Denne side blev automatisk oversat, og nøjagtigheden af ​​oversættelsen er ikke garanteret. Der henvises til engelsk version for en kildetekst.

INCB000928 Indgivet som monoterapi eller i kombination med Ruxolitinib hos deltagere med anæmi på grund af myeloproliferative lidelser (LIMBER)

12. maj 2026 opdateret af: Incyte Corporation

En fase 1/2 open-label, multicenter undersøgelse af INCB000928 administreret som monoterapi eller i kombination med ruxolitinib hos deltagere med anæmi på grund af myeloproliferative lidelser

Denne fase 1/2, åbne, dosisfindende undersøgelse er beregnet til at evaluere sikkerheden og tolerabiliteten, PK, PD og effektiviteten af ​​INCB000928 administreret som monoterapi eller i kombination med ruxolitinib hos deltagere med MF, som er transfusionsafhængige eller præsenterende med symptomatisk anæmi. Denne undersøgelse vil bestå af 2 dele: dosiseskalering og udvidelse.

Studieoversigt

Status

Aktiv, ikke rekrutterende

Betingelser

Intervention / Behandling

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

84

Fase

  • Fase 2
  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Cancer Center
    • Quebec
      • Montreal, Quebec, Canada, H3T1E2
        • McGill University Jewish General Hospital
  • Det Forenede Kongerige
      • Boston, Det Forenede Kongerige, PE21 9QS
        • United Lincolnshire Hospitals
      • Lincoln, Det Forenede Kongerige, LN2 5QY
        • Lincoln County Hospital
      • Truro, Det Forenede Kongerige, TR1 3LJ
        • Royal Cornwall Hospital Truro Sunrise Centre
    • WLS
      • Cardiff, WLS, Det Forenede Kongerige, CF14 4XW
        • University Hospital of Wales
  • Forenede Stater
    • California
      • Duarte, California, Forenede Stater, 91010
        • City of Hope National Medical Center
      • Irvine, California, Forenede Stater, 92618
        • City of Hope Orange County
      • Los Angeles, California, Forenede Stater, 90089
        • USC Norris Comprehensive Cancer Center
      • Palo Alto, California, Forenede Stater, 94304
        • Stanford Cancer Center
      • San Diego, California, Forenede Stater, 92103
        • Prebys Cancer Center
    • Georgia
      • Atlanta, Georgia, Forenede Stater, 30322
        • Emory University - Winship Cancer Institute
      • Atlanta, Georgia, Forenede Stater, 30322
        • Emory University-Winship Cancer Institute
    • Michigan
      • Grand Rapids, Michigan, Forenede Stater, 49546
        • Start Midwest
    • Missouri
      • St Louis, Missouri, Forenede Stater, 63110
        • Washington University School of Medicine
    • New York
      • New York, New York, Forenede Stater, 10065
        • Weill Cornell Medical Centers
    • North Carolina
      • Durham, North Carolina, Forenede Stater, 27705
        • Duke University Medical Center, Department of Hematologic Malignancies and Cellular Therapy
    • Tennessee
      • Nashville, Tennessee, Forenede Stater, 37232
        • Vanderbilt University Medical Center
    • Texas
      • Houston, Texas, Forenede Stater, 77030
        • MD Anderson Cancer Center
  • Frankrig
      • Angers, Frankrig, 49033
        • Centre Hospitalier D'Angers
      • Marseille, Frankrig, 13273
        • Institut Paoli Calmettes
      • Paris, Frankrig, 75010
        • Hospital Saint Louis
  • Italien
      • Bergamo, Italien, 24127
        • Azienda Ospedaliera Papa Giovanni XXIII
      • Bologna, Italien, 40138
        • S Orsolas University Hospital Seragnoli Institute of Hematology
      • Florence, Italien, 50134
        • Azienda Ospedaliero-Universitaria Careggi (AOUC)
      • Orbassano, Italien, 10043
        • Azienda Ospedaliera Universitaria San Luigi Gonzaga Orbassano
      • Pavia, Italien, 27100
        • Comitato Di Bioetica Della Fondazione Irccs Policlinico San Matteo
      • Perugia, Italien, 06124
        • Ospedale Santa Maria Della Misericordia Perugia
  • Japan
      • Bunkyō City, Japan, 113-8519
        • Tokyo Medical and Dental University Hospital
      • Chiba, Japan, 260-8717
        • Chiba Cancer Center
      • Gifu, Japan, 500-8513
        • Gifu Municipal Hospital
      • Hirakata, Japan, 573-1191
        • Kansai Medical University Hospital
      • Kumamoto, Japan, 862-8655
        • Kumamoto Shinto General Hospital
      • Osaka, Japan, 541-8567
        • Osaka International Cancer Institute

