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

Phase 2b Multicentre, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Dose-Ranging Study to Assess the Efficacy, Safety, and Tolerability of AZD2373 in Participants With APOL1-Mediated Kidney Disease (APPRECIATE)

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.

Study Overview

• Status: Recruiting
• Conditions: APOL1-Mediated Kidney Disease
• Intervention / Treatment: Combination product: Placebo; Device: APOL1 Genotyping Clinical Trial Assay; Combination product: AZD2373-Arm 1; Combination product: AZD2373-Arm 2

Detailed Description

This is a Phase 2b study to assess efficacy and safety of AZD2373 involving 3 study treatment arms 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.

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.

Approximately 96 participants will be randomized to study intervention (approximately 32 participants in each treatment group).

• Study Type: Interventional
• Enrollment (Estimated): 96
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• United Kingdom
  • Birmingham, United Kingdom, B15 2WB
    • Not yet recruiting
    • Research Site
  • Leicester, United Kingdom, LE5 4PW
    • Not yet recruiting
    • Research Site
  • Liverpool, United Kingdom, L22 0LG
    • Not yet recruiting
    • Research Site
  • London, United Kingdom, NW3 2QG
    • Not yet recruiting
    • Research Site
  • London, United Kingdom, SE1 9RT
    • Not yet recruiting
    • Research Site
  • London, United Kingdom, SW17 0QT
    • Not yet recruiting
    • Research Site
  • London, United Kingdom, SM5 1AA
    • Not yet recruiting
    • Research Site
  • London, United Kingdom, SE5 8AZ
    • Not yet recruiting
    • Research Site
  • London, United Kingdom, SW7 2AZ
    • Not yet recruiting
    • Research Site
  • Manchester, United Kingdom, M13 9WL
    • Not yet recruiting
    • Research Site
• United States
  • Alabama
    • Alabaster, Alabama, United States, 35007
      • Recruiting
      • Research Site
    • Birmingham, Alabama, United States, 35205
      • Recruiting
      • Research Site
    • Irondale, Alabama, United States, 35210
      • Recruiting
      • Research Site
  • California
    • Beverly Hills, California, United States, 90211
      • Recruiting
      • Research Site
    • Gardena, California, United States, 90247
      • Recruiting
      • Research Site
    • Los Angeles, California, United States, 90095
      • Not yet recruiting
      • Research Site
    • Valencia, California, United States, 91355
      • Recruiting
      • Research Site
  • Florida
    • Brandon, Florida, United States, 33511
      • Recruiting
      • Research Site
    • Miami, Florida, United States, 33173
      • Recruiting
      • Research Site
    • Miami, Florida, United States, 33126
      • Recruiting
      • Research Site
    • Orlando, Florida, United States, 32808
      • Recruiting
      • Research Site
    • Pompano Beach, Florida, United States, 33060
      • Recruiting
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Not yet recruiting
      • Research Site
    • Augusta, Georgia, United States, 30912
      • Not yet recruiting
      • Research Site
    • Augusta, Georgia, United States, 30909
      • Recruiting
      • Research Site
    • Columbus, Georgia, United States, 31904
      • Recruiting
      • Research Site
    • Columbus, Georgia, United States, 31901
      • Recruiting
      • Research Site
    • Duluth, Georgia, United States, 30096
      • Recruiting
      • Research Site
    • Hinesville, Georgia, United States, 31313
      • Recruiting
      • Research Site
    • Lawrenceville, Georgia, United States, 30046
      • Recruiting
      • Research Site
    • Macon, Georgia, United States, 31217
      • Recruiting
      • Research Site
    • Macon, Georgia, United States, 31210
      • Recruiting
      • Research Site
    • Marietta, Georgia, United States, 30067
      • Recruiting
      • Research Site
    • Savannah, Georgia, United States, 31406
      • Recruiting
      • Research Site
    • Stockbridge, Georgia, United States, 30281
      • Recruiting
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Not yet recruiting
      • Research Site
    • Hinsdale, Illinois, United States, 60521
      • Recruiting
      • Research Site
  • Louisiana
    • Lafayette, Louisiana, United States, 70508
      • Recruiting
      • Research Site
    • New Orleans, Louisiana, United States, 70112
      • Recruiting
      • Research Site
  • Maryland
    • Bethesda, Maryland, United States, 20889
      • Recruiting
      • Research Site
    • Potomac, Maryland, United States, 20854
      • Recruiting
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Not yet recruiting
      • Research Site
  • Michigan
    • Roseville, Michigan, United States, 48066
      • Recruiting
      • Research Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Not yet recruiting
      • Research Site
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • Recruiting
      • Research Site
  • New York
    • Brooklyn, New York, United States, 11203
      • Recruiting
      • Research Site
    • Brooklyn, New York, United States, 11221
      • Recruiting
      • Research Site
    • Laurelton, New York, United States, 11413
      • Recruiting
      • Research Site
    • New York, New York, United States, 10010
      • Not yet recruiting
      • Research Site
  • North Carolina
    • Cary, North Carolina, United States, 27511
      • Recruiting
      • Research Site
    • Durham, North Carolina, United States, 27705
      • Not yet recruiting
      • Research Site
    • Fayetteville, North Carolina, United States, 28304
      • Recruiting
      • Research Site
    • Gastonia, North Carolina, United States, 28054
      • Recruiting
      • Research Site
    • Greenville, North Carolina, United States, 27834
      • Recruiting
      • Research Site
    • Jacksonville, North Carolina, United States, 28546
      • Recruiting
      • Research Site
    • Kinston, North Carolina, United States, 28501
      • Recruiting
      • Research Site
    • Winston-Salem, North Carolina, United States, 27103
      • Recruiting
      • Research Site
    • Winston-Salem, North Carolina, United States, 27157
      • Recruiting
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45246
      • Recruiting
      • Research Site
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Not yet recruiting
      • Research Site
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Recruiting
      • Research Site
    • Columbia, South Carolina, United States, 29203
      • Recruiting
      • Research Site
    • Orangeburg, South Carolina, United States, 29118
      • Recruiting
      • Research Site
    • Spartanburg, South Carolina, United States, 29306
      • Recruiting
      • Research Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Not yet recruiting
      • Research Site
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Research Site
  • Texas
    • Conroe, Texas, United States, 77384
      • Not yet recruiting
      • Research Site
    • Dallas, Texas, United States, 75235
      • Recruiting
      • Research Site
    • Dallas, Texas, United States, 75234
      • Recruiting
      • Research Site
    • Houston, Texas, United States, 77054
      • Recruiting
      • Research Site
    • Mesquite, Texas, United States, 75149
      • Recruiting
      • Research Site
    • Pearland, Texas, United States, 77584
      • Recruiting
      • Research Site
    • San Antonio, Texas, United States, 78212
      • Recruiting
      • Research Site
  • Virginia
    • Alexandria, Virginia, United States, 22311
      • Withdrawn
      • Research Site
    • Norfolk, Virginia, United States, 23510
      • Not yet recruiting
      • Research Site
    • Richmond, Virginia, United States, 23298
      • Not yet recruiting
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo group; Participants will be randomized at a 1:1:1 ratio to 3 study treatment arms. Participants will receive SC injection of the assigned dose.	Combination product: Placebo; Accessorized Pre-Filled Syringe (Solution for injection).; Device: APOL1 Genotyping Clinical Trial Assay; The APOL1 Genotyping Clinical Trial Assay, an investigational use only qualitative Polymerase Chain Reaction invitro diagnostic assay, discriminates between the rs73885319 G1(S342G) and rs71785313 G2 genotypes within the APOL1 gene from DNA extracted from whole blood.
Experimental: AZD2373 - Arm 1; Participants will be randomized at a 1:1:1 ratio to 3 study treatment arms. Participants will receive SC injection of the assigned dose.	Device: APOL1 Genotyping Clinical Trial Assay; The APOL1 Genotyping Clinical Trial Assay, an investigational use only qualitative Polymerase Chain Reaction invitro diagnostic assay, discriminates between the rs73885319 G1(S342G) and rs71785313 G2 genotypes within the APOL1 gene from DNA extracted from whole blood.; Combination product: AZD2373-Arm 1; Accessorized Pre-Filled Syringe (Solution for injection)
Experimental: AZD2373 - Arm 2; Participants will be randomized at a 1:1:1 ratio to 3 study treatment arms. Participants will receive SC injection of the assigned dose.	Device: APOL1 Genotyping Clinical Trial Assay; The APOL1 Genotyping Clinical Trial Assay, an investigational use only qualitative Polymerase Chain Reaction invitro diagnostic assay, discriminates between the rs73885319 G1(S342G) and rs71785313 G2 genotypes within the APOL1 gene from DNA extracted from whole blood.; Combination product: AZD2373-Arm 2; Accessorized Pre-Filled Syringe (Solution for injection)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative change in Urine Albumin-Creatinine Ratio (UACR)	To assess the effect of AZD2373 versus placebo in reducing albuminuria	From Baseline at Week 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative change in Urine Albumin-Creatinine Ratio (UACR)	To assess the effect of AZD2373 versus placebo in reducing albuminuria	From Baseline at the End of Treatment (Until the last participant completes Week 30)
