A Phase 1 Study of PRT12396 in Participants With Select Myeloproliferative Neoplasms

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).

Study Overview

• Status: Recruiting
• Conditions: Post-Polycythemia Vera Myelofibrosis; Primary Myelofibrosis (PMF); Myelofibrosis (MF); Myeloproliferative Neoplasms (MPNs); Polycythemia Vera (PV); Post-Essential Thrombocythemia Myelofibrosis
• Intervention / Treatment: Drug: PRT12396

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.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Study Contact (Please Do Not Disclose Personal Information); Phone Number: See Email; Email: clinicaltrials@preludetx.com

Study Locations

• United States
  • Florida
    • Coral Springs, Florida, United States, 33065
      • Recruiting
      • BRCR Global - Coral Springs
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Recruiting
      • START Midwest, LLC
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Tristar BMT

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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 0-2
• 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)

Exclusion Criteria:

• 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.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PRT12396: MF; 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)	Drug: PRT12396; 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.
Experimental: PRT12396: PV; 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)	Drug: PRT12396; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose limiting toxicity (DLT) of PRT12396	Incidence of dose limiting toxicities, defined according to protocol-specified criteria	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	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	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	Through study completion, an average of 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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	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	Through study completion, an average of 2 years
Change from Baseline in Hemoglobin (MF)	Change from baseline in hemoglobin levels in MF participants	Through study completion, an average of 2 years
Change from Baseline in Platelet Count (MF)	Change from baseline in platelet count in MF participants	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	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	Through study completion, an average of 2 years
Maximum Observed Plasma Concentration (Cmax)	Maximum observed plasma concentration will be calculated using non-compartmental analysis	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	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	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	Cycle 1 Day 1
Steady State Trough Concentrations	Steady state trough concentrations will be calculated using non-compartmental analysis	Up to Cycle 4 Day 1 (each cycle is 4 weeks)
Clearance	Clearance will be calculated using non-compartmental analysis	Cycle 1 Day 1
Accumulation	Accumulation will be calculated using non-compartmental analysis	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.	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.	Through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: Prelude Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: February 26, 2026
• First Submitted That Met QC Criteria: March 9, 2026
• First Posted (Actual): March 13, 2026

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: JAK Inhibitor; 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; Myeloproliferative Neoplasms (MPN)
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Hematologic Diseases; Bone Marrow Diseases; Bone Marrow Neoplasms; Hematologic Neoplasms; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Polycythemia Vera; Primary Myelofibrosis
• Other Study ID Numbers: PRT12396-01; 2026-525484-40-00 (Ctis)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No