Polycythemia VeraPhase 2NCT03669965
KRT-232 Compared to Ruxolitinib in Patients With Phlebotomy-Dependent Polycythemia Vera
A Phase 2 study testing KRT-232 and Ruxolitinib in people with Polycythemia Vera, run by Kartos Therapeutics, Inc. at 16 sites in 6 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Polycythemia Vera
- What is being tested?
- KRT-232 and Ruxolitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 16 sitesin 6 countries
- Study dates
- 15 Jan 2019to Oct 2022
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
16 sites in 6 countries.
16 sites in 6 countries
United States5 sites
The Kirklin Clinic of UAB Hospital
Birmingham, Alabama, 35249
Gabrail Cancer Center
Canton, Ohio, 44718
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
University of Southern California Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Washington University School of Medicine
St Louis, Missouri, 63110
Germany4 sites
Universitätsklinikum Aachen
Aachen, North Rhine-Westphalia
Gemeinschaftspraxis Haematologie - Onkologie - Hauptstelle
Dresden, Saxony
Universitätsklinikum Carl Gustav Carus
Dresden, Saxony
Stauferklinikum Schwäbisch Gmünd
Mutlangen, 73557
Spain3 sites
Hospital Universitario de Gran Canaria Doctor Negrin
Las Palmas de Gran Canaria, LAS Palmas
Hospital Universitario Virgen de la Victoria
Málaga, 29010
Hospital Universitario de Salamanca
Salamanca, 37007
Poland2 sites
Szpital Wojewódzki w Opolu
Opole, 45-061
Dolnośląskie Centrum Transplantacji Komórkowych z Krajowym Bankiem Dawców Szpiku
Wroclaw, Lower Silesian Voivodeship
About this study
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
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.
- Conditions
- Polycythemia Vera
- Being tested
- KRT-232, Ruxolitinib
- Medical subject headings
- Polycythemia Vera
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KRT-232Drug
KRT-232, administered by mouth
RuxolitinibDrug
Ruxolitinib per approved prescribing label
| Study group | Role | What they receive |
|---|---|---|
| Part A Arm 1 | Experimental | KRT-232 120mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles) Receives: Drug: KRT-232 |
| Part A Arm 2 | Experimental | KRT-232 240mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles) Receives: Drug: KRT-232 |
| Part A Arm 3 | Experimental | KRT-232 120mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles) Receives: Drug: KRT-232 |
| Part B KRT-232 Arm | Experimental | Recommended KRT-232 dose and schedule from Part A Receives: Drug: KRT-232 |
| Part B Ruxolitinib Arm | Active comparator | Ruxolitinib per approved prescribing label Receives: Drug: Ruxolitinib |
| Part A Arm 4b | Experimental | KRT-232 240mg by mouth once daily for Days 1-5, off treatment for Days 6-28 (28-day cycles) Receives: Drug: KRT-232 |
| Part A Arm 2b | Experimental | KRT-232 240mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles) Receives: Drug: KRT-232 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 32 weeks
Secondary outcomes (4)
Duration of response after achieving both the absence of phlebotomy eligibility and reduction in spleen volume (for patients with splenomegaly)
Measured: 4 years
Duration of response after achieving phlebotomy independence
Measured: 4 years
Change from baseline of MPN-SAF TSS v2.0 patient-reported outcome
Measured: 32 weeks
Change from baseline of EORTC-QLQ-C30 patient-reported outcome
Measured: 32 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2018
- Study start15 Jan 2019
- Primary completionApr 2022 (estimated)
- Study completionOct 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Polycythemia VeraStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kartos Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03669965
- Sponsor's protocol ID
- KRT-232-102
- Status last verified
- Jul 2020
- First submitted
- 5 Sep 2018
- Last updated
- 31 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03669965
- Acronym / sponsor ID
- KRT-232-102
- Conditions
- Polycythemia Vera
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Kartos Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 15 Jan 2019 (actual)
- Primary completion
- Apr 2022 (estimated)
- Study completion
- Oct 2022 (estimated)
- First posted
- 13 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Part A Arm 1 | Experimental | Drug: KRT-232KRT-232 120mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles) |
| Part A Arm 2 | Experimental | Drug: KRT-232KRT-232 240mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles) |
| Part A Arm 3 | Experimental | Drug: KRT-232KRT-232 120mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles) |
| Part B KRT-232 Arm | Experimental | Drug: KRT-232Recommended KRT-232 dose and schedule from Part A |
| Part B Ruxolitinib Arm | Active comparator | Drug: RuxolitinibRuxolitinib per approved prescribing label |
| Part A Arm 4b | Experimental | Drug: KRT-232KRT-232 240mg by mouth once daily for Days 1-5, off treatment for Days 6-28 (28-day cycles) |
| Part A Arm 2b | Experimental | Drug: KRT-232KRT-232 240mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KRT-232KRT-232, administered by mouth | Drug | Part A Arm 1, Part A Arm 2, Part A Arm 2b, Part A Arm 3, Part A Arm 4b, Part B KRT-232 Arm |
| RuxolitinibRuxolitinib per approved prescribing label | Drug | Part B Ruxolitinib Arm |
Primary outcome
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
4 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
16 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing KRT-232 and Ruxolitinib in people with Polycythemia Vera, run by Kartos Therapeutics, Inc. at 16 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 31 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States, Germany, Spain, Poland, France and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients with splenomegaly achieving a response at Week 32 (time frame: 32 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2020.