Dose-Ranging Safety, Tolerability, and Efficacy Study of AZD2373 in Participants With APOL1-Mediated Kidney Disease

Exclusion Criteria

• •Participants with diagnosis of Type 1 diabetes mellitus.
• •Body Mass Index \> 45 kg/m2.
• •SBP \> 180 mmHg/DBP \> 110 mmHg (measured when the participant is considered to be at steady state, and preferably when they have taken their BP medications that same day).
• •QTcF \> 470 ms.
• •Acute coronary syndrome/Acute myocardial infraction +/- coronary intervention with Percutaneous coronary intervention or Coronary artery bypass grafting within 6 months.
• •Transient ischaemic attack/ stroke within 3 months.
• •High second to third degree AV block or clinically significant sinus node dysfunction untreated with pacemaker.
• •A history of ventricular arrhythmias requiring treatment.
• •Participants with Type 2 diabetes mellitus must be excluded if ANY of the following conditions are present:
• •1. Current or any past use of insulin
• •2. Screening Haemoglobin A1c \> 8.0%
• •3. Receiving more than one oral anti-hyperglycaemic agent (excluding SGLT inhibitors which can be taken in addition to one other oral anti-hyperglycaemic agent).
• •Participant on kidney replacement therapy (dialysis or kidney transplant) or any other organ transplant.
• •History or serologic evidence of autoimmune-mediated glomerular disease including but not limited to: lupus nephritis (positive lupus serology), ANCA associated vasculitis (antineutrophil cytoplasmic antibody), membranous nephropathy (anti-phospholipase A2 receptor antibody or other autoantibody associated with membranous nephropathy), anti-GBM disease (anti-GBM antibody), or IgA nephropathy.
• •Another underlying cause of kidney disease that is not associated with APOL1, including but not limited to polycystic kidney disease or, congenital anomalies of the kidney and urinary tract.
• •History of a diagnosed coagulopathy, a major unexplained bleeding event, or other high-risk bleeding diathesis.