[Proces urządzenia, który nie jest zatwierdzony ani oczyszczony przez FDA USA] (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.
Przegląd badań
Status
Szczegółowy opis
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.
Typ studiów
Zapisy (Rzeczywisty)
Faza
- Faza 2
Kontakty i lokalizacje
Lokalizacje studiów
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Alabama
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Alabaster, Alabama, Stany Zjednoczone, 35007
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Birmingham, Alabama, Stany Zjednoczone, 35205
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Irondale, Alabama, Stany Zjednoczone, 35210
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Arizona
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Surprise, Arizona, Stany Zjednoczone, 85374
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California
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Beverly Hills, California, Stany Zjednoczone, 90211
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Concord, California, Stany Zjednoczone, 94520
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Fremont, California, Stany Zjednoczone, 94538
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Gardena, California, Stany Zjednoczone, 90247
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Los Angeles, California, Stany Zjednoczone, 90095
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Valencia, California, Stany Zjednoczone, 91355
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Florida
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Boca Raton, Florida, Stany Zjednoczone, 33487
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Brandon, Florida, Stany Zjednoczone, 33511
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Miami, Florida, Stany Zjednoczone, 33126
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Miami, Florida, Stany Zjednoczone, 33173
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Orlando, Florida, Stany Zjednoczone, 32808
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Pompano Beach, Florida, Stany Zjednoczone, 33060
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Georgia
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Atlanta, Georgia, Stany Zjednoczone, 30322
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Augusta, Georgia, Stany Zjednoczone, 30912
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Augusta, Georgia, Stany Zjednoczone, 30909
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Augusta, Georgia, Stany Zjednoczone, 30904
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Columbus, Georgia, Stany Zjednoczone, 31904
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Columbus, Georgia, Stany Zjednoczone, 31901
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Duluth, Georgia, Stany Zjednoczone, 30096
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Hinesville, Georgia, Stany Zjednoczone, 31313
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Lawrenceville, Georgia, Stany Zjednoczone, 30046
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Macon, Georgia, Stany Zjednoczone, 31217
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Macon, Georgia, Stany Zjednoczone, 31210
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Marietta, Georgia, Stany Zjednoczone, 30067
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Savannah, Georgia, Stany Zjednoczone, 31406
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Stockbridge, Georgia, Stany Zjednoczone, 30281
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Illinois
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Chicago, Illinois, Stany Zjednoczone, 60612
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Chicago, Illinois, Stany Zjednoczone, 60643
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Hinsdale, Illinois, Stany Zjednoczone, 60521
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Rockford, Illinois, Stany Zjednoczone, 61107
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Louisiana
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Baton Rouge, Louisiana, Stany Zjednoczone, 70808
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Lafayette, Louisiana, Stany Zjednoczone, 70508
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New Orleans, Louisiana, Stany Zjednoczone, 70112
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Shreveport, Louisiana, Stany Zjednoczone, 71103
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Maryland
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Bethesda, Maryland, Stany Zjednoczone, 20889
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Potomac, Maryland, Stany Zjednoczone, 20854
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Massachusetts
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Boston, Massachusetts, Stany Zjednoczone, 02114
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Worcester, Massachusetts, Stany Zjednoczone, 01608
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Michigan
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Lansing, Michigan, Stany Zjednoczone, 48911
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Roseville, Michigan, Stany Zjednoczone, 48066
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Minnesota
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Minneapolis, Minnesota, Stany Zjednoczone, 55455
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Mississippi
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Columbus, Mississippi, Stany Zjednoczone, 39705
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Tupelo, Mississippi, Stany Zjednoczone, 38801
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New York
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Brooklyn, New York, Stany Zjednoczone, 11203
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Brooklyn, New York, Stany Zjednoczone, 11221
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Laurelton, New York, Stany Zjednoczone, 11413
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New York, New York, Stany Zjednoczone, 10010
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Rockville Centre, New York, Stany Zjednoczone, 11570
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The Bronx, New York, Stany Zjednoczone, 10461
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North Carolina
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Cary, North Carolina, Stany Zjednoczone, 27511
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Durham, North Carolina, Stany Zjednoczone, 27705
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Fayetteville, North Carolina, Stany Zjednoczone, 28304
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Gastonia, North Carolina, Stany Zjednoczone, 28054
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Greenville, North Carolina, Stany Zjednoczone, 27834
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Jacksonville, North Carolina, Stany Zjednoczone, 28546
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Kinston, North Carolina, Stany Zjednoczone, 28501
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Winston-Salem, North Carolina, Stany Zjednoczone, 27103
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Winston-Salem, North Carolina, Stany Zjednoczone, 27157
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Ohio
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Cincinnati, Ohio, Stany Zjednoczone, 45246
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Columbus, Ohio, Stany Zjednoczone, 43210
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Pennsylvania
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Bridgeville, Pennsylvania, Stany Zjednoczone, 15017
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Butler, Pennsylvania, Stany Zjednoczone, 16001
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Exton, Pennsylvania, Stany Zjednoczone, 19341
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Philadelphia, Pennsylvania, Stany Zjednoczone, 19104
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South Carolina
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Anderson, South Carolina, Stany Zjednoczone, 29621
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Columbia, South Carolina, Stany Zjednoczone, 29203
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Orangeburg, South Carolina, Stany Zjednoczone, 29118
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Spartanburg, South Carolina, Stany Zjednoczone, 29306
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Tennessee
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Chattanooga, Tennessee, Stany Zjednoczone, 37404
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Nashville, Tennessee, Stany Zjednoczone, 37232
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Texas
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Conroe, Texas, Stany Zjednoczone, 77304
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Conroe, Texas, Stany Zjednoczone, 77384
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Dallas, Texas, Stany Zjednoczone, 75234
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Dallas, Texas, Stany Zjednoczone, 75235
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Houston, Texas, Stany Zjednoczone, 77054
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Katy, Texas, Stany Zjednoczone, 77450
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Mesquite, Texas, Stany Zjednoczone, 75149
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Pearland, Texas, Stany Zjednoczone, 77584
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San Antonio, Texas, Stany Zjednoczone, 78212
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Virginia
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Norfolk, Virginia, Stany Zjednoczone, 23510
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Portsmouth, Virginia, Stany Zjednoczone, 23708
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Richmond, Virginia, Stany Zjednoczone, 23298
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Birmingham, Zjednoczone Królestwo, B15 2WB
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Leicester, Zjednoczone Królestwo, Le5 4PW
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Liverpool, Zjednoczone Królestwo, L22 0LG
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London, Zjednoczone Królestwo, SE1 9RT
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London, Zjednoczone Królestwo, NW3 2QG
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London, Zjednoczone Królestwo, SW17 0QT
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London, Zjednoczone Królestwo, SE5 8AZ
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London, Zjednoczone Królestwo, SM5 1AA
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London, Zjednoczone Królestwo, SW7 2AZ
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Manchester, Zjednoczone Królestwo, M13 9WL
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Kryteria uczestnictwa
Kryteria kwalifikacji
Wiek uprawniający do nauki
Akceptuje zdrowych ochotników
Płeć kwalifikująca się do nauki
Opis
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:
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Participants with diagnosis of Type 1 diabetes mellitus.
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Body Mass Index > 45 kg/m2.
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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).
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QTcF > 470 ms, except participants with bundle branch block who should excluded if QTcF> 480 ms.
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Acute coronary syndrome/Acute myocardial infraction with or without any coronary intervention within 6 months.
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Transient ischaemic attack/ stroke within 3 months.
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High grade (second to third) degree AV block or clinically significant sinus node dysfunction untreated with pacemaker.
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A history of ventricular arrhythmias requiring treatment.
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Participants with Type 2 diabetes mellitus must be excluded if ANY of the following conditions are present:
- Current or past use of insulin for more than 3 months and/or any maintenance therapy with insulin within 2 months of screening.
- Screening Haemoglobin A1c > 8.0%
- 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).
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Participant on kidney replacement therapy (dialysis or kidney transplant) or any other organ transplant.
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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.
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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.
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History of a diagnosed coagulopathy, a major unexplained bleeding event, or other high-risk bleeding diathesis.
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A history of trypanosomiasis or leishmaniasis.
Plan studiów
Jak projektuje się badanie?
Szczegóły projektu
- Główny cel: Leczenie
- Przydział: Randomizowane
- Model interwencyjny: Przydział równoległy
- Maskowanie: Poczwórny
Broń i interwencje
Grupa uczestników / Arm |
Interwencja / Leczenie |
|---|---|
|
Komparator 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. |
Accessorized Pre-Filled Syringe (Solution for injection). 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. |
|
Eksperymentalny: 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. |
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. Accessorized Pre-Filled Syringe (Solution for injection) |
|
Eksperymentalny: 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. |
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. Accessorized Pre-Filled Syringe (Solution for injection) |
|
Eksperymentalny: 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 |
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. Accessorized Pre-Filled Syringe (Solution for injection) |
|
Komparator 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 |
Accessorized Pre-Filled Syringe (Solution for injection). 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. |
Co mierzy badanie?
Podstawowe miary wyniku
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
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Relative change in Urine Albumin-Creatinine Ratio (UACR)
Ramy czasowe: From Baseline at Week 30
|
To assess the effect of AZD2373 versus placebo in reducing albuminuria |
From Baseline at Week 30
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Miary wyników drugorzędnych
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
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Relative change in Urine Albumin-Creatinine Ratio (UACR)
Ramy czasowe: From Baseline at the End of Treatment (Until the last participant completes Week 30)
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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)
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Relative change in Urine Protein-Creatinine Ratio (UPCR)
Ramy czasowe: From Baseline at Week 30
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To assess the effect of AZD2373 versus placebo in reducing proteinuria |
From Baseline at Week 30
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Relative change in Urine Protein-Creatinine Ratio (UPCR)
Ramy czasowe: From Baseline at the End of Treatment (Until the last participant completes Week 30)
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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)
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Proportion of participants achieving a 45% or greater reduction in Urine Albumin-Creatinine Ratio (UACR)
Ramy czasowe: From Baseline at Week 30
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To assess the proportion of participants achieving a 45% or greater Urine Albumin-Creatinine Ratio (UACR) reduction by treatment |
From Baseline at Week 30
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Proportion of participants achieving a 45% or greater reduction in Urine Albumin-Creatinine Ratio (UACR)
Ramy czasowe: 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)
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eGFR slope
Ramy czasowe: From Baseline at the End of Treatment (Until the last participant completes Week 30)
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To assess pooled AZD2373 doses versus placebo on eGFR change |
From Baseline at the End of Treatment (Until the last participant completes Week 30)
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Incidence of development of ADA and ADA titer (if participants are ADA-positive)
Ramy czasowe: 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)
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Plasma concentration
Ramy czasowe: 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)
|
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Adverse Events (AEs), Serious Adverse Events (SAEs), and Drug Adverse Events (DAEs).
Ramy czasowe: 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)
|
Współpracownicy i badacze
Sponsor
Daty zapisu na studia
Główne daty studiów
Rozpoczęcie studiów (Rzeczywisty)
Zakończenie podstawowe (Szacowany)
Ukończenie studiów (Szacowany)
Daty rejestracji na studia
Pierwszy przesłany
Pierwszy przesłany, który spełnia kryteria kontroli jakości
Pierwszy wysłany (Rzeczywisty)
Aktualizacje rekordów badań
Ostatnia wysłana aktualizacja (Rzeczywisty)
Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości
Ostatnia weryfikacja
Więcej informacji
Terminy związane z tym badaniem
Słowa kluczowe
Inne numery identyfikacyjne badania
- D6800C00005
Plan dla danych uczestnika indywidualnego (IPD)
Planujesz udostępniać dane poszczególnych uczestników (IPD)?
Opis planu 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.
Ramy czasowe udostępniania 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.
Kryteria dostępu do udostępniania 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.
Typ informacji pomocniczych dotyczących udostępniania IPD
- PROTOKÓŁ BADANIA
- SOK ROŚLINNY
Informacje o lekach i urządzeniach, dokumenty badawcze
Bada produkt leczniczy regulowany przez amerykańską FDA
Bada produkt urządzenia regulowany przez amerykańską FDA
Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .