Henoch Schönlein Purpura Nephritis, IgA Nephropathy (IgAN)
Conditions
Keywords
IgA Nephropathy, IgA Vasculitis Nephritis, Gd-IgA1
Brief summary
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.
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.
Interventions
DIAGNOSTIC_TESTGd-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.
Sponsors
Hong Zhang
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) | From enrollment to the end of follow-up at 12 months | eGFR is calculated using the CKD-EPI method. |
| Complete remission of proteinuria | From enrollment to the midpoint of follow-up (6 months) and over the entire 12-month follow-up period | 24-hour urine total protein ≤ 0.3 g with a concurrent eGFR decline ≤ 30% |
| Immunosuppressant exposure measures | From enrollment to the end of follow-up at 12 months | 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. |
Countries
China
Contacts
CONTACTYunfei Bao
Outcome results
None listed