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

Primary Purpose

Polycythemia Vera

Status
Unknown status
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
KRT-232
Ruxolitinib
Sponsored by
Kartos Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Polycythemia Vera

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • The Kirklin Clinic of UAB Hospital
  • University of Southern California Norris Comprehensive Cancer Center
  • Washington University School of Medicine
  • Gabrail Cancer Center
  • The Ohio State University Comprehensive Cancer Center
  • Center Hospitalier Universitaire d'Angers
  • Universitätsklinikum Aachen
  • Gemeinschaftspraxis Haematologie - Onkologie - Hauptstelle
  • Universitätsklinikum Carl Gustav Carus
  • Stauferklinikum Schwäbisch Gmünd
  • Békés Megyei Központi Kórház Pándy Kálmán Tagkórház
  • Dolnośląskie Centrum Transplantacji Komórkowych z Krajowym Bankiem Dawców Szpiku
  • Szpital Wojewódzki w Opolu
  • Hospital Universitario de Gran Canaria Doctor Negrin
  • Hospital Universitario Virgen de la Victoria
  • Hospital Universitario de Salamanca

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Experimental

Experimental

Experimental

Active Comparator

Experimental

Experimental

Arm Label

Part A Arm 1

Part A Arm 2

Part A Arm 3

Part B KRT-232 Arm

Part B Ruxolitinib Arm

Part A Arm 4b

Part A Arm 2b

Arm Description

KRT-232 120mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)

KRT-232 240mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)

KRT-232 120mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles)

Recommended KRT-232 dose and schedule from Part A

Ruxolitinib per approved prescribing label

KRT-232 240mg by mouth once daily for Days 1-5, off treatment for Days 6-28 (28-day cycles)

KRT-232 240mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles)

Outcomes

Primary Outcome Measures

Proportion of patients with splenomegaly achieving a response at Week 32
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

Secondary Outcome Measures

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

Full Information

First Posted
September 5, 2018
Last Updated
July 30, 2020
Sponsor
Kartos Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03669965
Brief Title
KRT-232 Compared to Ruxolitinib in Patients With Phlebotomy-Dependent Polycythemia Vera
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2020
Overall Recruitment Status
Unknown status
Study Start Date
January 15, 2019 (Actual)
Primary Completion Date
April 2022 (Anticipated)
Study Completion Date
October 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kartos Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polycythemia Vera

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part A Arm 1
Arm Type
Experimental
Arm Description
KRT-232 120mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)
Arm Title
Part A Arm 2
Arm Type
Experimental
Arm Description
KRT-232 240mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)
Arm Title
Part A Arm 3
Arm Type
Experimental
Arm Description
KRT-232 120mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles)
Arm Title
Part B KRT-232 Arm
Arm Type
Experimental
Arm Description
Recommended KRT-232 dose and schedule from Part A
Arm Title
Part B Ruxolitinib Arm
Arm Type
Active Comparator
Arm Description
Ruxolitinib per approved prescribing label
Arm Title
Part A Arm 4b
Arm Type
Experimental
Arm Description
KRT-232 240mg by mouth once daily for Days 1-5, off treatment for Days 6-28 (28-day cycles)
Arm Title
Part A Arm 2b
Arm Type
Experimental
Arm Description
KRT-232 240mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles)
Intervention Type
Drug
Intervention Name(s)
KRT-232
Intervention Description
KRT-232, administered by mouth
Intervention Type
Drug
Intervention Name(s)
Ruxolitinib
Intervention Description
Ruxolitinib per approved prescribing label
Primary Outcome Measure Information:
Title
Proportion of patients with splenomegaly achieving a response at Week 32
Description
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
Time Frame
32 weeks
Secondary Outcome Measure Information:
Title
Duration of response after achieving both the absence of phlebotomy eligibility and reduction in spleen volume (for patients with splenomegaly)
Time Frame
4 years
Title
Duration of response after achieving phlebotomy independence
Time Frame
4 years
Title
Change from baseline of MPN-SAF TSS v2.0 patient-reported outcome
Time Frame
32 weeks
Title
Change from baseline of EORTC-QLQ-C30 patient-reported outcome
Time Frame
32 weeks
Other Pre-specified Outcome Measures:
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
The Kirklin Clinic of UAB Hospital
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35249
Country
United States
Facility Name
University of Southern California Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Gabrail Cancer Center
City
Canton
State/Province
Ohio
ZIP/Postal Code
44718
Country
United States
Facility Name
The Ohio State University Comprehensive Cancer Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Center Hospitalier Universitaire d'Angers
City
Angers
ZIP/Postal Code
49933 Cedex 09
Country
France
Facility Name
Universitätsklinikum Aachen
City
Aachen
State/Province
Nordrhein-westfalen
Country
Germany
Facility Name
Gemeinschaftspraxis Haematologie - Onkologie - Hauptstelle
City
Dresden
State/Province
Sachsen
Country
Germany
Facility Name
Universitätsklinikum Carl Gustav Carus
City
Dresden
State/Province
Sachsen
Country
Germany
Facility Name
Stauferklinikum Schwäbisch Gmünd
City
Mutlangen
ZIP/Postal Code
73557
Country
Germany
Facility Name
Békés Megyei Központi Kórház Pándy Kálmán Tagkórház
City
Gyula
ZIP/Postal Code
5700
Country
Hungary
Facility Name
Dolnośląskie Centrum Transplantacji Komórkowych z Krajowym Bankiem Dawców Szpiku
City
Wrocław
State/Province
Dolnoslaskie
Country
Poland
Facility Name
Szpital Wojewódzki w Opolu
City
Opole
ZIP/Postal Code
45-061
Country
Poland
Facility Name
Hospital Universitario de Gran Canaria Doctor Negrin
City
Las Palmas de Gran Canaria
State/Province
LAS Palmas
Country
Spain
Facility Name
Hospital Universitario Virgen de la Victoria
City
Málaga
ZIP/Postal Code
29010
Country
Spain
Facility Name
Hospital Universitario de Salamanca
City
Salamanca
ZIP/Postal Code
37007
Country
Spain

12. IPD Sharing Statement

Learn more about this trial

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

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