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

Official title

A Phase 1, Open-Label, Multi-Center, Safety and Efficacy Study of PRT12396 in Participants With Polycythemia Vera and Myelofibrosis

Overview

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).

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.

Interventions

• 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.

Primary outcome measures

• Dose limiting toxicity (DLT) of PRT12396 [Time frame: Through cycle 1 (4 weeks)]
• Incidence and severity of Adverse events [Time frame: Through study completion, an average of 2 years]
• Adverse Events Leading to Dose Modifications or Discontinuation [Time frame: Through study completion, an average of 2 years]
• Maximum tolerated dose (MTD) and Recommended Dose(s) for Expansion (RDE[s]) of PRT12396 [Time frame: Through study completion, an average of 2 years]

Secondary outcome measures (12)

• Hematologic Response Rate (PV) [Time frame: Through study completion, an average of 2 years]
• Duration of Hematologic Response (PV) [Time frame: Through study completion, an average of 2 years]
• Hematocrit Control Without Phlebotomy Requirements (PV) [Time frame: Through study completion, an average of 2 years]
• Spleen Response (MF) [Time frame: Through study completion, an average of 2 years]
• Change from Baseline in Hemoglobin (MF) [Time frame: Through study completion, an average of 2 years]
• Change from Baseline in Platelet Count (MF) [Time frame: Through study completion, an average of 2 years]
• Change from Baseline in Absolute Neutrophil Count (MF) [Time frame: Through study completion, an average of 2 years]
• Transfusion Independence (MF) [Time frame: Through study completion, an average of 2 years]
• Maximum Observed Plasma Concentration (Cmax) [Time frame: Up to Cycle 4 Day 1 (each cycle is 4 weeks)]
• Time To Maximum Concentration (Tmax) [Time frame: Up to Cycle 4 Day 1 (each cycle is 4 weeks)]
• Area under the plasma concentration versus time curve (AUC) [Time frame: Up to Cycle 4 Day 1 (each cycle is 4 weeks)]
• Terminal Elimination Half-life (T1/2) [Time frame: Cycle 1 Day 1]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 8 centers

• Colorado Blood Cancer Institute — Denver
• BRCR Global - Coral Springs — Coral Springs
• Moffitt Cancer Center — Tampa
• START Midwest, LLC — Grand Rapids
• Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Trials Office — Philadelphia
• Tennessee Oncology, PLLC - Investigational Drug Services — Nashville
• Tristar BMT — Nashville
• The University of Texas, MD Anderson Cancer Center — Houston

Identifiers

NCT: NCT07469891 · PRT12396-01 · 2026-525484-40-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