Relative change in Urine Protein-Creatinine Ratio (UPCR)	To assess the effect of AZD2373 versus placebo in reducing proteinuria	From Baseline at Week 30
Relative change in Urine Protein-Creatinine Ratio (UPCR)	To assess the effect of AZD2373 versus placebo in reducing proteinuria	From Baseline at the End of Treatment (Until the last participant completes Week 30)
Proportion of participants achieving a 45% or greater reduction in Urine Albumin-Creatinine Ratio (UACR)	To assess the proportion of participants achieving a 45% or greater Urine Albumin-Creatinine Ratio (UACR) reduction by treatment	From Baseline at Week 30
Proportion of participants achieving a 45% or greater reduction in Urine Albumin-Creatinine Ratio (UACR)	To assess the proportion of participants achieving a 45% or greater Urine Albumin-Creatinine Ratio (UACR) reduction by treatment	From Baseline at the End of Treatment (Until the last participant completes Week 30)
Relative change in eGFR	To assess pooled AZD2373 doses versus placebo on eGFR change	From Baseline at the End of Treatment (Until the last participant completes Week 30)
Incidence of development of ADA and ADA titer (if participants are ADA-positive)	To evaluate the immunogenicity of AZD2373	During treatment (up to Week 30) and follow-up (up to 12 weeks)
Plasma concentration	To evaluate the PK of AZD2373	From Baseline at the End of Treatment (Until the last participant completes Week 30)
Adverse Events (AEs), Serious Adverse Events (SAEs), and Drug Adverse Events (DAEs).	To assess the safety and tolerability of ranging doses of AZD2373. These events will be collected according to the timepoints specified in the schedule of assessments, starting from the time of signing the Informed Consent Form (ICF).	From baseline at the End of Treatment (Until the last participant completes Week 30)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: James Tumlin, MD, Georgia Nephrology Research Institute; Principal Investigator: Barry Freedman, MD, Wake Forest University Health Sciences; Principal Investigator: Robert Nee, MD, Walter Reed National Military Medical Center; Principal Investigator: Asha Bailey, MD, Columbia Nephrology Associates; Principal Investigator: Claude Galphin, MD, Nephrology Associates - Main Office; Principal Investigator: Nicholas McLean, MD, Nephrology Associates, PLLC; Principal Investigator: Suneel Udani, MD, Nephrology Associates of Northern Illinois and Indiana (NANI) - Hinsdale; Principal Investigator: Thomas Wooldridge, MD, Nephrology & Hypertension Associates Ltd - Tupelo; Principal Investigator: Barry Gorlitsky, MD, Carolina Nephrology, PA - Kidney Wellness Center; Principal Investigator: Joshua Barzilay, MD, Kaiser Permanente Gwinnett Comprehensive Medical Center; Principal Investigator: Thomas Wade, MD, Emvenio Alabama; Principal Investigator: Christoper Provenzano, MD, St. Clair Nephrology; Principal Investigator: Harini Bejjanki, MD, Renal Research of Montgomery County; Principal Investigator: Mark Leibowitz, MD, Velocity Clinical Research, Gardena; Principal Investigator: Jason Eckel, MD, North Carolina Nephrology P.A. - Cary Office; Principal Investigator: Kwabena Ayesu, MD, Omega Research Group, LLC - Orlando; Principal Investigator: Koithara George Thomas, MD, Southeastern Nephrology Associates (SENA) PLLC - Jacksonville; Principal Investigator: David DeAtkine, MD, Flourish Research - Birmingham; Principal Investigator: Subbaraju Budharaju, MD, Emvenio Texas; Principal Investigator: Habib Chotani, MD, CN Internal Medicine; Principal Investigator: Pedro Hernandez, MD, Floridian Clinical Research, LLC - Miami Lakes; Principal Investigator: Aldo Heriberto Martinez Fleites, MD, Blessed Health Care & Research; Principal Investigator: Phillip Madonia, MD, Alabama Kidney Research; Principal Investigator: Carlos Martínez, MD, Renal Physicians of Georgia, P.C.; Principal Investigator: Mansi Mehta, MD, VA NY Harbor Healthcare System

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2025
• Primary Completion (Estimated): August 30, 2027
• Study Completion (Estimated): August 30, 2027

Study Registration Dates

• First Submitted: January 24, 2025
• First Submitted That Met QC Criteria: February 7, 2025
• First Posted (Actual): February 13, 2025

Study Record Updates

• Last Update Posted (Estimated): October 29, 2025
• Last Update Submitted That Met QC Criteria: October 28, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: AZD2373; APOL1-Mediated Kidney Disease
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Kidney Diseases; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: D6800C00005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org.

Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes