Polycythemia Vera (PV)Phase 1NCT07469891
A Phase 1 Study of PRT12396 in Participants With Select Myeloproliferative Neoplasms
A Phase 1 study testing PRT12396 in people with Polycythemia Vera (PV) and Myelofibrosis (MF), run by Prelude Therapeutics Incorporated at 18 sites in 4 countries.
Trial summary
This is a first-in-human, open-label, multi-center Phase 1 study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of PRT12396 in participants with high-risk polycythemia vera (PV) and myelofibrosis (MF), and to determine the maximum tolerated dose (MTD) and recommended dose(s)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Polycythemia Vera (PV), Myelofibrosis (MF), Myeloproliferative Neoplasms (MPNs)
- What is being tested?
- PRT12396
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 18 sitesin 4 countries
- Study dates
- 29 Apr 2026to Apr 2028
- Phase
- Phase 1
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
- Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations (including contraception requirements), and other study procedures.
- Confirmed diagnosis of PV or MF according to WHO 2016 or revised ICC/WHO 2022 criteria
- Documented presence of a JAK2 V617 mutation
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Estimate life expectancy of ≥12 weeks per investigator assessment.
- Negative serum or urine pregnancy test and agree to use contraception or maintain true abstinence.
- Adequate organ function and bone marrow reserves (hematology, renal, and hepatic)
Who cannot join
- History of another malignancy within 3 years prior to enrollment, except for malignancy considered cured with low risk of recurrence.
- Clinically significant anemia due to nutritional deficiency or hemolytic disorders.
- Active or uncontrolled infection requiring systemic therapy or hospitalization.
- Any other medical or psychiatric conditions that, in the Investigator's judgment, would increase risk or interfere with study participation or interpretation of results.
- Clinically significant or uncontrolled medical conditions, including active infection or cardiovascular disease, that would increase risk or interfere with study participation.
- Unresolved toxicity Grade >1 from prior anticancer therapy, except for alopecia or peripheral neuropathy Grade ≤2.
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- Pregnancy or breastfeeding
- Known sensitivity or contraindication to any component of study, or the excipients of study treatment.
- Prior systemic therapy for PV or MF, prior or planned allogeneic hematopoietic stem-cell transplantation, recent major surgery, prior splenectomy or prior splenic irradiation, or use of hematopoietic growth factors within protocol-defined washout periods.
- Use of strong or moderate cytochrome P450 (CYP) 3A4 inhibitor or inducer, sensitive CYP3A substrates with narrow therapeutic range, or acid-reducing agents that cannot be discontinued prior to study treatment.
- Participation in another interventional clinical study.
Trial locations and contacts
18 sites in 4 countries. Contact the study team or a site near you to ask about taking part.
Study Contact (Please Do Not Disclose Personal Information) contact
18 sites in 4 countries
United States9 sites, 9 recruiting
- Recruiting
BRCR Global - Coral Springs
Coral Springs, Florida, 33065
- Recruiting
Colorado Blood Cancer Institute
Denver, Colorado, 80218
- Recruiting
START Midwest, LLC
Grand Rapids, Michigan, 49546
- Recruiting
The University of Texas, MD Anderson Cancer Center
Houston, Texas, 77030
- Recruiting
UCLA Ronald Reagan Medical Center
Los Angeles, California, 90095
- Recruiting
Tennessee Oncology, PLLC - Investigational Drug Services
Nashville, Tennessee, 37203
- Recruiting
Tristar BMT
Nashville, Tennessee, 37203
- Recruiting
Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Trials Office
Philadelphia, Pennsylvania, 19107
- Recruiting
Moffitt Cancer Center
Tampa, Florida, 33612
Spain4 sites, 4 recruiting
- Recruiting
Hospital Clinic de Barcelona
Barcelona, 08036
- Recruiting
Hospital Universitario Ramon y Cajal
Madrid, 28034
- Recruiting
Hospital Universitario 12 de Octubre
Madrid, 28041
- Recruiting
Hospital Clínico Universitario de Valencia
Valencia, 46010
Australia3 sites, 3 recruiting
- Recruiting
Royal Adelaide Hospital
Adelaide, South Australia, 5000
- Recruiting
Monash Health, Monash Medical Centre
Clayton, Victoria, 3168
- Recruiting
One Clinical Research
Nedlands, Western Australia, 6009
France2 sites, 2 recruiting
- Recruiting
Saint-Louis Hospital
Paris, 75010
- Recruiting
Oncopole Claudius Regaud
Toulouse, 31059
About this study
Official title: A Phase 1, Open-Label, Multi-Center, Safety and Efficacy Study of PRT12396 in Participants With Polycythemia Vera and Myelofibrosis
This is a first-in-human, open-label, multi-center Phase 1 study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of PRT12396 in participants with high-risk polycythemia vera (PV) and myelofibrosis (MF), and to determine the maximum tolerated dose (MTD) and recommended dose(s) for expansion (RDE[s]). The study consists of a dose-escalation phase followed by a dose-expansion phase to further evaluate selected dose level(s).
