KRT-232 Compared to Ruxolitinib in Patients With Phlebotomy-Dependent Polycythemia Vera

July 30, 2020 updated by: Kartos Therapeutics, Inc.

A Two-Part, Randomized, Open-label, Multicenter, Phase 2a/2b Study of the Efficacy, Safety, and Pharmacokinetics of KRT-232 Compared to Ruxolitinib in Patients With Phlebotomy-Dependent Polycythemia Vera

This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, for the treatment of patients with phlebotomy-dependent polycythemia vera (PV). Inhibition of MDM2 in PV is a new mechanism of action in PV. In Part A, patients must be resistant or intolerant to hydroxyurea or have undergone treatment with interferon. In Part B, patients must be resistant or intolerant to hydroxyurea.

This study is a global, open-label Phase 2a/2b study to determine the efficacy and safety of KRT-232. In Part A of the study, patients will be randomly assigned to 5 arms with 2 different doses and 3 different dosing schedules of KRT 232. In Part B of the study, patients will be randomized either to treatment with KRT-232 administered at the recommended dose and schedule from Part A or to treatment with ruxolitinib.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Angers, France, 49933 Cedex 09
        • Center Hospitalier Universitaire d'Angers
  • Germany
      • Mutlangen, Germany, 73557
        • Stauferklinikum Schwäbisch Gmünd
    • Nordrhein-westfalen
      • Aachen, Nordrhein-westfalen, Germany
        • Universitätsklinikum Aachen
    • Sachsen
      • Dresden, Sachsen, Germany
        • Universitätsklinikum Carl Gustav Carus
      • Dresden, Sachsen, Germany
        • Gemeinschaftspraxis Haematologie - Onkologie - Hauptstelle
  • Hungary
      • Gyula, Hungary, 5700
        • Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaz
  • Poland
      • Opole, Poland, 45-061
        • Szpital Wojewodzki w Opolu
    • Dolnoslaskie
      • Wrocław, Dolnoslaskie, Poland
        • Dolnośląskie Centrum Transplantacji Komórkowych z Krajowym Bankiem Dawców Szpiku
  • Spain
      • Málaga, Spain, 29010
        • Hospital Universitario Virgen de la Victoria
      • Salamanca, Spain, 37007
        • Hospital Universitario de Salamanca
    • LAS Palmas
      • Las Palmas de Gran Canaria, LAS Palmas, Spain
        • Hospital Universitario de Gran Canaria Doctor Negrin
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35249
        • The Kirklin Clinic of Uab Hospital
    • California
      • Los Angeles, California, United States, 90033
        • University of Southern California Norris Comprehensive Cancer Center
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • Ohio
      • Canton, Ohio, United States, 44718
        • Gabrail Cancer Center
      • Columbus, Ohio, United States, 43210
        • The Ohio State University Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Confirmed diagnosis of PV (WHO 2016)
  • ECOG ≤ 2
  • Part A: patients with and without splenomegaly are eligible
  • Part A: patients must be resistant or intolerant to hydroxyurea or have undergone treatment with interferon
  • Part B: only patients with splenomegaly are eligible
  • Part B: patients must be resistant or intolerant to hydroxyurea

Exclusion Criteria:

  • Diagnosis of post-PV myelofibrosis (IWG-MRT)
  • Prior treatment with MDM2 inhibitors, p53-directed therapies, HDAC, BCL 2 inhibitors
  • Splenic irradiation within 3 months prior to the first dose of study treatment
  • Clinically significant thrombosis within 3 months of screening
  • Grade 2 or higher QTc prolongation
  • Part B: prior treatment with a JAK inhibitor

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part A Arm 1
KRT-232 120mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)
Drug: KRT-232
KRT-232, administered by mouth
Experimental: Part A Arm 2
KRT-232 240mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)
Drug: KRT-232
KRT-232, administered by mouth
Experimental: Part A Arm 3
KRT-232 120mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles)
Drug: KRT-232
KRT-232, administered by mouth
Experimental: Part B KRT-232 Arm
Recommended KRT-232 dose and schedule from Part A
Drug: KRT-232
KRT-232, administered by mouth
Active Comparator: Part B Ruxolitinib Arm
Ruxolitinib per approved prescribing label
Drug: Ruxolitinib
Ruxolitinib per approved prescribing label
Experimental: Part A Arm 4b
KRT-232 240mg by mouth once daily for Days 1-5, off treatment for Days 6-28 (28-day cycles)
Drug: KRT-232
KRT-232, administered by mouth
Experimental: Part A Arm 2b
KRT-232 240mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles)
Drug: KRT-232
KRT-232, administered by mouth

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patients with splenomegaly achieving a response at Week 32
Time Frame: 32 weeks

Response defined as having achieved both of the following:

  • The absence of phlebotomy eligibility beginning at the Week 8 visit and continuing through Week 32, with no more than one phlebotomy eligibility occurring post-randomization and prior to the Week 8 visit
  • A reduction in spleen volume as assessed by MRI (or CT) ≥ 35% from baseline at Week 32
32 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Duration of response after achieving both the absence of phlebotomy eligibility and reduction in spleen volume (for patients with splenomegaly)
Time Frame: 4 years
4 years
Duration of response after achieving phlebotomy independence
Time Frame: 4 years
4 years
Change from baseline of MPN-SAF TSS v2.0 patient-reported outcome
Time Frame: 32 weeks
32 weeks
Change from baseline of EORTC-QLQ-C30 patient-reported outcome
Time Frame: 32 weeks
32 weeks

Other Outcome Measures

Outcome Measure
Time Frame
Proportion of patients without splenomegaly achieving the absence of phlebotomy eligibility beginning at the Week 8 and continuing through Week 28, with no more than one phlebotomy eligibility occurring post-randomization and prior to Week 8
Time Frame: 28 weeks
28 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kartos Therapeutics, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 15, 2019

Primary Completion (Anticipated)

April 1, 2022

Study Completion (Anticipated)

October 1, 2022

Study Registration Dates

First Submitted

September 5, 2018

First Submitted That Met QC Criteria

September 11, 2018

First Posted (Actual)

September 13, 2018

Study Record Updates

Last Update Posted (Actual)

July 31, 2020

Last Update Submitted That Met QC Criteria

July 30, 2020

Last Verified

July 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KRT-232-102

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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