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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04676529




Registration number
NCT04676529
Ethics application status
Date submitted
8/12/2020
Date registered
21/12/2020

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
PXS5505-MF-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelofibrosis 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PXS-5505

Experimental: PXS-5505, Dose Level 1, Escalation Phase (Cohort A) - Patients will receive PXS-5505 dose level 1, twice daily for a period of 4 weeks.

Experimental: PXS-5505, Dose Level 2, Escalation Phase (Cohort B) - Patients will receive PXS-5505 dose level 2, twice daily for a period of 4 weeks.

Experimental: PXS-5505, Dose Level 3, Escalation Phase (Cohort C) - Patients will receive PXS-5505 dose level 3, twice daily for a period of 4 weeks.

Experimental: PXS-5505, Expansion Phase - 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.

Experimental: PXS-5505, Add-on Phase - 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.


Treatment: Drugs: PXS-5505
PXS-5505 is a hard capsule (size 0) with the additional excipients mannitol and magnesium stearate.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of subjects with serious and non-serious adverse events
Timepoint [1] 0 0
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 outcome [1] 0 0
Maximum plasma concentration (C1hr=Cmax)
Timepoint [1] 0 0
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
Secondary outcome [2] 0 0
Minimum plasma concentration (Cmin)
Timepoint [2] 0 0
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
Secondary outcome [3] 0 0
Lysyl oxidase and lysyl oxidase-like 2 inhibition in plasma
Timepoint [3] 0 0
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
Secondary outcome [4] 0 0
Change in bone marrow (BM) fibrosis
Timepoint [4] 0 0
Day 0, Week 12 and Week 24 (cohort expansion and add-on phase), and week 52 during add-on phase only
Secondary outcome [5] 0 0
Response rate
Timepoint [5] 0 0
At week 12 and week 24 (cohort expansion and add-on phase), weeks 38 and 52 during add-on phase only
Secondary outcome [6] 0 0
Changes in spleen volume
Timepoint [6] 0 0
Day 0, week 12, and week 24 (cohort expansion and add-on phase), weeks 38 and 52 during add-on phase only
Secondary outcome [7] 0 0
Changes in myelofibrosis related symptoms
Timepoint [7] 0 0
Screening, week 12, and week 24 (cohort expansion and add-on phase), weeks 38 and 52 during add-on phase only
Secondary outcome [8] 0 0
Percentage of patients with hematological changes
Timepoint [8] 0 0
Day 0, week 12, and 24 (cohort expansion and add-on phase), weeks 38 and 52 during add-on phase only

Eligibility
Key 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
* 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
* 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/02/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/08/2025
Actual
Sample size
Target
Accrual to date
Final
43
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 0 0
Ashford Cancer Centre Research - Adelaide
Recruitment hospital [3] 0 0
St Vincent's Hospital Melbourne - Fitzroy
Recruitment hospital [4] 0 0
One Clinical Research - Perth
Recruitment hospital [5] 0 0
The Perth Blood Institute - West Perth
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
5037 - Adelaide
Recruitment postcode(s) [3] 0 0
3065 - Fitzroy
Recruitment postcode(s) [4] 0 0
6009 - Perth
Recruitment postcode(s) [5] 0 0
6005 - West Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
North Carolina
Country [3] 0 0
United States of America
State/province [3] 0 0
Texas
Country [4] 0 0
Korea, Republic of
State/province [4] 0 0
Busan Gwang'yeogsi [Pusan-Kwan
Country [5] 0 0
Korea, Republic of
State/province [5] 0 0
Daegu Gwang'yeogsi [Taegu-Kwangyokshi]
Country [6] 0 0
Korea, Republic of
State/province [6] 0 0
Incheon Gwang'yeogsi [Inch'n-K
Country [7] 0 0
Korea, Republic of
State/province [7] 0 0
Gyeonggi-do
Country [8] 0 0
Korea, Republic of
State/province [8] 0 0
Seoul
Country [9] 0 0
Taiwan
State/province [9] 0 0
Chiayi
Country [10] 0 0
Taiwan
State/province [10] 0 0
Kaohsiung
Country [11] 0 0
Taiwan
State/province [11] 0 0
Taichung
Country [12] 0 0
Taiwan
State/province [12] 0 0
Tainan
Country [13] 0 0
Taiwan
State/province [13] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Syntara
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jana Baskar, MBBS MMedSc MBA
Address 0 0
Syntara
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Jana Baskar, MBBS MMedSc MBA
Address 0 0
Country 0 0
Phone 0 0
+61 487 651 726
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04676529