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

• ClinicalTrials.gov Identifier: NCT03669965
• Recruitment Status: Active, not recruiting
• First Posted: September 13, 2018
• Last Update Posted: July 31, 2020
• Sponsor: Kartos Therapeutics, Inc.
• Information provided by (Responsible Party): Kartos Therapeutics, Inc.

Tracking Information

• First Submitted Date: September 5, 2018
• First Posted Date: September 13, 2018
• Last Update Posted Date: July 31, 2020
• Actual Study Start Date: January 15, 2019
• Estimated Primary Completion Date: April 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Same as current

Current Secondary Outcome Measures (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: 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: 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

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: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Polycythemia Vera

Intervention

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

Study Arms

• 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

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: July 30, 2020): 20
• Original Estimated Enrollment (submitted: September 11, 2018): 295
• Estimated Study Completion Date: October 2022
• Estimated Primary Completion Date: April 2022 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Germany, Hungary, Poland, Spain, United States
• Removed Location Countries: Canada, Czechia, United Kingdom

Administrative Information

• NCT Number: NCT03669965
• Other Study ID Numbers: 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: Not Provided
• Responsible Party: Kartos Therapeutics, Inc.
• Study Sponsor: Kartos Therapeutics, Inc.
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Kartos Therapeutics, Inc.
• Verification Date: July 2020