Study to Evaluate Safety, Pharmacokinetic and Pharmacodynamic Dose Escalation and Expansion Study of PXS-5505 in Patients With Primary, Post-polycythemia Vera or Post-essential Thrombocythemia Myelofibrosis

NCT04676529 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: PXS5505-MF-101
• Study Type: interventional
• Target: 43
• Locations: 4 countries
• Sites: 23

Brief Summary

This study will be an open-label phase 1/2a study to evaluate the safety and tolerability of PXS-5505 in patients with primary, postpolycythemia vera (PV) or post-essential thrombocythemia (ET) myelofibrosis.

Conditions

Myelofibrosis

Keywords

Thrombocythemia myelofibrosis; PXS-5505; Post polycythemia vera myelofibrosis

Outcome Measures

Primary Outcomes (1)

• Number of subjects with serious and non-serious adverse events

  Safety and tolerability of PXS-5505 in patients with myelofibrosis will be assessed

  Day 0 to follow-up visit (28 days -1 to +7days post-Tx discontinuation [dose escalation phase]; Day 0 to 28 days ± 3 days post-Tx discontinuation [cohort expansion phase]); Day 0 to follow-up visit (28 days ± 3 days post-Tx discontinuation [add-on phase]

Secondary Outcomes (8)

• Maximum plasma concentration (C1hr=Cmax)

  Day 0, week 1 and week 4 (dose escalation), and Day 0, week 4, 12 and 24 (cohort expansion and add-on phase), and week 52 during add-on phase only

• Minimum plasma concentration (Cmin)

  Day 0, week 1 and week 4 (dose escalation), and Day 0, week 4, 12 and 24 (cohort expansion and add-on phase), and week 52 during add-on phase only

• Lysyl oxidase and lysyl oxidase-like 2 inhibition in plasma

  Day 0, week 1 and week 4 dose escalation, and at week 0, 4, 12, 24 (cohort expansion and add-on phase), and week 52 during add-on phase only

• Change in bone marrow (BM) fibrosis

  Day 0, Week 12 and Week 24 (cohort expansion and add-on phase), and week 52 during add-on phase only

• Response rate

  At week 12 and week 24 (cohort expansion and add-on phase), weeks 38 and 52 during add-on phase only

Study Arms (5)

PXS-5505, Dose Level 1, Escalation Phase (Cohort A)

EXPERIMENTAL

Patients will receive PXS-5505 dose level 1, twice daily for a period of 4 weeks.

Drug: PXS-5505

PXS-5505, Dose Level 2, Escalation Phase (Cohort B)

EXPERIMENTAL

Patients will receive PXS-5505 dose level 2, twice daily for a period of 4 weeks.

Drug: PXS-5505

PXS-5505, Dose Level 3, Escalation Phase (Cohort C)

EXPERIMENTAL

Patients will receive PXS-5505 dose level 3, twice daily for a period of 4 weeks.

Drug: PXS-5505

PXS-5505, Expansion Phase

EXPERIMENTAL

All patients will receive PXS-5505 at the selected twice daily dose for a period of 24 weeks, or until progressive disease, unacceptable toxicity, dose-limiting toxicity or withdrawal of consent.

Drug: PXS-5505

PXS-5505, Add-on Phase

EXPERIMENTAL

Patients already receiving a stable dose of ruxolitinib for at least 12 weeks, will receive PXS-5505 (the dose used in the cohort expansion phase) on top of their ruxolitinib dose for up to 52 weeks or until progressive disease, unacceptable toxicity, dose-limiting toxicity, or withdrawal of consent.

Drug: PXS-5505

Interventions

PXS-5505 DRUG

PXS-5505 is a hard capsule (size 0) with the additional excipients mannitol and magnesium stearate.

PXS-5505, Add-on Phase; PXS-5505, Dose Level 1, Escalation Phase (Cohort A); PXS-5505, Dose Level 2, Escalation Phase (Cohort B); PXS-5505, Dose Level 3, Escalation Phase (Cohort C); PXS-5505, Expansion Phase

Eligibility Criteria

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

You may qualify if:

• Have a pathologically confirmed established diagnosis of primary myelofibrosis or post-essential thrombocythemia/polycythemia vera myelofibrosis as per the World Health Organization 2016 diagnostic criteria (must include at least Grade 2 marrow fibrosis)
• Patients who are not eligible for stem cell transplantation
• a) Dose escalation / Cohort expansion phase only: Patients not currently on ruxolitinib or fedratinib (where available) treatment due to ineligibility, or previously treated patients who have been discontinued for at least 2 weeks prior to first dose of study drug due to any of the following criteria:
• Ineligible: Platelets \<50 x 10\^9/L
• Intolerant: Development of red blood cell transfusion dependence of at least two units/month for 2 months OR ≥Grade 3 adverse events of thrombocytopenia, anemia, hematoma, and/or hemorrhage while on treatment with ruxolitinib or fedratinib for at least 28 days
• Refractory: \< 10% spleen volume reduction by MRI or CT, or \< 30% decrease from baseline in spleen volume by palpation after at least 3 months treatment with ruxolitinib or fedratinib
• Relapsed: Regrowth to \< 10% spleen volume reduction by MRI or CT, or \< 30% decrease from baseline in spleen volume by palpation, following an initial response to ruxolitinib or fedratinib and after at least 3 months treatment
• b) Add-on phase only: Are being treated with ruxolitinib for at least 12 weeks prior to first administration of study treatment. The patient must be on a stable dose (no dose adjustments) of ruxolitinib for ≥ 8 weeks prior to study treatment and have not achieved complete remission (CR) by International Working Group (IWG) criteria.
• Have intermediate -2, or high-risk disease according to the International Working Group prognostic scoring system (DIPSS);
• a) Dose escalation / Cohort expansion phase only: Have symptomatic disease according to the MFSAF v4.0; Symptomatic disease is defined as a score of at least one in at least two items of the MFSAF v4.0;
• b) Add-on phase only: have a score of ≥ 10 on the MFSAF v4.0;
• Have symptomatic disease according to the MFSAF v4.0;
• Life expectancy of six months or greater;
• Must have adequate organ function as demonstrated by the following (within last 2 weeks):
• Alanine aminotransferase and/or aspartate aminotransferase ≤ 2.5x upper limit of normal (ULN), or ≤ 4 x ULN (if upon judgment of the treating physician, it is believed to be due to extramedullary hematopoiesis \[EMH\] related to MF);

