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[Essai de dispositif qui n'est pas approuvé ou effacé par la FDA américaine] (APPRECIATE)

9 octobre 2026 mis à jour par: AstraZeneca

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.

Aperçu de l'étude

Statut

Actif, ne recrute pas

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Réel)

63

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • Royaume-Uni
      • Birmingham, Royaume-Uni, B15 2WB
        • Research Site
      • Leicester, Royaume-Uni, Le5 4PW
        • Research Site
      • Liverpool, Royaume-Uni, L22 0LG
        • Research Site
      • London, Royaume-Uni, SE1 9RT
        • Research Site
      • London, Royaume-Uni, NW3 2QG
        • Research Site
      • London, Royaume-Uni, SW17 0QT
        • Research Site
      • London, Royaume-Uni, SE5 8AZ
        • Research Site
      • London, Royaume-Uni, SM5 1AA
        • Research Site
      • London, Royaume-Uni, SW7 2AZ
        • Research Site
      • Manchester, Royaume-Uni, M13 9WL
        • Research Site
  • États-Unis
    • Alabama
      • Alabaster, Alabama, États-Unis, 35007
        • Research Site
      • Birmingham, Alabama, États-Unis, 35205
        • Research Site
      • Irondale, Alabama, États-Unis, 35210
        • Research Site
    • Arizona
      • Surprise, Arizona, États-Unis, 85374
        • Research Site
    • California
      • Beverly Hills, California, États-Unis, 90211
        • Research Site
      • Concord, California, États-Unis, 94520
        • Research Site
      • Fremont, California, États-Unis, 94538
        • Research Site
      • Gardena, California, États-Unis, 90247
        • Research Site
      • Los Angeles, California, États-Unis, 90095
        • Research Site
      • Valencia, California, États-Unis, 91355
        • Research Site
    • Florida
      • Boca Raton, Florida, États-Unis, 33487
        • Research Site
      • Brandon, Florida, États-Unis, 33511
        • Research Site
      • Miami, Florida, États-Unis, 33126
        • Research Site
      • Miami, Florida, États-Unis, 33173
        • Research Site
      • Orlando, Florida, États-Unis, 32808
        • Research Site
      • Pompano Beach, Florida, États-Unis, 33060
        • Research Site
    • Georgia
      • Atlanta, Georgia, États-Unis, 30322
        • Research Site
      • Augusta, Georgia, États-Unis, 30912
        • Research Site
      • Augusta, Georgia, États-Unis, 30909
        • Research Site
      • Augusta, Georgia, États-Unis, 30904
        • Research Site
      • Columbus, Georgia, États-Unis, 31904
        • Research Site
      • Columbus, Georgia, États-Unis, 31901
        • Research Site
      • Duluth, Georgia, États-Unis, 30096
        • Research Site
      • Hinesville, Georgia, États-Unis, 31313
        • Research Site
      • Lawrenceville, Georgia, États-Unis, 30046
        • Research Site
      • Macon, Georgia, États-Unis, 31217
        • Research Site
      • Macon, Georgia, États-Unis, 31210
        • Research Site
      • Marietta, Georgia, États-Unis, 30067
        • Research Site
      • Savannah, Georgia, États-Unis, 31406
        • Research Site
      • Stockbridge, Georgia, États-Unis, 30281
        • Research Site
    • Illinois
      • Chicago, Illinois, États-Unis, 60612
        • Research Site
      • Chicago, Illinois, États-Unis, 60643
        • Research Site
      • Hinsdale, Illinois, États-Unis, 60521
        • Research Site
      • Rockford, Illinois, États-Unis, 61107
        • Research Site
    • Louisiana
      • Baton Rouge, Louisiana, États-Unis, 70808
        • Research Site
      • Lafayette, Louisiana, États-Unis, 70508
        • Research Site
      • New Orleans, Louisiana, États-Unis, 70112
        • Research Site
      • Shreveport, Louisiana, États-Unis, 71103
        • Research Site
    • Maryland
      • Bethesda, Maryland, États-Unis, 20889
        • Research Site
      • Potomac, Maryland, États-Unis, 20854
        • Research Site
    • Massachusetts
      • Boston, Massachusetts, États-Unis, 02114
        • Research Site
      • Worcester, Massachusetts, États-Unis, 01608
        • Research Site
    • Michigan
      • Lansing, Michigan, États-Unis, 48911
        • Research Site
      • Roseville, Michigan, États-Unis, 48066
        • Research Site
    • Minnesota
      • Minneapolis, Minnesota, États-Unis, 55455
        • Research Site
    • Mississippi
      • Columbus, Mississippi, États-Unis, 39705
        • Research Site
      • Tupelo, Mississippi, États-Unis, 38801
        • Research Site
    • New York
      • Brooklyn, New York, États-Unis, 11203
        • Research Site
      • Brooklyn, New York, États-Unis, 11221
        • Research Site
      • Laurelton, New York, États-Unis, 11413
        • Research Site
      • New York, New York, États-Unis, 10010
        • Research Site
      • Rockville Centre, New York, États-Unis, 11570
        • Research Site
      • The Bronx, New York, États-Unis, 10461
        • Research Site
    • North Carolina
      • Cary, North Carolina, États-Unis, 27511
        • Research Site
      • Durham, North Carolina, États-Unis, 27705
        • Research Site
      • Fayetteville, North Carolina, États-Unis, 28304
        • Research Site
      • Gastonia, North Carolina, États-Unis, 28054
        • Research Site
      • Greenville, North Carolina, États-Unis, 27834
        • Research Site
      • Jacksonville, North Carolina, États-Unis, 28546
        • Research Site
      • Kinston, North Carolina, États-Unis, 28501
        • Research Site
      • Winston-Salem, North Carolina, États-Unis, 27103
        • Research Site
      • Winston-Salem, North Carolina, États-Unis, 27157
        • Research Site
    • Ohio
      • Cincinnati, Ohio, États-Unis, 45246
        • Research Site
      • Columbus, Ohio, États-Unis, 43210
        • Research Site
    • Pennsylvania
      • Bridgeville, Pennsylvania, États-Unis, 15017
        • Research Site
      • Butler, Pennsylvania, États-Unis, 16001
        • Research Site
      • Exton, Pennsylvania, États-Unis, 19341
        • Research Site
      • Philadelphia, Pennsylvania, États-Unis, 19104
        • Research Site
    • South Carolina
      • Anderson, South Carolina, États-Unis, 29621
        • Research Site
      • Columbia, South Carolina, États-Unis, 29203
        • Research Site
      • Orangeburg, South Carolina, États-Unis, 29118
        • Research Site
      • Spartanburg, South Carolina, États-Unis, 29306
        • Research Site
    • Tennessee
      • Chattanooga, Tennessee, États-Unis, 37404
        • Research Site
      • Nashville, Tennessee, États-Unis, 37232
        • Research Site
    • Texas
      • Conroe, Texas, États-Unis, 77304
        • Research Site
      • Conroe, Texas, États-Unis, 77384
        • Research Site
      • Dallas, Texas, États-Unis, 75234
        • Research Site
      • Dallas, Texas, États-Unis, 75235
        • Research Site
      • Houston, Texas, États-Unis, 77054
        • Research Site
      • Katy, Texas, États-Unis, 77450
        • Research Site
      • Mesquite, Texas, États-Unis, 75149
        • Research Site
      • Pearland, Texas, États-Unis, 77584
        • Research Site
      • San Antonio, Texas, États-Unis, 78212
        • Research Site
    • Virginia
      • Norfolk, Virginia, États-Unis, 23510
        • Research Site
      • Portsmouth, Virginia, États-Unis, 23708
        • Research Site
      • Richmond, Virginia, États-Unis, 23298
        • Research Site

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 65 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Quadruple

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Comparateur placebo: Part A - 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.
Produit combiné: Placebo

Accessorized Pre-Filled Syringe (Solution for injection).

Dispositif: 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.
Expérimental: Part A - 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.
Dispositif: 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.

Produit combiné: AZD2373-Arm 1

Accessorized Pre-Filled Syringe (Solution for injection)
Expérimental: Part A - 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.
Dispositif: 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.

Produit combiné: AZD2373-Arm 2

Accessorized Pre-Filled Syringe (Solution for injection)
Expérimental: Part B - AZD2373 Arm 1

Participants will be randomized at a 4:1 ratio to 2 study treatment arms. Participants will receive SC injection of the assigned dose
Dispositif: 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.

Produit combiné: AZD2373-Arm 2

Accessorized Pre-Filled Syringe (Solution for injection)
Comparateur placebo: Part B - Placebo group

Participants will be randomized at a 4:1 ratio to 2 study treatment arms. Participants will receive SC injection of the assigned dose
Produit combiné: Placebo

Accessorized Pre-Filled Syringe (Solution for injection).

Dispositif: 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.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Relative change in Urine Albumin-Creatinine Ratio (UACR)
Délai: From Baseline at Week 30

To assess the effect of AZD2373 versus placebo in reducing albuminuria
From Baseline at Week 30

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Relative change in Urine Albumin-Creatinine Ratio (UACR)
Délai: From Baseline at the End of Treatment (Until the last participant completes Week 30)

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)
Délai: From Baseline at Week 30

To assess the effect of AZD2373 versus placebo in reducing proteinuria
From Baseline at Week 30
Relative change in Urine Protein-Creatinine Ratio (UPCR)
Délai: From Baseline at the End of Treatment (Until the last participant completes Week 30)

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)
Délai: From Baseline at Week 30

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)
Délai: From Baseline at the End of Treatment (Until the last participant completes Week 30)

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)
eGFR slope
Délai: From Baseline at the End of Treatment (Until the last participant completes Week 30)

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)
Délai: During treatment (up to Week 30) and follow-up (up to 12 weeks)

To evaluate the immunogenicity of AZD2373
During treatment (up to Week 30) and follow-up (up to 12 weeks)
Plasma concentration
Délai: From Baseline at the End of Treatment (Until the last participant completes Week 30)

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).
Délai: From baseline at the End of Treatment (Until the last participant completes Week 30)

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)

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

AstraZeneca

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

5 mars 2025

Achèvement primaire (Estimé)

4 octobre 2027

Achèvement de l'étude (Estimé)

4 octobre 2027

Dates d'inscription aux études

Première soumission

24 janvier 2025

Première soumission répondant aux critères de contrôle qualité

7 février 2025

Première publication (Réel)

13 février 2025

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

13 octobre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

9 octobre 2026

Dernière vérification

1 octobre 2026

Plus d'information

Termes liés à cette étude

Mots clés

Autres numéros d'identification d'étude

  • D6800C00005

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

OUI

Description du régime IPD

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.

Délai de partage IPD

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.

Critères d'accès au partage IPD

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.

Type d'informations de prise en charge du partage d'IPD

  • PROTOCOLE D'ÉTUDE
  • SÈVE

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Oui

Étudie un produit d'appareil réglementé par la FDA américaine

Oui

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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