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

NCT07469891 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: PRT12396-012026-525484-40-00
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 5

Brief 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) 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

Primary Myelofibrosis (PMF); Polycythemia Vera (PV); Myelofibrosis (MF); Myeloproliferative Neoplasms (MPNs); Post-Polycythemia Vera Myelofibrosis; Post-Essential Thrombocythemia Myelofibrosis

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)

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (17)

• Hematologic Response Rate (PV)

  Through study completion, an average of 2 years

• Duration of Hematologic Response (PV)

  Through study completion, an average of 2 years

• Hematocrit Control Without Phlebotomy Requirements (PV)

  Through study completion, an average of 2 years

• Spleen Response (MF)

  Through study completion, an average of 2 years

• Change from Baseline in Hemoglobin (MF)

  Through study completion, an average of 2 years

Study Arms (2)

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)

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)

Drug: PRT12396

Interventions

PRT12396 DRUG

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.

PRT12396: MF; PRT12396: PV

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Prelude Therapeutics: lead

Study Sites (5)

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

RECRUITING

BRCR Global - Coral Springs

Coral Springs, Florida, 33065, United States

RECRUITING

START Midwest, LLC

Grand Rapids, Michigan, 49546, United States

RECRUITING

Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Trials Office

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

Tristar BMT

Nashville, Tennessee, 37203, United States

RECRUITING

MeSH Terms

Conditions

Polycythemia Vera; Primary Myelofibrosis; Myeloproliferative Disorders

Condition Hierarchy (Ancestors)

Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

Study Contact (Please Do Not Disclose Personal Information)

CONTACT

See Email; clinicaltrials@preludetx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2026
• First Posted: March 13, 2026
• Study Start: April 29, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028
• Last Updated: June 9, 2026

Record last verified: 2026-05

Locations

US (5)