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NCT06824987PHASE2Recruiting

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

AstraZeneca

Start Date

3/5/2025

Completion Date

8/30/2027

Summary

The purpose of this study is to assess the efficacy and safety of AZD2373 in participants diagnosed with APOL1-Mediated Kidney Disease (AMKD) who are homozygotes or compound heterozygotes for APOL1 high-risk genotypes (G1 and G2). The primary hypothesis to be evaluated is that AZD2373, compared with placebo, will result in a greater reduction in UACR as assessed by the relative change from Baseline in UACR at Week 30.

Detailed Description

This is a Phase 2b study to assess efficacy and safety of AZD2373 involving 3 study treatment arms in Part A and 2 study treatment arms in Part B where participants and study personnel including study investigators are blinded to the assigned treatment. Participants with 300 mg/g or greater UACR and eGFR ≥ 25mL/min/1.73m2 will be recruited into the study. Participants on kidney replacement therapy (dialysis or kidney transplant) or any other organ transplant will be excluded. The study will have Part A and Part B. Part A (n = 96) will have a 1:1:1 randomization of participants to subgroups receiving weekly subcutaneous injections of 50 mg AZD2373, 150 mg AZD2373, and placebo. Part B (n = 40) will have a 4:1 randomization of participants to subgroups receiving every other week subcutaneous injections of 150 mg or placebo. Part B will begin after Part A is completely enrolled. Both Part A and Part B will have same participant criteria and schedules. The SoA and visit schedule will not change for Part B. All participants will remain in the study on treatment until the last participant has completed 30 weeks of treatment. The treatment duration will be up to minimum of 30 weeks of study treatment. All participants will have the opportunity to enter the OLE study.

Eligibility Criteria

Age Range: 18 years to 65 years

Inclusion Criteria: * Age: Male and female participants of African descent (including, but not limited to, Black, Black African, Black Caribbean, African American, Afro-Caribbean, Afro-Latino, West African, Mixed Black backgrounds, or other self-identified African diaspora heritage) aged 18 to 70 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, except participants with bundle branch block who should excluded if QTcF\> 480 ms. * Acute coronary syndrome/Acute myocardial infraction with or without any coronary intervention within 6 months. * Transient ischaemic attack/ stroke within 3 months. * High grade (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 past use of insulin for more than 3 months and/or any maintenance therapy with insulin within 2 months of screening. 2. Screening Haemoglobin A1c \> 8.0% 3. Receiving more than one anti-hyperglycaemic agent (excluding SGLT inhibitors and GLP-1 receptor agonists is permitted if prescribed for a purpose other than glycaemic control which can be taken in addition to one other 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. * A history of trypanosomiasis or leishmaniasis.

Interventions

COMBINATION_PRODUCT

AZD2373-Arm 1

COMBINATION_PRODUCT

AZD2373-Arm 2

COMBINATION_PRODUCT

Placebo

DEVICE

APOL1 Genotyping Clinical Trial Assay

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Conditions

APOL1-Mediated Kidney Disease

Locations

Research Site

Alabaster, Alabama 35007

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Birmingham, Alabama 35205

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Irondale, Alabama 35210

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Surprise, Arizona 85374

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Beverly Hills, California 90211

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Concord, California 94520

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Fremont, California 94538

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Gardena, California 90247

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Los Angeles, California 90095

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Valencia, California 91355

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Boca Raton, Florida 33487

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Brandon, Florida 33511

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Miami, Florida 33126

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Miami, Florida 33173

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Orlando, Florida 32808

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Pompano Beach, Florida 33060

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Atlanta, Georgia 30322

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Augusta, Georgia 30904

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Augusta, Georgia 30909

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Augusta, Georgia 30912

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Columbus, Georgia 31901

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Columbus, Georgia 31904

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Duluth, Georgia 30096

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Hinesville, Georgia 31313

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Lawrenceville, Georgia 30046

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Macon, Georgia 31210

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Macon, Georgia 31217

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Marietta, Georgia 30067

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Savannah, Georgia 31406

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Stockbridge, Georgia 30281

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Chicago, Illinois 60612

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Hinsdale, Illinois 60521

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Rockford, Illinois 61107

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Baton Rouge, Louisiana 70808

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Lafayette, Louisiana 70508

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New Orleans, Louisiana 70112

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Shreveport, Louisiana 71103

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Bethesda, Maryland 20889

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Potomac, Maryland 20854

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Boston, Massachusetts 02114

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Lansing, Michigan 48911

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Roseville, Michigan 48066

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Minneapolis, Minnesota 55455

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Tupelo, Mississippi 38801

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Brooklyn, New York 11203

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Brooklyn, New York 11221

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Laurelton, New York 11413

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New York, New York 10010

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Rockville Centre, New York 11570

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Cary, North Carolina 27511

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Durham, North Carolina 27705

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Fayetteville, North Carolina 28304

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Gastonia, North Carolina 28054

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Greenville, North Carolina 27834

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Jacksonville, North Carolina 28546

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Kinston, North Carolina 28501

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Winston-Salem, North Carolina 27103

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Winston-Salem, North Carolina 27157

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Cincinnati, Ohio 45246

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Columbus, Ohio 43210

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Butler, Pennsylvania 16001

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Exton, Pennsylvania 19341

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Philadelphia, Pennsylvania 19104

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Anderson, South Carolina 29621

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Columbia, South Carolina 29203

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Orangeburg, South Carolina 29118

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Spartanburg, South Carolina 29306

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Chattanooga, Tennessee 37404

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Nashville, Tennessee 37232

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Conroe, Texas 77384

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Dallas, Texas 75234

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Dallas, Texas 75235

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Houston, Texas 77054

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Mesquite, Texas 75149

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Pearland, Texas 77584

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San Antonio, Texas 78212

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Alexandria, Virginia 22311

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Norfolk, Virginia 23510

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Richmond, Virginia 23298

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Birmingham, B15 2WB

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Leicester, Le5 4PW

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Liverpool, L22 0LG

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London, NW3 2QG

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London, SE1 9RT

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London, SE5 8AZ

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London, SM5 1AA

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London, SW17 0QT

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London, SW7 2AZ

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Manchester, M13 9WL

United Kingdom