Which of the Commonly Available and Approved Drugs in Addition to Standard of Care Can Significantly Improve the Slope of Estimated Glomerular Filtration Rate at Two Years When Compared to Standard of Care Alone in South-Asian Kidney Biopsy-proven Adult (≥18 Years) Primary IgA Nephropathy?

Launched by CHRISTIAN MEDICAL COLLEGE, VELLORE, INDIA · Nov 4, 2024

Keywords

ClinConnect Summary

This clinical trial is investigating whether adding certain approved medications to the standard treatment can improve kidney function in adults with a specific kidney disease called IgA Nephropathy (IgAN). This condition is prevalent in South Asia and can lead to serious kidney problems over time. The trial will compare the effects of standard care, which includes certain blood pressure medications and diabetes drugs, with the addition of commonly used medications like low-dose steroids and other immune-modulating drugs. The goal is to see if these additional treatments can help protect kidney health over a two-year period.

To participate in the trial, adults aged 18 to 65 who have been diagnosed with IgAN and have specific kidney function levels may be eligible. Participants will need to provide written consent and be on a stable dose of certain medications before joining the study. Throughout the trial, participants can expect regular check-ups to monitor their kidney function and overall health. This research aims to find better long-term treatment options for IgAN, addressing an urgent need in South Asia where kidney disease is becoming increasingly common.

Gender

ALL

Eligibility 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 ≥45 mL/min/1.73 m2 or within the last ten years if eGFR \<45 mL/min/1.73 m2. If diabetic, the biopsy vintage should be less than five years.
• • 5. eGFR ≥20 mL/min/1.73 m2 at screening, as per the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
• • 6. Total urine protein excretion ≥1 g per 24-hour or UPCR ≥ 0.75 g/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/d of Dapagliflozin (SGLT2i) for at least 12 weeks at screening and from screening to study Day 1.
• • 8. Systolic blood pressure ≤140 mmHg and diastolic blood pressure ≤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:
• • 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 \<3g/dL AND UPCR \>3.5 g/g).
• • 3. Evidence of rapidly progressive glomerulonephritis defined as loss of ≥ 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 ≥ 40 kg/m2 at screening.
• • 9. Uncontrolled diabetes as defined by HbA1c \> 8% 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 and/or Ayurvedic medications within 12 weeks before screening.
• • Use of endothelin receptor antagonists/ oral spironolactone or oral finerenone/ GLP-1 agonists/ 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.