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MyelofibrosisPhase 1/2NCT04676529

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

A Phase 1/2 study testing PXS-5505 in people with Myelofibrosis and Primary Myelofibrosis (PMF), run by Syntara at 23 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
PXS-5505
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
43 participants
Where
23 sitesin 4 countries
Study dates
18 Feb 2021to 9 Jul 2025
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 20Show fewer
  • 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;
  • 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);
  • Direct bilirubin ≤ 1.5 x ULN; or ≤ 2 x ULN (if upon judgment of the treating physician, it is believed to be due to EMH related to MF);
  • Estimated glomerular filtration rate (eGFR) > 50 mL/min
  • Eastern Cooperative Oncology Group performance status ≤ 2;
  • Men must agree to using one medically approved contraceptive measure and have their partners agree to an additional barrier method of contraception for the duration of the study and for 90 days after the last administration of study drug; women of childbearing potential must use effective contraception
  • Cohort Expansion and Add-on Phase only: A bone marrow biopsy must have been performed within 3 months prior to Day 1 treatment to establish the baseline fibrosis score or within 6 months of the re-initiation of treatment with PXS-5505 if subject participated in dose escalation phase of the trial

Who cannot join

  • 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
Show all 12Show fewer
  • 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.

Trial locations and contacts

23 sites in 4 countries.

23 sites in 4 countries

South Korea10 sites

  • Inje University Busan Paik Hospital - Internal Medicine

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

  • Keimyung University Dongsan Hospital

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

  • National Cancer Center (Seoul Metro; northern)

    Gyeonggi-do, 10408

  • Seoul National University Hospital - Bundang

    Gyeonggi-do, 13620

  • Gachon University Gil Hospital

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

  • Seoul National University Hospital

    Seoul, 03080

  • Severance Hospital, Yonsei University Health System- Haemat

    Seoul, 03711

  • Asan Medical Centre

    Seoul, 05505

  • Samsung Medical Center

    Seoul, 06351

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

    Seoul, 06591

Other trials in South Korea

Australia5 sites

  • Ashford Cancer Centre Research

    Adelaide, South Australia, 5037

  • St Vincent's Hospital Melbourne

    Fitzroy, Victoria, 3065

  • Liverpool Hospital

    Liverpool, New South Wales, 2170

  • One Clinical Research

    Perth, Western Australia, 6009

  • The Perth Blood Institute

    West Perth, Western Australia, 6005

Other trials in Australia

Taiwan5 sites

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

    Chiayi City, Chiayi, 613

  • Kaohsiung Medical University Chung-Ho Memorial Hospital

    Kaohsiung City, 807

  • China Medical University Hospital - Internal Medicine - Taichung

    Taichung, 40447

  • National Cheng Kung University Hospital

    Tainan, 70403

  • National Taiwan University Hospital - Hematology And Oncology

    Taipei, 100

Other trials in Taiwan

United States3 sites

  • Comprehensive Cancer Center (UAB CCC)

    Birmingham, Alabama, 98374

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Novant Health Cancer Institute

    Winston-Salem, North Carolina, 27103

Other trials in United States

About this study

Official title: A Phase 1/2a Study to Evaluate Safety, Pharmacokinetic and Pharmacodynamic Dose Escalation and Expansion Study of PXS-5505 in Patients With Primary, Postpolycythemia Vera or Post-essential Thrombocythemia Myelofibrosis

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.

Read the detailed description

The study consists of three phases: a dose escalation phase, a cohort expansion phase, and an add-on phase.

The dose escalation phase will follow a 3+3 design with a starting dose of 100 mg twice daily, and a treatment duration of 4 weeks. Patients will be able to participate in more than one dose level.

During the cohort expansion phase, up to 24 patients will be treated at the dose determined appropriate based on safety, pharmacokinetic and pharmacodynamic results from the dose escalation phase, for a period of up to 6 months. Patients from the dose escalation phase will be able to participate in the cohort expansion phase.

In the add-on phase PXS-5505 will be given to patients, already receiving a stable dose of ruxolitinib, for a period of 12 months. Up to 15 patients will enrol in the add-on phase in order to obtain 12 patients with at least 1 month's exposure to PXS-5505 on top of ruxolitinib.

