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Trial record 1 of 1 for:    NCT03669965
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KRT-232 Compared to Ruxolitinib in Patients With Phlebotomy-Dependent Polycythemia Vera

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ClinicalTrials.gov Identifier: NCT03669965
Recruitment Status : Recruiting
First Posted : September 13, 2018
Last Update Posted : November 26, 2019
Sponsor:
Information provided by (Responsible Party):
Kartos Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE September 5, 2018
First Posted Date  ICMJE September 13, 2018
Last Update Posted Date November 26, 2019
Actual Study Start Date  ICMJE January 15, 2019
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 11, 2018)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03669965 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 11, 2018)
  • Duration of response after achieving both the absence of phlebotomy eligibility and reduction in spleen volume (for patients with splenomegaly) [ Time Frame: 4 years ]
  • Duration of response after achieving phlebotomy independence [ Time Frame: 4 years ]
  • Change from baseline of MPN-SAF TSS v2.0 patient-reported outcome [ Time Frame: 32 weeks ]
  • Change from baseline of EORTC-QLQ-C30 patient-reported outcome [ Time Frame: 32 weeks ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: September 11, 2018)
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 ]
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE KRT-232 Compared to Ruxolitinib in Patients With Phlebotomy-Dependent Polycythemia Vera
Official Title  ICMJE 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
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.

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 Polycythemia Vera
Intervention  ICMJE
  • Drug: KRT-232
    KRT-232, administered by mouth
  • Drug: Ruxolitinib
    Ruxolitinib per approved prescribing label
Study Arms  ICMJE
  • 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)
    Intervention: Drug: KRT-232
  • 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)
    Intervention: Drug: KRT-232
  • 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)
    Intervention: Drug: KRT-232
  • Experimental: Part B KRT-232 Arm
    Recommended KRT-232 dose and schedule from Part A
    Intervention: Drug: KRT-232
  • Active Comparator: Part B Ruxolitinib Arm
    Ruxolitinib per approved prescribing label
    Intervention: Drug: Ruxolitinib
  • 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)
    Intervention: Drug: KRT-232
  • 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)
    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: November 22, 2019)
322
Original Estimated Enrollment  ICMJE
 (submitted: September 11, 2018)
295
Estimated Study Completion Date  ICMJE October 2023
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
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 6505420136 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 NCT03669965
Other Study ID Numbers  ICMJE KRT-232-102
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
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 November 2019

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