C3 (Complement Component 3) Glomerulopathy, IgA Nephropathy, Lupus Nephritis (LN)
Conditions
Keywords
Immunoglobulin A Nephropathy, Lupus Nephritis, Complement Component 3 Glomerulopathy, ADX-097, C3G
Brief summary
A Phase 2 Study to Evaluate the Safety, Pharmacodynamics, Pharmacokinetics, and Clinical Activity of ADX-097 Administered Subcutaneously in Male and Female Participants Aged 16 Years or Older with Immunoglobulin A Nephropathy (IgAN), Lupus Nephritis (LN), or Complement Component 3 Glomerulopathy (C3G)
Interventions
DRUGADX-097
Subcutaneous Infusions
Sponsors
Akebia Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants reporting treatment emergent adverse events (TEAEs) | Up to 30 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in urine protein-to-creatinine ratio (uPCR) | Baseline and up to 26 weeks | — |
| Change from baseline in estimated glomerular filtration rate (eGFR) | Baseline and up to 26 weeks | — |
| Trough plasma Concentration of ADX-097 | At Days 1, 8, 22, 50, 78, 106, 134 and 176 | Blood samples will be collected for the analysis of pharmacokinetic parameters at specified timepoints. |
Countries
Brazil, United States
Contacts
CONTACTAkebia Therapeutics
Outcome results
None listed