NCT04878003

Brief Summary

This study evaluates either KRT-232 or TL-895 in treatment naïve patients with myelofibrosis (MF) The study will be conducted in 2 stages. Stage 1 will evaluate safety, tolerability, and efficacy of either KRT-232 (Arm 1) or TL-895 (Arm 2) in treatment naïve patients. Stage 2 will expand enrollment in Arm 1 and/or Arm 2 if expansion criteria is met.

Trial Health

50
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
52

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Apr 2021

Typical duration for phase_2

Geographic Reach
9 countries

29 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 13, 2021

Completed
21 days until next milestone

First Submitted

Initial submission to the registry

May 4, 2021

Completed
3 days until next milestone

First Posted

Study publicly available on registry

May 7, 2021

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2024

Completed
1.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2025

Completed
Last Updated

May 9, 2022

Status Verified

May 1, 2022

Enrollment Period

3.1 years

First QC Date

May 4, 2021

Last Update Submit

May 5, 2022

Conditions

Keywords

navtemadlin

Outcome Measures

Primary Outcomes (1)

  • Spleen Volume Reduction (SVR)

    The proportion of subjects achieving ≥35% SVR at Week 24 by MRI/CT (central review)

    24 weeks

Secondary Outcomes (5)

  • Improvement in Total Symptom Score (TSS)

    24 weeks

  • Spleen Response Duration

    48 months

  • Rate of conversion from RBC transfusion dependent to independent

    24 weeks

  • Overall Survival (OS)

    48 months

  • Progression free survival (PFS)

    48 months

Study Arms (2)

Arm 1

EXPERIMENTAL

KRT-232 administered orally as 240 mg once daily on Days 1-7, off treatment on Days 8-28, in 28-day treatment cycles

Drug: KRT-232

Arm 2

EXPERIMENTAL

TL-895 administered orally as 150 mg twice daily continuously in 28-day cycles

Drug: TL-895

Interventions

KRT-232, administration by mouth

Arm 1
TL-895DRUG

TL-895, administration by mouth

Arm 2

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Confirmed diagnosis of PMF, post-PV MF or post-ET MF (WHO)
  • High-risk, or intermediate-1 and 2 risk, defined by Dynamic International Prognostic System (DIPSS)
  • ECOG of 0 or 1

You may not qualify if:

  • Subjects who are positive for p53 mutation (Arm 1)
  • Prior MDM2 inhibitor therapy or p53-directed therapy (Arm 1)
  • Prior treatment with any JAK inhibitor
  • Prior splenectomy
  • Splenic irradiation within 24 weeks prior to randomization
  • Prior allogeneic stem-cell transplantation or plans for allogeneic stem-cell transplant
  • History of major organ transplant
  • Grade 2 or higher QTc prolongation
  • Major hemorrhage or intracranial hemorrhage within 24 weeks prior to randomization

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (29)

Innovative Clinical Research Institute

Glendale, California, 90603, United States

RECRUITING

Innovative Clinical Research Institute

Whittier, California, 90603, United States

RECRUITING

Gabrail Cancer Center

Canton, Ohio, 44718, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Republican Scientific Practical Center of Radiation Medicine and Human Ecology

Belarus’, 246040, Belarus

RECRUITING

Minsk Scientific and Practice Center of Surgery, Transplantology and Hematology

Minsk, 220045, Belarus

RECRUITING

UMHAT Georgi Stranski

Pleven, 5800, Bulgaria

RECRUITING

Medical Centre Hipokrat N

Plovdiv, 4000, Bulgaria

RECRUITING

UMHAT Sv. Ivan Rilski EAD

Sofia, 1431, Bulgaria

RECRUITING

Military Medical Academy

Sofia, 1606, Bulgaria

RECRUITING

Specialized Hospital for Active Treatment of Hematologic Diseases

Sofia, 1756, Bulgaria

RECRUITING

JSC EVEX Hospitals

Kutaisi, 4600, Georgia

RECRUITING

LTD M.Zodelava Hematology Centre

Tbilisi, 112, Georgia

RECRUITING

K.Eristavi National Center of Experimental and Clinical Surgery

Tbilisi, 159, Georgia

RECRUITING

Centro de Investigacion Medica Aquascalientes (CIMA)

Aguascalientes, 20116, Mexico

RECRUITING

Unidad de Investigacion CIMA SC

Chihuahua City, 31200, Mexico

RECRUITING

Centro de Investigacion Clinica de Oaxaca (CICLO)

Oaxaca City, 68020, Mexico

RECRUITING

Sociedad de Metabolismo Y Corazon - SOMECO

Veracruz, 91900, Mexico

RECRUITING

Samodzielny Publiczny Zakład Opieki Zdrowotnej Zespół Szpitali Miejskich

Katowice, 40-519, Poland

RECRUITING

Szpital Wojewodzki w Opolu Sp. z o.o., Oddzial Hematologii i Onkologii Hematologicznej

Opole, 45-061, Poland

RECRUITING

Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku Sp. z o.o.

Słupsk, 76-200, Poland

RECRUITING

Botkin City Clinical Hospital

Moscow, 125284, Russia

RECRUITING

Republican Hospital n.a. V.A. Baranov

Petrozavodsk, 185019, Russia

RECRUITING

Pavlov First Saint Petersburg State Medical University

Saint Petersburg, 197022, Russia

RECRUITING

Almazov National Medical Research Center

Saint Petersburg, 197341, Russia

RECRUITING

Almazov National Medical Research Centre

Saint Petersburg, 197341, Russia

RECRUITING

Samara State Medical University

Samara, 443099, Russia

RECRUITING

Wits Baragwanath Clinical Hematology Department

Soweto, 1519, South Africa

RECRUITING

City Hematology Center of Municipal Non-Profit Enterprise City Clinical Hospital #4 of Dnipro City Council

Dnipro, 49102, Ukraine

RECRUITING

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

navtemadlin; 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(isopropylsulfonyl)-3-methylbutan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid

Condition Hierarchy (Ancestors)

Myeloproliferative DisordersBone Marrow DiseasesHematologic DiseasesHemic and Lymphatic Diseases

Central Study Contacts

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 4, 2021

First Posted

May 7, 2021

Study Start

April 13, 2021

Primary Completion

May 1, 2024

Study Completion

October 1, 2025

Last Updated

May 9, 2022

Record last verified: 2022-05

Locations