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Purpose

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).

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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 Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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.

Recruiting Locations

START Midwest, LLC
Grand Rapids, Michigan 49546

More Details

Status
Recruiting
Sponsor
Prelude Therapeutics

Study Contact

Study Contact (Please Do Not Disclose Personal Information)
See Email
clinicaltrials@preludetx.com

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.