Polycythemia Vera
Conditions
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.
Interventions
DRUGKRT-232
KRT-232, administered by mouth
DRUGRuxolitinib
Ruxolitinib per approved prescribing label
Sponsors
Kartos Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients with splenomegaly achieving a response at Week 32 | 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 |
Secondary
| Measure | Time frame |
|---|---|
| Duration of response after achieving both the absence of phlebotomy eligibility and reduction in spleen volume (for patients with splenomegaly) | 4 years |
| Duration of response after achieving phlebotomy independence | 4 years |
| Change from baseline of MPN-SAF TSS v2.0 patient-reported outcome | 32 weeks |
| Change from baseline of EORTC-QLQ-C30 patient-reported outcome | 32 weeks |
Other
| 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 | 28 weeks |
Countries
France, Germany, Hungary, Poland, Spain, United States
Outcome results
None listed