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

  • STATUS
    Recruiting
  • End date
    Jul 14, 2023
  • participants needed
    24
  • sponsor
    Pharmaxis
Updated on 21 October 2022

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.

Description

The study consists of two phases: a dose escalation phase and a cohort expansion 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.

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

Details
Condition Myelofibrosis
Treatment PXS-5505
Clinical Study IdentifierNCT04676529
SponsorPharmaxis
Last Modified on21 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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
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
Have intermediate -2, or high-risk disease according to the International Working
Have symptomatic disease according to the MFSAF v4.0
Group prognostic scoring system (DIPSS)
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
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
Eastern Cooperative Oncology Group performance status ≤ 2
Cohort Expansion 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 5 months of the re-initiation of treatment with PXS-5505 if subject participated in dose escalation phase of the trial

Exclusion Criteria

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
Symptomatic congestive heart failure (New York Heart Association Classification Class II), unstable angina, or unstable cardiac arrhythmia requiring medication
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
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
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Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

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