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

Launched by ASTRAZENECA · Feb 7, 2025

Keywords

ClinConnect Summary

This clinical trial is studying a new medication called AZD2373 to see how safe and effective it is for people with a specific type of kidney disease known as APOL1-Mediated Kidney Disease (AMKD). The researchers want to find out if AZD2373 can lower a measure called UACR, which helps indicate kidney health, more effectively than a placebo (a fake treatment) after 30 weeks of treatment. The trial is currently looking for participants aged between 18 and 65 who have certain high-risk genetic markers for this kidney disease and a specific level of UACR in their urine.

To join the trial, participants must not have certain conditions like Type 1 diabetes or severe heart issues, and they should have kidney function above a certain level. Those who qualify can expect to take either the study drug or a placebo, attend regular check-ups, and contribute to research that could help improve treatments for kidney disease in the future. It’s important for potential participants to understand the study requirements and to discuss any questions or concerns with their healthcare provider before enrolling.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Age: Male and female participants aged 18 to 65 years, inclusive at the time of informed consent.
• • Participants who have high-risk APOL1 genotype (G1/G1; G1/G2; G2/G2). The screening period can be extended if there are delays related to the shipment, handling, or processing of genotype results.
• • A geometric mean UACR ≥ 300 mg/g calculated based on the mean of readings taken from 3 FMV urine samples collected on 3 consecutive days. Since the mean will be assessed for eligibility, any of the 3 readings may fall below 300 mg/g.
• • eGFR ≥ 25 mL/min/1.73m2.
• • Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• • Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
• 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.