You may not qualify if:

• Greater than (\>) 10% blasts in peripheral blood (determined within last two weeks);
• Prior splenectomy, or planning to undergo splenectomy, or splenic irradiation within 3 months prior to the first dose of study treatment
• Any serious medical condition or psychiatric illness that would prevent (as judged by the treating physician) the subject from signing the informed consent form or any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
• Known history of human immunodeficiency virus, active hepatitis C, or active hepatitis B
• History or presence of any form of cancer within the three years prior to enrolment, with the exception of excised basal cell or squamous cell carcinoma of the skin, or cervical carcinoma in situ or breast carcinoma in situ that has been excised or resected completely and is without evidence of local recurrence or metastasis
• Participation in an investigational drug or device trial within two weeks prior to study Day 1 or within five times the half-life of the investigational agent in the other clinical study, if known
• Use of any cytotoxic chemotherapeutic agents, including hydroxyurea, corticosteroids (prednisone ≤ 10 mg/day or corticosteroid equivalent is allowed), or immune modulators (e.g., thalidomide) within two weeks and interferon use within four weeks prior to study Day 1
• Symptomatic congestive heart failure (New York Heart Association Classification Class II), unstable angina, or unstable cardiac arrhythmia requiring medication
• Pregnancy
• History of surgery within two weeks prior to enrolment or anticipated surgery during the study period or two weeks post-study
• History of aneurysm
• Any other condition that might reduce the chance of obtaining data required by the protocol or that might compromise the ability to give truly informed consent.

Sponsors & Collaborators

• Syntara: lead

Study Sites (23)

Comprehensive Cancer Center (UAB CCC)

Birmingham, Alabama, 98374, United States

Location

Novant Health Cancer Institute

Winston-Salem, North Carolina, 27103, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

Ashford Cancer Centre Research

Adelaide, South Australia, 5037, Australia

Location

St Vincent's Hospital Melbourne

Fitzroy, Victoria, 3065, Australia

Location

One Clinical Research

Perth, Western Australia, 6009, Australia

Location

The Perth Blood Institute

West Perth, Western Australia, 6005, Australia

Location

Inje University Busan Paik Hospital - Internal Medicine

Busan, Busan Gwang'yeogsi [Pusan-Kwan, 47392, South Korea

Location

Keimyung University Dongsan Hospital

Daegu, Daegu Gwang'yeogsi [Taegu-Kwangyokshi], 42601, South Korea

Location

Gachon University Gil Hospital

Incheon, Incheon Gwang'yeogsi [Inch'n-K, 21565, South Korea

Location

National Cancer Center (Seoul Metro; northern)

Gyeonggi-do, 10408, South Korea

Location

Seoul National University Hospital - Bundang

Gyeonggi-do, 13620, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital, Yonsei University Health System- Haemat

Seoul, 03711, South Korea

Location

Asan Medical Centre

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, 06591, South Korea

Location

Chang Gung Medical Foundation - ChiaYi Chang Gung Memorial Hospital - Hematology and Oncology

Chiayi City, Chiayi, 613, Taiwan

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 807, Taiwan

Location

China Medical University Hospital - Internal Medicine - Taichung

Taichung, 40447, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 70403, Taiwan

Location

National Taiwan University Hospital - Hematology And Oncology

Taipei, 100, Taiwan

Location

Related Publications (1)

• Vachhani P, Tan P, Watson AM, Wu SJ, Baker R, Cheung S, Lee SE, Chen CC, Chen TY, Hsiao HH, Lee JH, Masarova L, Tan SY, Baskar J, Charlton B, Findlay A, Hamprecht D, Jarolimek W, Leadbetter J, Miller J, Morgan K, Zahoor A, Hobbs G. A phase I/IIa trial of PXS-5505, a novel pan-lysyl oxidase inhibitor, in advanced myelofibrosis. Haematologica. 2025 Oct 1;110(10):2376-2387. doi: 10.3324/haematol.2024.287231. Epub 2025 Apr 17.

  PMID: 40241543 DERIVED

MeSH Terms

Conditions

Primary Myelofibrosis

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Jana Baskar, MBBS MMedSc MBA

  Syntara

  STUDY DIRECTOR

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: December 8, 2020
• First Posted: December 21, 2020
• Study Start: February 18, 2021
• Primary Completion: July 9, 2025
• Study Completion: July 9, 2025
• Last Updated: August 24, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

KR (10); US (3); TW (5); AU (5)