Note: The decision to include an add-on phase, where PXS-5505 is to be given on top of a stable ruxolitinib dose, was taken following a review of the data (safety, PK and PD) from the cohort expansion phase.

There will be no washout period between dose escalation and dose expansion cohorts.

Being tested
PXS-5505
Keywords
Thrombocythemia myelofibrosis, PXS-5505, Post polycythemia vera myelofibrosis, amsulostat
Medical subject headings
Primary Myelofibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PXS-5505Drug

    Also called amsulostat

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

Study groups in NCT04676529
Study groupRoleWhat they receive
PXS-5505, Dose Level 1, Escalation Phase (Cohort A)ExperimentalPatients will receive PXS-5505 dose level 1, twice daily for a period of 4 weeks.
Receives: Drug: PXS-5505
PXS-5505, Dose Level 2, Escalation Phase (Cohort B)ExperimentalPatients will receive PXS-5505 dose level 2, twice daily for a period of 4 weeks.
Receives: Drug: PXS-5505
PXS-5505, Dose Level 3, Escalation Phase (Cohort C)ExperimentalPatients will receive PXS-5505 dose level 3, twice daily for a period of 4 weeks.
Receives: Drug: PXS-5505
PXS-5505, Expansion PhaseExperimentalAll 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.
Receives: Drug: PXS-5505
PXS-5505, Add-on PhaseExperimentalPatients 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.
Receives: Drug: PXS-5505

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Subjects With Serious and Non-serious Adverse Events

    Safety and tolerability of PXS-5505 in patients with myelofibrosis will be assessed. More details on the types of AEs can be found in the safety results section.

    Measured: Day 0 to follow-up visit (28 -1/+7days post-Tx end) after up to 4wks Tx [escalation phase]; Day 0 to follow-up visit (28±3days post-Tx end) after up to 24wks Tx [expansion]); Day 0 to follow-up visit (28± 3days post-Tx end) after up to 52wks Tx [add-on].

Secondary outcomes (12)

  1. Maximum Plasma Concentration (Cmax)

    Pharmacokinetic parameters of PXS-5505 in patients with myelofibrosis. Cmax was taken to be the concentration at 1 hour post-dose.

    Measured: 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

  2. Minimum Plasma Concentration (Cmin)

    Pharmacokinetic parameters of PXS-5505 in patients with myelofibrosis will be assessed. Cmin was the concentration pre-dose at each visit.

    Measured: 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

  3. Lysyl Oxidase and Lysyl Oxidase-like 2 Inhibition in Plasma

    Pharmacodynamic parameters of PXS-5505 in patients with myelofibrosis. LOX and LOXL2 inhibition expressed as a percentage of the pre-dose activity on Day 0.

    Measured: 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

  4. Change in Bone Marrow (BM) Fibrosis - Reticulin

    Change in bone marrow reticulin fibrosis assessed according to European Consensus on grading of bone marrow fibrosis, centrally assessed.

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

  5. Change in Bone Marrow (BM) Fibrosis - Collagen

    Change in bone marrow collagen fibrosis, assessed according to European Consensus on grading of bone marrow fibrosis via central review

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

  6. IWG-MRT Response Rate, Investigator Assessment

    Response rates as assessed by the investigator based on International Working Group (IWG)-Myeloproliferative Neoplasms Research and Treatment criteria in patients with myelofibrosis administered PXS-5505

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

  7. Changes in Spleen Volume

    Changes in spleen volume, as measured by computed tomography (CT) or magnetic resonance imaging (MRI) scan, in patients with myelofibrosis administered PXS-5505

    Measured: Day 0, week 12, and week 24 (cohort expansion and add-on phase), weeks 38 and 52 during add-on phase only

  8. Changes in Spleen Volume - Achievement of SVR25

    Achievement of a reduction of 25% from baseline in the spleen volume in patients with myelofibrosis and enlarged spleen administered PXS-5505

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

  9. Changes in Spleen Volume - Achievement of SVR35

    Achievement of a reduction of 35% from baseline in the spleen volume in patients with myelofibrosis and an enlarged spleen administered PXS-5505

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

  10. Changes in Myelofibrosis Related Symptoms - Achievement of TSS50

    Achievement of a reduction of 50% from baseline in the Total Symptom Score (TSS) as measured by the Myelofibrosis-Symptom Assessment Form (MFSAF) v4.0, 7 day recall version, in patients with myelofibrosis administered PXS-5505. The MFSAF v4.0 assesses 7 core symptoms of myelofibrosis: fatigue, night sweats, pruritus, abdominal discomfort, pain under the left ribs, early satiety, and bone pain. Each symptom is rated on an 11-point scale from 0 (absent) to 10 (worst imaginable). The Total Symptom Score is calculated by adding the scores from each of the 7 individual symptoms. Therefore the range of possible scores is from 0 to 70, with a higher score indicating worse symptoms.

