A pivotal Phase III, multicenter, randomized, double-blind, placebo-controlled study of the efficacy and safety of DMX-200 in patients with focal segmental glomerulosclerosis (FSGS) who are receiving an angiotensin II receptor blocker (ARB)
Focal segmental glomerulosclerosis
Current interventions as of 26/06/2025: Patients will receive either DMX-200 as 120 mg capsules taken orally twice daily (BID) or matching placebo capsules twice daily (BID), over a treatment period of up to 104 weeks. Patients will continue on a stable dose of angiotensin II receptor blocker (ARB) at the maximal tolerated dose and ≥50% of the maximum recommended dose as per the product label throughout the study as prescribed per standard of care. Post-treatment, there will be a 4-week follow-up period and patients will perform their final assessments at the End of Study (EOS) visit at week 108. Randomisation will be performed using an interactive response technology (IRT) system based on a predefined randomisation schedule. A randomisation blocking scheme (1:1 ratio) will be used to ensure that the balance between the treatment groups is maintained. The double-blind period will be followed by an open-label extension (OLE), which aims to assess the long-term efficacy and safety of DMX 200 for up to 2 additional years. The OLE period schedule involves participant visits to the site approximately every 6 months. Previous interventions: Patients will receive either DMX-200 as 120 mg capsules taken orally twice daily (BID) or matching placebo capsules twice daily (BID), over a treatment period of up to 104 weeks. Patients will continue on a stable dose of angiotensin II receptor blocker (ARB) at the maximal tolerated dose and ≥50% of the maximum recommended dose as per the product label throughout the study as prescribed per standard of care. Post-treatment, there will be a 4-week follow-up period and patients will perform their final assessments at the End of Study (EOS) visit at week 108. Randomisation will be performed using an interactive response technology (IRT) system based on a predefined randomisation schedule. A randomisation blocking scheme (1:1 ratio) will be used to ensure that the balance between the treatment groups is maintained.
Current participant inclusion criteria as of 26/06/2026: 1. Patients must be 12 to 80 years old. 2. Primary FSGS, genetic FSGS, or FSGS of undetermined cause (FSGS-UC). NOTE: Primary FSGS and FSGS-UC must be biopsy-proven within 7 years prior to Screening. The kidney biopsy could have been obtained at any time within the previous 7 years and should be based on light microscopy with supportive findings on either electron microscopy or immunofluorescence. No biopsy is required where there is a documented genetic mutation of a podocyte protein associated with FSGS. All patients should demonstrate a clinical history and disease course consistent with FSGS. 3. Must be either receiving a dose of an ARB at the maximal tolerated dose and ≥50% of the maximum recommended dose per the product label, or willing to transition to this treatment (including transition from an ACE inhibitor) prior to Stabilization. 4. If taking corticosteroids, the dosage must be ≤ 10mg / day prednisone (or equivalent) and stable for ≥4 weeks prior to and during both Screening and Stabilization, and there must be no plan to change their corticosteroid treatment regimen during the study. Use of inhaled corticosteroids for respiratory diseases is allowed. 5. If taking aldosterone inhibitors, mineralocorticoid receptor antagonists, direct renin inhibitors, sodium-glucose co-transporter-2 (SGLT2) inhibitors, or endothelin receptor antagonists (ERAs, including dual antagonists), the dose and regimen must be stable for ≥12 weeks prior to Screening and maintained during Stabilization and patients must have no plan to change their treatment regimen during the study. 6. Urine PCR >1.5 g/g (>169.5 mg/mmol) or 24-hour total protein >1.5 g/day based on 24-hour urine collection during both Screening and Qualification 7. Estimated GFR at screening: 7.1. For adults (≥ 18 yrs): eGFR ≥25 and ≤120 mL/min/1.73 m2 using the CKD Epidemiology Collaboration (CKD-EPI) Creatinine Equation (2009) 7.2. For adolescent Patients
Current participant exclusion criteria as of 26/06/2025: 1. Has FSGS secondary to another condition. 2. Patients with nephrotic syndrome (>3.5 g/day proteinuria and serum albumin <30 g/L) who have not previously been treated with standard of care FSGS-directed therapies (including steroids). 3. History of type 1 diabetes mellitus, or uncontrolled type 2 diabetes mellitus (defined as glycated hemoglobin [HbA1c] >8% at Screening) 4. History of lymphoma, leukemia, or any active malignancy within the past 2 years (except for basal cell or squamous cell carcinomas of the skin or cervical carcinoma in situ that have been resected and with no evidence of metastatic disease). 5. Active clinically significant hepatobiliary disease. 6. Documented history of heart failure (New York Heart Association Class III/IV) or a major adverse cardiac event within 12 weeks prior to Screening. 7. Has a physical, medical, or psychological condition, that in the opinion of the Investigator, may interfere with the evaluation the study. 8. The patient has a history of alcohol or illicit drug use disorder within 1 year prior to Screening. 9. Had a prior organ transplant or stem cell transplant, with the exception of corneal transplant. 10. Positive screening assessment for viral hepatitis B surface antigen, or anti-hepatitis C virus (HCV) antibody AND positive HCV RNA, or human immunodeficiency virus 1 and 2. 11. Serum potassium levels >5.5 mmol/L at Screening. 12. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >2 × upper limit of normal (ULN) at Screening. 13. Treatment with non-steroid immunosuppressant agents including biological drugs (e.g. rituximab), calcineurin inhibitors, cyclophosphamide, azathioprine, or mycophenolate mofetil within 12 weeks prior to Screening. 14. History of serious side effects or allergic response to an angiotensin II antagonist or has a known sensitivity to any components in the IP. 15. Unable to swallow oral medication. 16. Prior participatio