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Beskrivelse

Inklusionskriterier:

  • Deltagere med MF, som er transfusionsafhængige eller til stede med symptomatisk anæmi, defineret som følger:

    1. Anæmi: En Hgb-værdi < 10 g/dL påvist under screening registreret ved 3 separate lejligheder med mindst 7 dage mellem målinger (Bemærk: RBC-transfusion skal være mindst 2 uger før Hgb-målingen under screening).
    2. Transfusionsafhængig: Deltageren har modtaget mindst 4 enheder RBC-transfusioner i løbet af de 28 dage umiddelbart forud for cyklus 1 dag 1 ELLER har i gennemsnit modtaget mindst 4 enheder RBC-transfusioner i de 8 uger umiddelbart forud for cyklus 1 dag 1, for en Hgb-niveau på < 8,5 g/dL, i fravær af blødning eller behandlingsinduceret anæmi. Derudover skal den seneste transfusionsepisode have fundet sted i de 28 dage før cyklus 1 dag 1.

  • ECOG præstationsstatusscore for følgende:

    1. 0 eller 1 for dosis-eskaleringsstadierne.
    2. 0, 1 eller 2 for dosisudvidelsesstadiet.
  • Den forventede levetid er større end 6 måneder
  • Aftale om at undgå graviditet eller far til børn.
  • Ikke berettiget til at modtage eller har ikke reageret på tilgængelige terapier for anæmi såsom ESA'er.
  • For TGA:
  • Deltagere tidligere behandlet med JAK-hæmmere i mindst 12 uger.
  • Deltagere med mellem-2 eller høj DIPSS MF i henhold til IWG-MRT kriterier.
  • For TGB:
  • Deltagerne skal have været på et terapeutisk og stabilt regime med ruxolitinib i mindst 12 på hinanden følgende uger umiddelbart forud for den første dosis af undersøgelsesbehandlingen.
  • Deltagere med mellem-1, mellem-2 eller høj DIPSS MF i henhold til IWG-MRT-kriterier.

Ekskluderingskriterier:

  • Gennemgået enhver tidligere allogen eller autolog stamcelletransplantation eller en kandidat til en sådan transplantation.
  • Enhver tidligere kemoterapi, immunmodulerende lægemiddelbehandling, immunsuppressiv terapi, biologisk terapi, endokrin terapi, målrettet terapi, antistof eller hypomethylerende middel til behandling af deltagerens sygdom, med undtagelse af ruxolitinib kun til TGB, inden for 5 halveringstider eller 28 dage (alt efter hvad der er kortere) før den første dosis af undersøgelsesbehandlingen.
  • Laboratorieværdier uden for protokoldefineret område ved screening.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomiseret
  • Interventionel model: Sekventiel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Behandlingsgruppe B (TGB)
INCB000928 vil blive administreret i kombination med ruxolitinib.
Medicin: INCB000928
INCB000928 vil blive indgivet i en protokoldefineret dosis.
Medicin: ruxolitinib
Ruxolitinib vil blive indgivet i en protokoldefineret dosis.
Eksperimentel: Behandlingsgruppe A (TGA)
INCB000928 vil blive administreret én gang dagligt (QD).
Medicin: INCB000928
INCB000928 vil blive indgivet i en protokoldefineret dosis.
Eksperimentel: Behandlingsgruppe C (TGC)
INCB000928 vil blive administreret i kombination med ruxolitinib.
Medicin: INCB000928
INCB000928 vil blive indgivet i en protokoldefineret dosis.
Medicin: ruxolitinib
Ruxolitinib vil blive indgivet i en protokoldefineret dosis.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Treatment-emergent Serious Adverse Event (SAE)
Tidsramme: up to approximately 4 years
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug/treatment. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug until 30 days after the last dose of study drug.
up to approximately 4 years
Number of Participants With Any ≥Grade 3 TEAE and Any Treatment-emergent SAE
Tidsramme: up to approximately 4 years
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug until 30 days after the last dose of study drug. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grades 1 through 5. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated. Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent treatment indicated. Grade 5: fatal.
up to approximately 4 years
Number of Participants With Dose-limiting Toxicities (DLTs)
Tidsramme: from Cycle 1 Day 1 to Cycle 1 Day 28
A DLT was defined as the occurrence of any protocol-defined toxicity occurring during the first treatment cycle, from Cycle 1 Day 1 up to and including Cycle 1 Day 28 (per regimen cycle schedule), except those with a clear alternative explanation (e.g., disease progression) or transient (≤72 hours) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination. The DLT-Evaluable Population included all non-backfill participants eligible for dose escalation who met the criteria outlined in the Analysis Population field.
from Cycle 1 Day 1 to Cycle 1 Day 28
Maximum Tolerated Dose (MTD)
Tidsramme: from Cycle 1 Day 1 to Cycle 1 Day 28
The MTD was defined as the dose at which the observed DLT rate was closest to the target DLT rate of 28% using an isotonical method that took the assumption of a monotonic dose-toxicity relationship into account. Per the protocol, the stopping rule was either (a) reaching a certain number of participants at one dose level under the early stopping rule or (b) reaching the pre-defined maximum sample size. Dose escalation was to be considered complete only when one of these conditions was met. After completion, the MTD was to be defined as the dose level closest to the target DLT rate. The MTD could not be concluded until the stopping rule was met.
from Cycle 1 Day 1 to Cycle 1 Day 28
Recommended Dose for Expansion (RDE)
Tidsramme: from Cycle 1 Day 1 to Cycle 1 Day 28
The RDE was defined as a pharmacodynamically active dose. The RDE was determined in an independent fashion by evaluation of all available data (i.e., safety, pharmacokinetic, and pharmacodynamic data) from the respective dose-escalation stage of the study for further investigation in the expansion cohort, including safety (e.g., low-grade but chronic toxicities, dose reduction, dose interruption, or missed doses of zilurgisertib and/or ruxolitinib). The RDE(s) could not exceed the MTD in each treatment group
from Cycle 1 Day 1 to Cycle 1 Day 28

