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

Polycythemia Vera Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03669965
• Other study ID #: KRT-232-102
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 15, 2019
• Est. completion date: October 2022

Study information

• Verified date: July 2020
• Source: Kartos Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 20
• Est. completion date: October 2022
• Est. primary completion date: April 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Polycythemia
• Polycythemia Vera

Intervention

Drug:
• KRT-232
KRT-232, administered by mouth
• Ruxolitinib
Ruxolitinib per approved prescribing label

Locations

Country	Name	City	State
France	Center Hospitalier Universitaire d'Angers	Angers
Germany	Universitätsklinikum Aachen	Aachen	Nordrhein-westfalen
Germany	Gemeinschaftspraxis Haematologie - Onkologie - Hauptstelle	Dresden	Sachsen
Germany	Universitätsklinikum Carl Gustav Carus	Dresden	Sachsen
Germany	Stauferklinikum Schwäbisch Gmünd	Mutlangen
Hungary	Békés Megyei Központi Kórház Pándy Kálmán Tagkórház	Gyula
Poland	Szpital Wojewódzki w Opolu	Opole
Poland	Dolnoslaskie Centrum Transplantacji Komórkowych z Krajowym Bankiem Dawców Szpiku	Wroclaw	Dolnoslaskie
Spain	Hospital Universitario de Gran Canaria Doctor Negrin	Las Palmas de Gran Canaria	LAS Palmas
Spain	Hospital Universitario Virgen de la Victoria	Málaga
Spain	Hospital Universitario de Salamanca	Salamanca
United States	The Kirklin Clinic of UAB Hospital	Birmingham	Alabama
United States	Gabrail Cancer Center	Canton	Ohio
United States	The Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	University of Southern California Norris Comprehensive Cancer Center	Los Angeles	California
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Kartos Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  France,  Germany,  Hungary,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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		28 weeks
Primary	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	32 weeks
Secondary	Duration of response after achieving both the absence of phlebotomy eligibility and reduction in spleen volume (for patients with splenomegaly)		4 years
Secondary	Duration of response after achieving phlebotomy independence		4 years
Secondary	Change from baseline of MPN-SAF TSS v2.0 patient-reported outcome		32 weeks
Secondary	Change from baseline of EORTC-QLQ-C30 patient-reported outcome		32 weeks