一项评估 ADX-097 在 IgAN、LN 或 C3G 受试者中的安全性、PD、PK 和临床活性的 2 期研究

Key Inclusion Criteria:

All participants

1. Male or female participants aged ≥16 years.

2. uPCR ≥0.5 g/g (from the average of 3 first morning voids [FMVs]).

3. Screening eGFR ≥30 mL/min/1.73m2 calculated by the Chronic Kidney Disease Epidemiology Collaboration creatinine equation (CKD-EPI GFR).

4. Participants receiving a renin-angiotensin-aldosterone system (RAAS) inhibitor, sodium-glucose cotransporter-2 (SGLT2) inhibitor, sparsentan, or atrasenten must have been on a stable dose (at the maximum recommended dose according to local guidelines or maximum tolerated dose) for at least 8 weeks prior to Study Day 1 and the dose is projected to remain stable until completion of the study.

   Participants with IgAN only

5. Kidney biopsy-proven diagnosis of IgAN with a kidney biopsy that is obtained within 10 years of Day 1 or within 5 years of Day 1 if the participant is known or suspected of also having diabetic nephropathy.

   Participants with LN only

6. Clinical diagnosis of systemic lupus erythematosus (SLE)

7. Kidney biopsy-proven diagnosis of LN with a kidney biopsy that is obtained within 24 weeks of Day 1.

8. Diagnosis of active focal or diffuse LN class III or IV

   Participants with C3G only

9. Kidney biopsy-proven diagnosis of C3G, either dense deposit disease (DDD) or complement component 3 glomerulonephritis (C3GN), with a kidney biopsy that is obtained within 52 weeks of Day 1.

10. Participants receiving mycophenolate mofetil (MMF) (or mycophenolic acid) or prednisone ≥10 mg/d or equivalent must have been on a stable dose for at least 12 weeks before Day 1 that is projected to remain stable until completion of the study.

Key Exclusion Criteria All participants

1. Rapidly progressive glomerulonephritis defined as a 50% decline in eGFR within 12 weeks of screening.

2. Concomitant significant renal disease other than IgAN, C3G, or LN per investigator discretion.

3. Participants with a history of and/or presence of anti-factor H antibodies at screening.

4. Uncontrolled hypertension with mean seated systolic blood pressure (BP) ≥160 mmHg or diastolic BP ≥100 mmHg based on the average of 2 measurements obtained at approximately 2-minute intervals after the individual has been sitting for 5 minutes.

5. Kidney, other solid organs, or bone marrow transplantation prior to or expected to occur during the study.

6. History of splenectomy.

   Participants with IgAN only

7. Secondary forms of IgAN

8. Received systemic corticosteroid therapy, oral budenoside, or any other form of immunosuppressive therapy within 12 weeks before Day 1.

   Participants with LN only

9. Lymphocyte count below 0.5 × 109/L at screening.

10. Received any of Cyclophosphamide, Calcineurin inhibitors, IV methylprednisolone, IV immunoglobulin therapy, Belimumab, Obinutuzumab and Rituximab treatments at protocol specified time points.

    Participants with C3G only

11. Evidence of monoclonal gammopathy of unclear significance, infections, malignancy, autoimmune diseases, or other conditions to which C3G is secondary.

12. Received systemic corticosteroid therapy, eculizumab, iptacopan, pegcetacoplan, or any other form of immunosuppressive therapy ≤12 weeks before Day 1, except for MMF (or mycophenolic acid), which is permitted.