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INCB000928 Administrert som monoterapi eller i kombinasjon med ruxolitinib hos deltakere med anemi på grunn av myeloproliferative lidelser

9. september 2026 oppdatert av: Incyte Corporation

En fase 1/2 åpen, multisenterstudie av INCB000928 administrert som monoterapi eller i kombinasjon med ruxolitinib hos deltakere med anemi på grunn av myeloproliferative lidelser

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.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Studietype

Intervensjonell

Registrering (Faktiske)

84

Fase

  • Fase 2
  • Fase 1

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Cancer Center
    • Quebec
      • Montreal, Quebec, Canada, H3T1E2
        • McGill University Jewish General Hospital
  • Forente stater
    • California
      • Duarte, California, Forente stater, 91010
        • City of Hope National Medical Center
      • Irvine, California, Forente stater, 92618
        • City of Hope Orange County
      • Los Angeles, California, Forente stater, 90089
        • Usc Norris Comprehensive Cancer Center
      • Palo Alto, California, Forente stater, 94304
        • Stanford Cancer Center
      • San Diego, California, Forente stater, 92103
        • Prebys Cancer Center
    • Georgia
      • Atlanta, Georgia, Forente stater, 30322
        • Emory University - Winship Cancer Institute
      • Atlanta, Georgia, Forente stater, 30322
        • Emory University-Winship Cancer Institute
    • Michigan
      • Grand Rapids, Michigan, Forente stater, 49546
        • Start Midwest
    • Missouri
      • St Louis, Missouri, Forente stater, 63110
        • Washington University School of Medicine
    • New York
      • New York, New York, Forente stater, 10065
        • Weill Cornell Medical Centers
    • North Carolina
      • Durham, North Carolina, Forente stater, 27705
        • Duke University Medical Center, Department of Hematologic Malignancies and Cellular Therapy
    • Tennessee
      • Nashville, Tennessee, Forente stater, 37232
        • Vanderbilt University Medical Center
    • Texas
      • Houston, Texas, Forente stater, 77030
        • Md Anderson Cancer Center
  • Frankrike
      • Angers, Frankrike, 49033
        • Centre Hospitalier D'Angers
      • Marseille, Frankrike, 13273
        • Institut Paoli Calmettes
      • Paris, Frankrike, 75010
        • Hospital Saint Louis
  • Italia
      • Bergamo, Italia, 24127
        • Azienda Ospedaliera Papa Giovanni Xxiii
      • Bologna, Italia, 40138
        • S Orsolas University Hospital Seragnoli Institute of Hematology
      • Florence, Italia, 50134
        • Azienda Ospedaliero-Universitaria Careggi (Aouc)
      • Orbassano, Italia, 10043
        • Azienda Ospedaliera Universitaria San Luigi Gonzaga Orbassano
      • Pavia, Italia, 27100
        • Comitato Di Bioetica Della Fondazione Irccs Policlinico San Matteo
      • Perugia, Italia, 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
  • Storbritannia
      • Boston, Storbritannia, PE21 9QS
        • United Lincolnshire Hospitals
      • Lincoln, Storbritannia, LN2 5QY
        • Lincoln County Hospital
      • Truro, Storbritannia, TR1 3LJ
        • Royal Cornwall Hospital Truro Sunrise Centre
    • WLS
      • Cardiff, WLS, Storbritannia, CF14 4XW
        • University Hospital of Wales

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

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.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomisert
  • Intervensjonsmodell: Sekvensiell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Treatment Group A (TGA)

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

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

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

INCB000928 will be administered at protocol defined dose.

Legemiddel: ruxolitinib

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

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

INCB000928 will be administered at protocol defined dose.

Legemiddel: ruxolitinib

Ruxolitinib will be administered at protocol defined dose.

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
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
Tiltaksbeskrivelse
Tidsramme
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
Percentage Change in Hepcidin From Cycle 1 Day 15 to Cycle 7 Day 1
Tidsramme: 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
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

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Incyte Corporation

Etterforskere

  • Studieleder: Amanda McBride, MD, Incyte Corporation

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Hjelpsomme linker

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

19. mars 2021

Primær fullføring (Faktiske)

1. april 2025

Studiet fullført (Faktiske)

8. september 2026

Datoer for studieregistrering

Først innsendt

19. juni 2020

Først innsendt som oppfylte QC-kriteriene

29. juni 2020

Først lagt ut (Faktiske)

2. juli 2020

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

1. oktober 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

9. september 2026

Sist bekreftet

1. september 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • INCB 00928-104
  • 2020-004029-21 (EudraCT-nummer)
  • 2023-503625-19-00 (Registeridentifikator: EU CT Number)
  • 2023 (U.S. NIH-stipend/kontrakt)

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

JA

IPD-planbeskrivelse

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

IPD-delingstidsramme

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

Tilgangskriterier for IPD-deling

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.

IPD-deling Støtteinformasjonstype

  • STUDY_PROTOCOL
  • SEVJE

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Ja

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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