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

Study identifier:D6800C00005

ClinicalTrials.gov identifier:NCT06824987

EudraCT identifier:N/A

CTIS identifier:N/A

Recruiting

Official Title

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)

Medical condition

APOL1-Mediated Kidney Disease

Phase

Phase 2

Healthy volunteers

Study drug

AZD2373-Arm 1, AZD2373-Arm 2, Placebo

Sex

All

Estimated Enrollment

Study type

Interventional

Age

18 Years - 65 Years

Date

Study Start Date: 05 Mar 2025

Estimated Primary Completion Date: 30 Aug 2027

Estimated Study Completion Date: 30 Aug 2027

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Mar 2025 by AstraZeneca

Collaborators

Inclusion and exclusion 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:
a) Current or any past use of insulin
b) Screening Haemoglobin A1c > 8.0%
c) 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.

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Arms	Assigned Interventions
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). Other Name: Not applicable 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. Other Name: Not applicable
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.	Combination Product: AZD2373-Arm 1 Accessorized Pre-Filled Syringe (Solution for injection) Other Name: Not applicable 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. Other Name: Not applicable
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.	Combination Product: AZD2373-Arm 2 Accessorized Pre-Filled Syringe (Solution for injection) Other Name: Not applicable 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. Other Name: Not applicable

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]