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Procentvis ændring i hepcidin fra cyklus 1 dag 15 til cyklus 7 dag 1
Tidsramme: fra cyklus 1 dag 15 til cyklus 7 dag 1
Procentvis ændring blev beregnet som ([post-baseline-værdi minus basisline-værdi] / [baseline-værdi]) * 100.
fra cyklus 1 dag 15 til cyklus 7 dag 1
Percentage of Participants With Anemia Response
Tidsramme: up to Week 24
Anemia response was defined as (a) a hemoglobin (Hgb) increase of 1.5 grams per deciliter (g/dL) relative to baseline for any "rolling" 12-week period (84 days with each assessment that met this requirement) during the first 24 weeks of treatment if transfusion independent (TI) at baseline; or (b) transfusion independence for any "rolling" 12-week period (absence of any red blood cell [RBC] transfusion over any 84-day period) during the first 24 weeks of treatment if transfusion dependent (TD) at baseline.
up to Week 24
Duration of Anemia Response
Tidsramme: up to 1530 days
Duration of anemia response was defined as (a) the interval from the first onset of anemia response to the earliest date of loss of anemia response that persisted for at least 4 weeks or death from any cause (for TI participants at baseline); or (b) the duration of the RBC-TI period for participants who achieved RBC-TI for at least 12 consecutive weeks during the first 24 weeks of treatment (for TD participants at baseline).
up to 1530 days
Mean Change From Baseline in the Hgb Value Over 12-week Treatment Periods
Tidsramme: Baseline; up to 24 weeks
Mean change from baseline was assessed as the largest increase from baseline in the mean Hgb values over any rolling 12-week treatment period during the first 24 weeks of treatment. Change from baseline was calculated as the post-baseline value minus the baseline value.
Baseline; up to 24 weeks
Rate of Red Blood Cell (RBC) Transfusion From Week 24 Through Week 48
Tidsramme: from Week 24 through Week 48
The rate of RBC transfusion was defined as the average number of RBC units per participant-month during the treatment period.
from Week 24 through Week 48
Splenic Volume Response Rate at Week 24
Tidsramme: Week 24
Splenic volume response rate was defined as the percentage of participants achieving a ≥35% reduction in spleen volume at Week 24 relative to baseline as measured by magnetic resonance imaging or computed tomography scan.
Week 24
Spleen Length Response
Tidsramme: Week 24
Spleen length response was defined as the percentage of participants achieving a ≥50% reduction in spleen length at any visit relative to baseline as measured by palpation.
Week 24
Overall Response Rate (ORR)
Tidsramme: Week 24
ORR was defined as the percentage of participants with complete response (CR) or partial response (PR) (including the morphologic effects of the combination of zilurgisertib with ruxolitinib on bone marrow) according to Tefferi et al (2013) definitions.
Week 24
Progression-free Survival (PFS)
Tidsramme: Week 24
PFS was defined as the interval from the first dose of study treatment until the first documented progression or death according to Tefferi et al (2013) definitions.
Week 24
Leukemia-free Survival (LFS)
Tidsramme: Week 24
LFS was defined as the interval from the first dose of study treatment until the first documented leukemia transformation or death from any cause.
Week 24
Cmax of Zilurgisertib Alone
Tidsramme: Cycle 1 Day 1 (first dose) and Cycle 1 Day 15 (steady state): pre-dose and 2 hours, 4 hours, and 6-8 hours post-dose
Cmax was defined as the maximum concentration of zilurgisertib.
Cycle 1 Day 1 (first dose) and Cycle 1 Day 15 (steady state): pre-dose and 2 hours, 4 hours, and 6-8 hours post-dose
Tmax of Zilurgisertib
Tidsramme: Cycle 1 Day 1 (first dose) and Cycle 1 Day 15 (steady state): pre-dose and 2 hours, 4 hours, and 6-8 hours post-dose
tmax was defined as the time to the maximum concentration of zilurgisertib.
Cycle 1 Day 1 (first dose) and Cycle 1 Day 15 (steady state): pre-dose and 2 hours, 4 hours, and 6-8 hours post-dose
AUC0-t of Zilurgisertib
Tidsramme: Cycle 1 Day 1 (first dose) and Cycle 1 Day 15 (steady state): pre-dose and 2 hours, 4 hours, and 6-8 hours post-dose
AUC0-t was defined as the area under the plasma concentration-time curve from time 0 to the last quantifiable measurable plasma concentration of zilurgisertib.
Cycle 1 Day 1 (first dose) and Cycle 1 Day 15 (steady state): pre-dose and 2 hours, 4 hours, and 6-8 hours post-dose
Change From Baseline in Ferritin
Tidsramme: Baseline; Cycle 1 Day 8; Cycle 1 Day 15; Cycle 1 Day 22; Cycles 2, 3, 4, 5, 6, and 7 Day 1; Cycle 2 Day 15
Change from Baseline (CFB) was calculated as the post-Baseline value minus the Baseline value.
Baseline; Cycle 1 Day 8; Cycle 1 Day 15; Cycle 1 Day 22; Cycles 2, 3, 4, 5, 6, and 7 Day 1; Cycle 2 Day 15
Change From Baseline in Hemoglobin at the End of Treatment
Tidsramme: up to 1530 days
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
up to 1530 days

