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KRT-232 in Subjects With PMF, Post-PV MF, or Post-ET MF Who Have Failed a JAK Inhibitor

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ClinicalTrials.gov Identifier: NCT03662126
Recruitment Status : Recruiting
First Posted : September 7, 2018
Last Update Posted : July 30, 2019
Sponsor:
Information provided by (Responsible Party):
Kartos Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE September 5, 2018
First Posted Date  ICMJE September 7, 2018
Last Update Posted Date July 30, 2019
Actual Study Start Date  ICMJE January 15, 2019
Estimated Primary Completion Date August 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 5, 2018)
To determine spleen response [ Time Frame: 24 weeks ]
The proportion of patients achieving a ≥ 35% spleen volume reduction from Baseline to Week 24, as assessed by magnetic resonance imaging (MRI) or computed tomography (CT) scan
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03662126 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 5, 2018)
  • To determine the change in modified MPN-SAF Total Symptom Score (TSS) at Week 24 and Week 48 [ Time Frame: 48 weeks ]
    Proportion of patients who have at least a 50% reduction from Baseline to Week 24 and Week 48 in the total symptom score as measured by the modified MPN-SAF v2.0
  • RBC transfusion independence at Week 24 [ Time Frame: 24 weeks ]
    Proportion of patients who have RBC transfusion independence at week 24
  • Complete remission and partial remission defined according to International Working Group-Myeloproliferative Neoplasms Research and Treatment and modified European LeukemiaNet criteria [ Time Frame: 24 weeks ]
    Proportion of patients who have complete remission and partial remission at week 24
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE KRT-232 in Subjects With PMF, Post-PV MF, or Post-ET MF Who Have Failed a JAK Inhibitor
Official Title  ICMJE An Open-Label, Phase 2a/2b Study of KRT-232 in Subjects With Primary Myelofibrosis (PMF), Post-Polycythemia Vera MF (Post-PV-MF), Or Post-Essential Thrombocythemia MF (Post-ET-MF) Who Have Failed a JAK Inhibitor
Brief Summary

This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, for the treatment of patients with myelofibrosis (MF) who no longer benefit from treatment with JAK inhibitor. Inhibition of MDM2 is a novel mechanism of action in MF.

This study is a global, open-label Phase 2 study to determine the efficacy and safety of KRT-232 in patients with primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF who have failed previous treatment with JAK inhibitor (Part A), or Ruxolitinib (Part B). In Part A of the study, patients will be randomly assigned to 2 different doses and 2 different dosing schedules of KRT-232. In Part B of the study, patients will be treated at the recommended dose and schedule from Part A.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Primary Myelofibrosis (PMF)
  • Post-Polycythemia Vera MF (Post-PV-MF)
  • Post-Essential Thrombocythemia MF (Post-ET-MF)
Intervention  ICMJE Drug: KRT-232
KRT-232, administered by mouth
Study Arms  ICMJE
  • Experimental: Part A Cohort 1
    KRT-232 120mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)
    Intervention: Drug: KRT-232
  • Experimental: Part A Cohort 2
    KRT-232 240mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)
    Intervention: Drug: KRT-232
  • Experimental: Part A Cohort 3
    KRT-232 240mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles)
    Intervention: Drug: KRT-232
  • Experimental: Part B
    Recommended KRT-232 dose and schedule from Part A
    Intervention: Drug: KRT-232
  • Experimental: Part A Cohort 4
    KRT-232 360mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)
    Intervention: Drug: KRT-232
  • Experimental: Part A Cohort 5
    KRT-232 180mg by mouth once daily for Days 1-7, off treatment for Days 8-14, on treatment for Days 15-21, off treatment for Days 22-28 (28-day cycles)
    Intervention: Drug: KRT-232
  • Experimental: Part A Cohort 6
    KRT-232 120mg by mouth once daily for Days 1-14, off treatment for Days 15-21 (21-day cycles)
    Intervention: Drug: KRT-232
  • Experimental: Part A Cohort 7
    KRT-232 60mg by mouth once daily for Days 1-21, off treatment for Days 22-28 (28-day cycles)
    Intervention: Drug: KRT-232
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 18, 2019)
247
Original Estimated Enrollment  ICMJE
 (submitted: September 5, 2018)
190
Estimated Study Completion Date  ICMJE February 28, 2023
Estimated Primary Completion Date August 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Confirmed diagnosis of PMF, post-PV MF or post-ET MF (WHO)
  • High, intermediate-2, or intermediate-1 risk Dynamic International Prognostic System (DIPSS)
  • Failure of prior treatment with JAK inhibitor (Part A) or ruxolitinib (Part B)
  • ECOG ≤ 2

Exclusion Criteria:

  • Prior splenectomy
  • Splenic irradiation within 3 months prior to the first dose of KRT-232
  • Active or chronic bleeding within 4 weeks prior to the first dose of KRT-232
  • Prior MDM2 inhibitor therapy or p53-directed therapy
  • Prior treatment with HDAC or BCL-2 inhibitors
  • Grade 2 or higher QTc prolongation (> 480 milliseconds per NCI-CTCAE criteria, version 5.0)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: John Mei 650-542-0136 jmei@kartosthera.com
Listed Location Countries  ICMJE Canada,   Czechia,   France,   Germany,   Hungary,   Poland,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03662126
Other Study ID Numbers  ICMJE KRT-232-101
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Kartos Therapeutics, Inc.
Study Sponsor  ICMJE Kartos Therapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Kartos Therapeutics, Inc.
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP