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

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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
        • Universitatsklinikum 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 Negrín
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 15, 2019

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2022

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 5, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 11, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 13, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 31, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 30, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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