticosteroids or immunosuppressants including cyclophosphamide, azathioprine, mycophenolate mofetil, tacrolimus, cyclosporine, rituximab, etc. within 3 months prior to randomizing;
• Have initiated or had a dose adjustment of leflunomide, tripterygium wilfordii or hydroxychloroquine within 3 months prior to randomizing;
• Active tuberculosis or latent carrier without treatment;
• Herpes zoster infected patients or patients with positive HIV antibody, positive HCV antibody or HBV infection (According to the HBV screening test, a) the HBsAg-positive; b) HBsAg-negative and HBcAb-positive, the HBV-DNA should be tested to determine the situation: the HBV-DNA positive subjects should be excluded, while the HBV-DNA negative subjects can participated in.)
• Suffering from following gastrointestinal diseases: gastric ulcer bleeding within the past 6 months, active inflammatory bowel disease, a history of major gastrointestinal surgery (e.g., gastrectomy, gastroenterostomy, or bowel resection), or pancreatic injury/pancreatitis within the past 6 months;
• A confirmed history of osteoporosis or osteonecrosis of the femoral head;
• Type 1 or type 2 diabetes with poor glycemic control (HbA1c > 8%);
• Body mass index (BMI) < 18.5 kg/m².;
• Systolic blood pressure (SBP) > 180 mmHg or diastolic blood pressure (DBP) > 110 mmHg;
• Decreased lymphocyte count (absolute value < 1.1 × 10⁹/L) or decreased immunoglobulin G (IgG < 6 g/L).
• Hepatic dysfunction, meeting any of the following: a) Child-Pugh Class C liver dysfunction; b) ALT or AST > 2 × upper limit of normal (ULN), or total bilirubin > 2 × ULN at screening; c) history of hepatic encephalopathy, esophageal varices, or portosystemic shunt surgery;
• Evidence of urinary tract obstruction or dysuria.
• A history of solid organ transplantation, hematopoietic stem cell/cell/bone marrow transplantation, or kidney transplantation.
• Pregnancy, lactation, female participants with childbearing plans during the trial or within 6 months of its completion, and male participants planning to conceive or donate sperm during the trial or within 3 months of its completion;
• With a history of malignant tumors within the past 5 years (excluding cutaneous squamous cell carcinoma or basal cell carcinoma);
• Allergy to human-derived biologics;
• Nephrotoxic drugs is unavoidable during the study period;
• Not suitable for the study judged by 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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Participants who have Gd-IgA1 checked regularly during treatment; Based on the combined results of reductions in urinary protein, Gd-IgA1 levels and other parameters, clinicians can thus evaluate early treatment efficacy and make timely medication adjustments - either continuing the original treatment, increasing the dose, or switching to another medication.	Diagnostic test: Gd-IgA1 monitoring; Participants in the experimental group will undergo a total of five Gd-IgA1 tests at baseline and during the follow-up period, and their clinicians will use these results to guide medication adjustment.
No Intervention: Participants who do not have Gd-IgA1 checked during treatment; Clinicians will make medication adjustment base on urinary protein and other laboratory test parameters if necessary.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean change in 24-hour proteinuria from baseline at the end of follow-up	From enrollment to the end of follow-up at 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change in 24-hour proteinuria from baseline at the midpoint of follow-up		From enrollment to the middle of follow-up period at 6 months
Change in estimated glomerular filtration rate (eGFR)	eGFR is calculated using the CKD-EPI method.	From enrollment to the end of follow-up at 12 months
Complete remission of proteinuria	24-hour urine total protein ≤ 0.3 g with a concurrent eGFR decline ≤ 30%	From enrollment to the midpoint of follow-up (6 months) and over the entire 12-month follow-up period
Immunosuppressant exposure measures	Cumulative dosage of non-corticosteroid immunosuppressants, cumulative dosage of systemic corticosteroids converted to prednisone-equivalent dosage, and number of corticosteroid bolus therapy courses during follow-up. Consecutive daily bolus doses count as one course; topical corticosteroids are excluded.	From enrollment to the end of follow-up at 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence rate and severity of adverse events	An adverse event is any undesirable experience associated with the study intervention in a patient.	From enrollment to the end of follow-up (12 months)

Collaborators and Investigators

• Sponsor: Hong Zhang

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: September 10, 2026
• First Submitted That Met QC Criteria: September 10, 2026
• First Posted (Actual): September 16, 2026

Study Record Updates

• Last Update Posted (Actual): September 16, 2026
• Last Update Submitted That Met QC Criteria: September 10, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: IgA Nephropathy; Gd-IgA1; IgA Vasculitis Nephritis
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Glomerulonephritis, IGA
• Other Study ID Numbers: 2025R0625; 2024YFC2511000 (Other Grant/Funding Number: China National Center for Biotechnology Development)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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