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

  11. Changes in Myelofibrosis Related Symptoms, Absolute Change in TSS

    Absolute changes from baseline in Total Symptom Score (TSS) as measured by the Myelofibrosis-Symptom Assessment Form (MFSAF) v4.0, 7 day recall version, in patients with myelofibrosis administered PXS-5505. The MFSAF v4.0 assesses 7 core symptoms of myelofibrosis: fatigue, night sweats, pruritus, abdominal discomfort, pain under the left ribs, early satiety, and bone pain. Each symptom is rated on an 11-point scale from 0 (absent) to 10 (worst imaginable). The Total Symptom Score is calculated by adding the scores from each of the 7 individual symptoms. Therefore the range of possible scores is from 0 to 70, with a higher score indicating worse symptoms. A positive absolute change is indicative of worsened symptoms compared to baseline. A negative absolute change is indicative of improved symptoms compared to baseline.

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

  12. Hematological Changes - % of Patients With Anemia Response, Minor Anemia Response, 50% Reduction in Transfusion Burden

    Patients with hemoglobin <100g/L at baseline who achieve an anemia response based on IWG-MRT criteria and who achieve a minor anemia response consistent with 2024 IWG-ELN criteria. Also, patients receiving transfusions at baseline who have a reduction of >=50% in transfusion units in any rolling 12 week period from week 12 onwards, compared to the 12 weeks prior to treatment. Derived from data on hemoglobin level and transfusions.

    Measured: Any time from week 12 to week 24 (expansion phase) or to week 52 (add-on phase)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Dec 2020
  2. Study start18 Feb 2021
  3. Primary completion9 Jul 2025
  4. Study completion9 Jul 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
43 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04676529
Sponsor's protocol ID
PXS5505-MF-101
Status last verified
Jul 2026
First submitted
8 Dec 2020
Last updated
4 Aug 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 40241543

  • Vachhani P, Baskar J, Charlton B, et al. PXS-5505-MF-101: a phase 1/2a study to evaluate safety, pharmacokinetics and pharmacodynamics of PXS-5505 in patients with primary, post-polycythemia vera or post-essential thrombocythemia myelofibrosis. Blood. 2023; 142 (Supplement 1): 625-7. https://doi.org/10.1182/blood-2023-181383

  • Tan P, Baker R, Lee SE, et al. Multicenter, Open-Label Phase 1/2a Study of PXS-5505 and Ruxolitinib in Patients with Primary, Post-Polycythemia Vera (PV) or Post-Essential Thrombocythemia (ET) Myelofibrosis. Blood. 2024; 144 (Supplement 1): 1001-2. https://doi.org/10.1182/blood-2024-204290

  • Baker R, Chen CC, Tsai YC, et al. A phase 1/2a trial of amsulostat, a novel pan-lysyl oxidase inhibitor, in patients with advanced myelobrosis as an add-on to ruxolitinib treatment for up to 52 weeks. Blood. 2025; 146 (Supplement): 2027-8. https://doi.org/10.1182/blood-2025-2027

  • Baker R, Baskar J, Charlton B, et al. Phase 1/2a 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. Blood. 2022; 140 (Supplement 1): 3947-8. https://doi.org/10.1182/blood-2022-158344

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing PXS-5505 in people with Myelofibrosis and Primary Myelofibrosis (PMF), run by Syntara at 23 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in South Korea, Australia, Taiwan, United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Subjects With Serious and Non-serious Adverse Events (time frame: Day 0 to follow-up visit (28 -1/+7days post-Tx end) after up to 4wks Tx [escalation phase]; Day 0 to follow-up visit (28±3days post-Tx end) after up to 24wks Tx [expansion]); Day 0 to follow-up visit (28± 3days post-Tx end) after up to 52wks Tx [add-on].). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04676529, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2026.

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