Read the detailed description
This first-in-human, open-label, multi-center Phase 1 study is designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of PRT12396 in participants with high-risk polycythemia vera (PV) and myelofibrosis (MF). Eligible MF populations include participants with intermediate-1, intermediate-2, or high-risk primary MF, as well as post-polycythemia vera MF or post-essential thrombocythemia MF, with evidence of disease burden based on splenomegaly.
The study is conducted in two parts:
Part 1 (dose escalation) evaluates escalating oral doses of PRT12396 to evaluate safety and tolerability and to determine the maximum tolerated dose (MTD) and recommended dose(s) for expansion (RDE[s]).
Part 2 (dose expansion) enrolls additional participants at selected dose level(s) to further characterize the safety, tolerability, pharmacokinetics, and preliminary efficacy of PRT12396 in the PV and MF populations.
Approximately up to 100 participants are planned for enrollment across both parts of the study.
- Conditions
- Polycythemia Vera (PV), Myelofibrosis (MF), Myeloproliferative Neoplasms (MPNs), Post-Polycythemia Vera Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis, Primary Myelofibrosis (PMF)
- Being tested
- PRT12396
- Keywords
- High-Risk Polycythemia Vera (PV), Intermediate-1 or Intermediate-2 Risk Primary MF, High-Risk Primary MF, Post-Polycythemia Vera MF, Post-Essential Thrombocythemia MF, PRT12396, JAK Inhibitor, Myeloproliferative Neoplasms (MPN)
- Medical subject headings
- Polycythemia Vera, Primary Myelofibrosis, Myeloproliferative Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PRT12396Drug
PRT12396 is an investigational oral capsule administered twice daily at the assigned dose level or RDE. Capsules are swallowed whole with water and may be taken one hour before or two hours after meals.
| Study group | Role | What they receive |
|---|---|---|
| PRT12396: MF | Experimental | Participants with myelofibrosis receive PRT12396, an investigational oral capsule, administered twice daily. The study includes a dose-escalation followed by dose-expansion at the recommended dose for expansion (RDE) Receives: Drug: PRT12396 |
| PRT12396: PV | Experimental | Participants with polycythemia vera receive PRT12396, an investigational oral capsule, administered twice daily. The study includes a dose-escalation followed by dose-expansion at the recommended dose for expansion (RDE) Receives: Drug: PRT12396 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicity (DLT) of PRT12396
Incidence of dose limiting toxicities, defined according to protocol-specified criteria
Measured: Through cycle 1 (4 weeks)
Incidence and severity of Adverse events
Incidence and severity of treatment-emergent adverse events (AEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 6.0
Measured: Through study completion, an average of 2 years
Adverse Events Leading to Dose Modifications or Discontinuation
Incidence of AEs leading to dose reductions, dose interruptions, treatment discontinuations, and clinically significant laboratory abnormalities
Measured: Through study completion, an average of 2 years
Maximum tolerated dose (MTD) and Recommended Dose(s) for Expansion (RDE[s]) of PRT12396
Determination of the maximum tolerated dose (MTD) and recommended dose(s) for expansion (RDE[s]) based on evaluation of DLTs, safety, and tolerability data
Measured: Through study completion, an average of 2 years
Secondary outcomes (17)
Hematologic Response Rate (PV)
Proportion of participants with polycythemia vera (PV) achieving best overall hematologic response (complete hematologic response or partial hematologic response) from the overall response assessments by Investigator
Measured: Through study completion, an average of 2 years
Duration of Hematologic Response (PV)
Duration of hematologic response in PV participants, defined as the time from first documented response (best overall hematologic response) to disease progression or death, whichever comes first
Measured: Through study completion, an average of 2 years
