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

Completed · Phase 1/Phase 2

Conditions studied: Myelofibrosis, Primary Myelofibrosis (PMF), Post- Essential Thrombocythemia Myelofibrosis, Post Polycythemia Vera Myelofibrosis

In brief

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.

Key facts

Study ID: NCT04676529
Run by: Syntara
People needed: 43
Starts: 2021-02-18
Expected to finish: 2025-07-09
Last updated by the study team: 2026-08-04

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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);
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

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.

Where it is running

Comprehensive Cancer Center (UAB CCC) — Birmingham, Alabama, United States
Novant Health Cancer Institute — Winston-Salem, North Carolina, United States
The University of Texas MD Anderson Cancer Center — Houston, Texas, United States
Liverpool Hospital — Liverpool, New South Wales, Australia
Ashford Cancer Centre Research — Adelaide, South Australia, Australia
St Vincent's Hospital Melbourne — Fitzroy, Victoria, Australia
One Clinical Research — Perth, Western Australia, Australia
The Perth Blood Institute — West Perth, Western Australia, Australia
Inje University Busan Paik Hospital - Internal Medicine — Busan, Busan Gwang'yeogsi [Pusan-Kwan, South Korea
Keimyung University Dongsan Hospital — Daegu, Daegu Gwang'yeogsi [Taegu-Kwangyokshi], South Korea
Gachon University Gil Hospital — Incheon, Incheon Gwang'yeogsi [Inch'n-K, South Korea
National Cancer Center (Seoul Metro; northern) — Gyeonggi-do, South Korea
Seoul National University Hospital - Bundang — Gyeonggi-do, South Korea
Seoul National University Hospital — Seoul, South Korea
Severance Hospital, Yonsei University Health System- Haemat — Seoul, South Korea
Asan Medical Centre — Seoul, South Korea
Samsung Medical Center — Seoul, South Korea
The Catholic University of Korea, Seoul St. Mary's Hospital — Seoul, South Korea
Chang Gung Medical Foundation - ChiaYi Chang Gung Memorial Hospital - Hematology and Oncology — Chiayi City, Chiayi, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital — Kaohsiung City, Taiwan
China Medical University Hospital - Internal Medicine - Taichung — Taichung, Taiwan
National Cheng Kung University Hospital — Tainan, Taiwan
National Taiwan University Hospital - Hematology And Oncology — Taipei, Taiwan

Full record on ClinicalTrials.gov

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