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Incyte Corporation

Efterforskere

  • Studieleder: Amanda McBride, MD, Incyte Corporation

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Hjælpsomme links

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

19. marts 2021

Primær færdiggørelse (Faktiske)

1. april 2025

Studieafslutning (Anslået)

26. november 2027

Datoer for studieregistrering

Først indsendt

19. juni 2020

Først indsendt, der opfyldte QC-kriterier

29. juni 2020

Først opslået (Faktiske)

2. juli 2020

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

14. maj 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

12. maj 2026

Sidst verificeret

1. maj 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • INCB 00928-104
  • 2020-004029-21 (EudraCT nummer)
  • 2023-503625-19-00 (Registry Identifier: EU CT Number)

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

JA

IPD-planbeskrivelse

Incyte deler data med kvalificerede eksterne forskere, efter at et forskningsforslag er indsendt. Disse anmodninger gennemgås og godkendes af et bedømmelsespanel på grundlag af videnskabelig fortjeneste. Alle opgivne data er anonymiseret for at respektere privatlivets fred for patienter, der har deltaget i forsøget i overensstemmelse med gældende love og regler.

Tilgængeligheden af ​​forsøgsdata er i overensstemmelse med kriterierne og processen beskrevet på https://www.incyte.com/our-company/compliance-and-transparency

IPD-delingstidsramme

Data vil blive delt efter den primære offentliggørelse eller 2 år efter undersøgelsen er afsluttet for markedsgodkendte produkter og indikationer.

IPD-delingsadgangskriterier

Data fra kvalificerede undersøgelser vil blive delt med kvalificerede forskere i henhold til kriterierne og processen beskrevet i afsnittet om datadeling på www.incyteclinicaltrials.com internet side. For godkendte anmodninger vil forskerne få adgang til anonymiserede data i henhold til en datadelingsaftale.

IPD-deling Understøttende informationstype

  • STUDY_PROTOCOL
  • SAP

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Kliniske forsøg med Anæmi

Kliniske forsøg med INCB000928

Søg i lignende forsøg

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

CROs by country

CROs in Panama

Betingelser

Sjældne sygdomme

Narkotikainterventioner

Kosttilskud

Sponsor / samarbejdspartnere

Placeringer

Abonner