Hematocrit Control Without Phlebotomy Requirements (PV)
Proportion of PV participants achieving and maintaining hematocrit control without phlebotomy, time to first phlebotomy, and frequency of phlebotomy
Measured: Through study completion, an average of 2 years
Spleen Response (MF)
Assessment of spleen response including proportion achieving protocol-specified reduction in spleen volume, time to spleen response, duration of spleen response, and reduction in palpable spleen length
Measured: Through study completion, an average of 2 years
Change from Baseline in Hemoglobin (MF)
Change from baseline in hemoglobin levels in MF participants
Measured: Through study completion, an average of 2 years
Change from Baseline in Platelet Count (MF)
Change from baseline in platelet count in MF participants
Measured: Through study completion, an average of 2 years
Change from Baseline in Absolute Neutrophil Count (MF)
Change from baseline in absolute neutrophil count in MF participants
Measured: Through study completion, an average of 2 years
Transfusion Independence (MF)
Proportion achieving transfusion independence and duration of transfusion independence as defined by protocol criteria
Measured: Through study completion, an average of 2 years
Maximum Observed Plasma Concentration (Cmax)
Maximum observed plasma concentration will be calculated using non-compartmental analysis
Measured: Up to Cycle 4 Day 1 (each cycle is 4 weeks)
Time To Maximum Concentration (Tmax)
Time to maximum concentration will be calculated using non-compartmental analysis
Measured: Up to Cycle 4 Day 1 (each cycle is 4 weeks)
Area under the plasma concentration versus time curve (AUC)
Area under the plasma concentration-time curve will be calculated using non-compartmental analysis
Measured: Up to Cycle 4 Day 1 (each cycle is 4 weeks)
Terminal Elimination Half-life (T1/2)
Terminal elimination half-life will be calculated using non-compartmental analysis
Measured: Cycle 1 Day 1
Steady State Trough Concentrations
Steady state trough concentrations will be calculated using non-compartmental analysis
Measured: Up to Cycle 4 Day 1 (each cycle is 4 weeks)
Clearance
Clearance will be calculated using non-compartmental analysis
Measured: Cycle 1 Day 1
Accumulation
Accumulation will be calculated using non-compartmental analysis
Measured: Up to Cycle 4 Day 1 (each cycle is 4 weeks)
Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS)
Patient-reported outcomes assessed using the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS), evaluated as change from baseline at protocol-specified time points. The MPN SAF TSS is a validated questionnaire in which individual symptoms are scored using a numeric rating scale ranging from 0 to 10, with 0 indicating no symptoms and 10 indicating the worst imaginable symptoms; higher scores indicate greater symptom severity.
Measured: Through study completion, an average of 2 years
Patient Global Impression of Change (PGI-C)
Participant reported outcomes assessed using the Patient Global Impression of Change (PGI-C), evaluated at protocol-specified time points. The PGI C is a global assessment scale in which participants rate their overall change in condition since baseline using a 7 point ordinal scale ranging from "very much improved" to "very much worse," with lower scores indicating improvement and higher scores indicating worsening of symptoms.
Measured: Through study completion, an average of 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2026
- Study start29 Apr 2026
- Primary completionApr 2028 (estimated)
- Study completionApr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Polycythemia Vera (PV)Studies 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Prelude Therapeutics Incorporated
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07469891
- Sponsor's protocol ID
- PRT12396-01
- Other IDs
- 2026-525484-40-00
- Status last verified
- Sep 2026
- First submitted
- 26 Feb 2026
- Last updated
- 1 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No