Evaluating Safety ,Tolerability, Pharmacokinetic,Efficacy of WJ01024 or WJ01024 Combined With Ruxolitinib in Patients With Myelofibrosis

A Phase I Clinical Study Evaluating the Safety and Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of Oral Administration of WJ01024 as a Monotherapy and in Combination With Ruxolitinib in Patients With Myelofibrosis

This is a Phase I clinical study to evaluate the safety and tolerability, pharmacokinetic characteristics and preliminary efficacy of oral WJ01024 administered as monotherapy and in combination with ruxolitinib in patients with myelofibrosis（MF）. The study will be conducted in two phases: Phase IA and Phase IB.

Phase IA is a dose-escalation and dose-expansion study of WJ01024 monotherapy in patients with MF after failure of JAK inhibitor (JAKi) therapy (relapsed/refractory/intolerant). Phase IB is a dose-escalation and dose-expansion study of WJ01024 in combination with ruxolitinib in JAKi-naïve patients with intermediate- or high-risk MF.

Study Overview

• Status: Recruiting
• Conditions: MF With Splenomegaly
• Intervention / Treatment: Drug: WJ01024 tablet

Detailed Description

Phase IA is a dose-escalation and dose-expansion study of WJ01024 monotherapy in patients with MF after failure of JAK inhibitor (JAKi) therapy (relapsed/refractory/intolerant).Dose escalation is carried out by combining accelerated titration and the traditional 3+3 design. During the accelerated titration phase, if no dose-limiting toxicity (DLT) and no ≥2 episodes of grade ≥2 treatment-related adverse events (TRAEs) occur within the first cycle (DLT observation period), no further subjects are enrolled at that dose level, and the study proceeds to the traditional 3+3 phase starting with the 60 mg group. At present, it is expected that the dose will be increased in four groups . If the researchers elects to explore intermediate doses or higher doses during the trial, adjustments will be made based on the actual situation. It is planned to expand the dosage by two groups. The final expanded dosage will be determined based on emerging safety and efficacy data. Dose escalation is stratified by background therapy (with vs. without background medication). Phase IB involves dose escalation and dose expansion studies of WJ01024 combined with ruxolitinib. Phase IB is planned to be conducted in JAKi-naïve patients with intermediate- or high-risk MF. Initiation of Phase IB requires that the group in Phase IA has completed the DLT observation period. Two combination dose groups are planned. Intermediate or higher doses may be explored at the investigator's discretion.Two combination dose levels are planned for expansion ;final expansion dose(s) will be determined based on emerging safety and efficacy data.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Shuai Guo; Phone Number: 15902401702; Email: sguo@wigenbio.com

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Recruiting
      • Henan Cancer Hospital
      • Contact: Zhou Hu, PhD.; Phone Number: 13939068863; Email: papertigerhu@163.com
      • Principal Investigator: Zhou Hu, Ph.D.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. The subjects voluntarily participated in this study after obtaining full informed consent and signed the informed consent form.
2. Age ≥18 years old, gender not limited;
3. Patients diagnosed with primary myelofibrosis (PMF) according to the 2016 World Health Organization (WHO) criteria, or patients diagnosed with post-essential thrombocythemia MF (PET-MF) or post-polycythemia vera MF (PPV-MF) according to International Working Group for Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria;
4. Patients evaluated as intermediate-1, intermediate-2, or high-risk according to the International Prognostic System (DIPSS) scoring system;;
5. Expected life expectancy is ≥ 24 weeks;
6. Eastern Cooperative Oncology Group (ECOG) score of 0-2 ;
7. No planned for stem cell transplantation in the near future.
8. Splenomegaly: Palpation of the spleen margin reaches or exceeds at least 5cm below the costal margin (the distance from the costal margin to the farthest point of the spleen protrusion), or spleen volume ≥450cm ³ by CT or MRI.

9. Adequate hematological and organ function within 7 days before the first administration of the study drug (no RBC transfusion, growth factors, colony-stimulating factors, platelet-generating factors ,or platelet transfusion within 14 days before the testing) :

   • Absolute neutrophil count (ANC) ≥1.5×109/L;
   • Platelet count ≥75×109/L(Phase IA); Platelet count ≥100×109/L(Phase IB); Hemoglobin ≥ 8.0g /dL; Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0× upper limit of normal (ULN); Total bilirubin ≤1.5×ULN; Creatinine ≤1.5×ULN.
10. For women of childbearing age, within 7 days before the first administration, if the serum pregnancy test is confirmed to be negative and they agree to use effective contraceptive measures during the study drug period and within 90 days after the last administration. For male subjects whose sexual partners are women of childbearing age, they must agree to take effective contraceptive measures during the use of the study drug and within 90 days after the last administration.

Exclusion Criteria:

• Peripheral blood blasts >5% or Bone marrow blasts >10%.
• Previous treatment with XPO1 inhibitors.
• Unable to cooperate with or unable to perform MRI or CT scans as deemed necessary by sponsor and investigator
• Treatment with strong CYP3A inhibitors or inducers within 14 days prior to initial administration"

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: WJ01024 tablet	Drug: WJ01024 tablet; 5-20mg BID (dosage per investigator judgement)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DLT	Incidence of DLT	12 months
AE	incidence and severity of adverse events(AEs) and serious adverse events(SAEs),as well as abnormal changes in clinical significance laboratory tests and other examinations	4 years
MTD	Evaluate the Maximum tolerated dose	12 months
RP2D	Evaluate the recommended dose for phase II	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK) Parameter	The blood concentration of WJ01024	1.5 years
SVR35	Percentage of subjects with spleen volume reduction of ≥35% (SVR35)	4 years
Score in MPN-SAF-TSS	Percentage reduction in Total Symptom Score(TSS) and proportion of subjects achieving ≥50% reduction (TSS50) assessed by Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS)	4 years
incidence and severity of adverse events and serious adverse events	incidence and severity of adverse events nd serious adverse events,as well as abnormal changes in clinical significance laboratory tests and other examinations	4 years
ORR：CR + PR + clinical improvement	Overall response rate (ORR, CR + PR + clinical improvement) as determined by the investigator according to IWG-MRT criteria	4 years
LFS	Leukemia-free survival (LFS) as assessed by the investigator	4 years
PFS	Progression free survival (PFS) as assessed by the investigator	4 years
OS	OS	4 years
LDH	Evaluation of changes in serum LDH levels	4 years

Collaborators and Investigators

• Sponsor: Henan Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2023
• Primary Completion (Estimated): September 26, 2026
• Study Completion (Estimated): November 21, 2027

Study Registration Dates

• First Submitted: August 25, 2026
• First Submitted That Met QC Criteria: September 1, 2026
• First Posted (Actual): September 3, 2026

Study Record Updates

• Last Update Posted (Actual): September 3, 2026
• Last Update Submitted That Met QC Criteria: September 1, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: JS110-002-I（T）

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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