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INCB000928 Podáváno jako monoterapie nebo v kombinaci s ruxolitinibem u pacientů s anémií způsobenou myeloproliferativními poruchami

9. září 2026 aktualizováno: Incyte Corporation

Otevřená, multicentrická studie fáze 1/2 INCB000928 podávaná jako monoterapie nebo v kombinaci s ruxolitinibem u účastníků s anémií způsobenou myeloproliferativními poruchami

This Phase 1/2, open-label, dose-finding study is intended to evaluate the safety and tolerability, PK, PD, and efficacy of INCB000928 administered as monotherapy or in combination with ruxolitinib in participants with MF who are transfusion-dependent or presenting with symptomatic anemia. This study will consist of 2 parts: dose escalation and expansion.

Přehled studie

Postavení

Dokončeno

Podmínky

Intervence / Léčba

Typ studie

Intervenční

Zápis (Aktuální)

84

Fáze

  • Fáze 2
  • Fáze 1

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní místa

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

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

18 let a starší (Dospělý, Starší dospělý)

Přijímá zdravé dobrovolníky

Ne

Pohlaví způsobilá ke studiu

Všechno

Popis

Inclusion Criteria:

  • Participants with MF who are transfusion-dependent or present with symptomatic anemia, defined as follows:

    1. Anemia: An Hgb value < 10 g/dL demonstrated during screening recorded on 3 separate occasions with at least 7 days between measurements (Note: RBC transfusion must be at least 2 weeks before the Hgb measurement during screening).
    2. Transfusion-dependent: Participant has received at least 4 units of RBC transfusions during the 28 days immediately preceding Cycle 1 Day 1 OR has received an average of at least 4 units of RBC transfusions in the 8 weeks immediately preceding Cycle 1 Day 1, for an Hgb level of < 8.5 g/dL, in the absence of bleeding or treatment-induced anemia. In addition, the most recent transfusion episode must have occurred in the 28 days before Cycle 1 Day 1.

  • ECOG performance status score of the following:

    1. 0 or 1 for the dose-escalation stages.
    2. 0, 1, or 2 for the dose-expansion stage.

  • Life expectancy is greater than 6 months

  • Agreement to avoid pregnancy or fathering children.

  • Ineligible to receive or have not responded to available therapies for anemia such as ESAs.

  • For TGA:

  • Participants previously treated with JAK inhibitors for at least 12 weeks.

  • Participants with intermediate-2 or high DIPSS MF according to IWG-MRT criteria.

  • For TGB:

  • Participants must have been on a therapeutic and stable regimen of ruxolitinib for at least 12 consecutive weeks immediately preceding the first dose of study treatment.

  • Participants with intermediate-1, intermediate-2, or high DIPSS MF according to IWG-MRT criteria.

  • For TGC:

  • Participants must be JAK inhibitor treatment naive (no prior treatment with any JAK inhibitor) and have an indication for initiation of ruxolitinib treatment.

  • Participants with intermediate-1, intermediate-2, or high DIPSS MF according to IWG-MRT criteria.

Exclusion Criteria:

  • Undergone any prior allogenic or autologous stem cell transplantation or a candidate for such transplantation.
  • Any prior chemotherapy, immunomodulatory drug therapy, immunosuppressive therapy, biological therapy, endocrine therapy, targeted therapy, antibody or hypomethylating agent to treat the participant's disease, with the exception of ruxolitinib for TGB only, within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment.
  • Laboratory Values outside of protocol defined range at screening.

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Léčba
  • Přidělení: Nerandomizované
  • Intervenční model: Sekvenční přiřazení
  • Maskování: Žádné (otevřený štítek)

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Experimentální: Treatment Group A (TGA)

INCB000928 will be administered once daily (QD).
Lék: INCB000928

INCB000928 will be administered at protocol defined dose.
Experimentální: Treatment Group B (TGB)

INCB000928 will be administered in combination with ruxolitinib.
Lék: INCB000928

INCB000928 will be administered at protocol defined dose.

Lék: ruxolitinib

Ruxolitinib will be administered at protocol defined dose.
Experimentální: Treatment Group C (TGC)

INCB000928 will be administered in combination with ruxolitinib.
Lék: INCB000928

INCB000928 will be administered at protocol defined dose.

Lék: ruxolitinib

Ruxolitinib will be administered at protocol defined dose.

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Treatment-emergent Serious Adverse Event (SAE)
Časové okno: 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
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Percentage of Participants With Anemia Response
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Percentage Change in Hepcidin From Cycle 1 Day 15 to Cycle 7 Day 1
Časové okno: from Cycle 1 Day 15 to Cycle 7 Day 1

Percentage change was calculated as the ([post-baseline value minus the baseline value] / [baseline value]) * 100.
from Cycle 1 Day 15 to Cycle 7 Day 1
Change From Baseline in Ferritin
Časové okno: 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
Časové okno: up to 1530 days

Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
up to 1530 days

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

Incyte Corporation

Vyšetřovatelé

  • Ředitel studie: Amanda McBride, MD, Incyte Corporation

Publikace a užitečné odkazy

Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.

Obecné publikace

Užitečné odkazy

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia (Aktuální)

19. března 2021

Primární dokončení (Aktuální)

1. dubna 2025

Dokončení studie (Aktuální)

8. září 2026

Termíny zápisu do studia

První předloženo

19. června 2020

První předloženo, které splnilo kritéria kontroly kvality

29. června 2020

První zveřejněno (Aktuální)

2. července 2020

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Aktuální)

1. října 2026

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

9. září 2026

Naposledy ověřeno

1. září 2026

Více informací

Termíny související s touto studií

Klíčová slova

Další relevantní podmínky MeSH

Další identifikační čísla studie

  • INCB 00928-104
  • 2020-004029-21 (Číslo EudraCT)
  • 2023-503625-19-00 (Identifikátor registru: EU CT Number)
  • 2023 (Grant/smlouva NIH USA)

Plán pro data jednotlivých účastníků (IPD)

Plánujete sdílet data jednotlivých účastníků (IPD)?

ANO

Popis plánu IPD

Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency

Časový rámec sdílení IPD

Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.

Kritéria přístupu pro sdílení IPD

Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.

Typ podpůrných informací pro sdílení IPD

  • PROTOKOL STUDY
  • MÍZA

Informace o lécích a zařízeních, studijní dokumenty

Studuje lékový produkt regulovaný americkým FDA

Ano

Studuje produkt zařízení regulovaný americkým úřadem FDA

Ne

Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .

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