Health Condition 1: N033- Chronic nephritic syndrome with diffuse mesangial proliferative glomerulonephritis
Conditions
Interventions
Intervention1: SoC and Oral prednisolone.
This intervention arm will start with randomisation of the first participant.: Oral prednisolone and SoC
Oral prednisolone 0.5 mg per kg per day (maximum, 40
Sponsors
Suceena Alexander
Eligibility
Inclusion criteria
Inclusion criteria: 1. Must be able to provide a written informed consent form, which must be obtained before the initiation of study assessments. 2. Adults between 18-65 years of age. 3. Males or Females. 4. Diagnosis of primary IgAN as demonstrated by renal biopsy of any vintage if eGFR greater than or equal to 45 mL per min per 1.73 m2 or within the last ten years if eGFR less than 45 mL per min per 1.73 m2. If diabetic, the biopsy vintage should be less than five years. 5. eGFR greater than or equal to 20 mL/min/1.73 m2 at screening, as per the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. 6. Total urine protein excretion greater than or equal to 1 g per 24-hour or UPCR greater than or equal to 0.75 g per g from an adequately measured 24-hour urine sample (24HUP) during the Screening Period. 7. Patient on the maximum labelled or tolerated dose of ACEi or ARB AND 10mg per day of Dapagliflozin (SGLT2i) for at least 12 weeks at screening and from screening to study Day 1. 8. Systolic blood pressure less than or equal to 140 mmHg and diastolic blood pressure less than or equal to 90 mmHg at randomisation. Other anti-hypertensives can be optimised during the screening period to achieve the BP goal. 9. A female is eligible if she is not pregnant and consents to avoid pregnancy during the study duration.
Exclusion criteria
Exclusion criteria: 1. IgAN secondary to another condition (e.g., liver cirrhosis) or other causes of mesangial IgA deposition such as systemic lupus erythematosus (SLE), dermatitis herpetiformis, ankylosing spondylitis, etc. IgA vasculitis (i.e., Henoch-Schonlein purpura) with biopsy-proven mesangial IgA deposition and no active skin vasculitis for the last year can be included. 2. Evidence of nephrotic syndrome at screening (serum albumin less than 3g per dL AND UPCR greater than 3.5 g per g). 3. Evidence of rapidly progressive glomerulonephritis defined as loss of greater than or equal to 50% of eGFR in three months before screening. 4. Concomitant kidney disease in addition to IgAN in kidney biopsy (e.g., diabetic nephropathy, primary focal segmental glomerulosclerosis, membranous nephropathy, C3 glomerulopathy, lupus nephritis). 5. Female patients planning pregnancy. 6. Concomitant co-morbidities like systemic autoimmune disorders, chronic active infections like tuberculosis, hepatitis B, hepatitis C and human immunodeficiency virus infection, chronic liver disease, and chronic obstructive pulmonary disease. 7. Renal or other organ transplantation before, or expected during, the study, except for corneal transplants. 8. Morbid obesity defined as BMI greater than or eual to 40 kg per m2 at screening. 9. Uncontrolled diabetes as defined by HbA1c greater than 8 percentage at screening. 10. History or diagnosis of demyelinating diseases such as multiple sclerosis or optic neuritis. 11. Prohibited medications: • Participants who received oral steroids over two weeks within 12 weeks before screening. • Immunosuppressive medications (e.g., MMF, azathioprine, cyclophosphamide, hydroxychloroquine) for treating IgAN within 12 weeks before screening. • Use of B-cell–directed biologic therapies, including belimumab, rituximab, and ocrelizumab, within six months before screening. • Use of other biologics (e.g., anti-TNF, abatacept, anti-IL-6) and investigational biologics within the last four weeks or five half-lives, whichever is longer, before the screening. • Use of traditional medications or Ayurvedic medications within 12 weeks before screening. • Use of endothelin receptor antagonists or oral spironolactone or oral finerenone or GLP-1 agonists or hydroxychloroquine within 12 weeks before screening. 12. Patients with a history of unstable angina, Class III and IV congestive heart failure, and clinically significant arrhythmia, as judged by the Investigator. 13. Active clinically significant viral, bacterial, or fungal infection or any major episode of infection requiring hospitalisation or treatment with parenteral anti-infectives within four weeks before or during the Screening Visit. 14. History of malignancy within the past five years before Screening (except for adequately treated basal cell carcinoma or non-metastatic squamous cell carcinoma of the skin or cervical carcinoma in situ, with no evidence of recurrence). 15. Known hypersensitivity to any of the interventions. 16. Major surgery within six weeks before the Screening Visit. 17. Clinically significant history of alcohol or drug abuse in the one year before the Screening Visit as per the Investigator’s opinion. 18. Unwillingness or lack of capacity to follow all study procedures.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the mean change in annualized eGFR slope (ml per min per 1.73m2) in the interventional and the active comparator arms. Timepoint: Baseline, 3, 6, 9, 12, 15, 18 and 24 months. | — |
Secondary
| Measure | Time frame |
|---|---|
| To evaluate the mean change in UPCR ratio in the interventional and the active comparator arms.Timepoint: Baseline, 6, 12, 18 and 24 months.;To evaluate the mean change in time averaged proteinuria in the interventional and the active comparator arms.Timepoint: Baseline, 6, 12, 18 and 24 months.;Proportion of participants reaching the composite endpoint. Composite end-point is defined as greater than or equal to 50 percent decline in eGFR sustained for at least 28 days, end-stage kidney disease requiring renal replacement therapy, or death.Timepoint: From enrollment to the end of treatment at 24 months.;Proportion of participants having rapidly progressive kidney disease. Rapidly progressive kidney disease is defined as greater than or equal to 50 percent decline in eGFR over three months.Timepoint: From enrollment to the end of treatment at 24 months.;Proportion of participants reaching eGFR less than 15 ml per min per 1.73 m2 sustained for at least 28 daysTimepoint: From enrollment to the end of treatment at 24 months.;Adverse Events. Percentage adverse events in clinical and laboratory tests.Timepoint: From enrollment to the end of treatment at 24 months.;Glucocorticoid Toxicity Index. Change in Glucocorticoid Toxicity Index (GTI) score for prednisolone and budesonide arms.Timepoint: Baseline, 6months, 12 months.;Medication Adherence. To evaluate the proportion of participants with Medication Adherence in the interventional and the active comparator arms.Timepoint: From enrollment to the end of treatment at 24 months;To evaluate participant related outcome measure (PROM) by EQ-5D-5L study instrument.Timepoint: Baseline, 12 and 24 months.;To evaluate PROM by KDQOL-36 study instrument.Timepoint: Baseline, 12 and 24 months.;To evaluate PROM py FACIT-F study instrument.Timepoint: Baseline, 12 and 24 months.;Serum biomarker profile. To evaluate the longitudinal change in serum biomarker profile from baseline to two years. This is an exploratory objective and the bio s | — |
Countries
India
Contacts
Public ContactSuceena Alexander
Christian Medical College Vellore
Outcome results
None listed