PXS-5505 for Myelofibrosis

Recruiting in Cleveland (>99 mi)

+38 other locations

Overseen By Jana Baskar, MBBS MMedSc MBA

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Syntara

Must be taking: Ruxolitinib

Must not be taking: Cytotoxic agents

Disqualifiers: HIV, Active hepatitis, Recent cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

43 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called PXS-5505 for myelofibrosis, a condition where scar tissue builds up in the bone marrow. The study aims to determine the safety and effectiveness of PXS-5505, both alone and in combination with another drug, ruxolitinib. People with myelofibrosis who are either on a stable dose of ruxolitinib or not eligible for certain other treatments might be suitable for this trial. Participants will receive PXS-5505 in various ways, depending on their current treatment plan, to assess any side effects and benefits. As a Phase 1/Phase 2 trial, this research seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants the chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial requires that participants not be on ruxolitinib or fedratinib unless they are part of the add-on phase, where they must have been on a stable dose of ruxolitinib for at least 8 weeks. Other medications like cytotoxic agents, corticosteroids above a certain dose, and immune modulators must be stopped at least two weeks before starting the study.

Is there any evidence suggesting that PXS-5505 is likely to be safe for humans?

Research has shown that PXS-5505 is generally safe for people with myelofibrosis. In studies, even the highest dose tested—200 mg taken twice a day—was well-tolerated by patients. This dose also effectively reduced the activity of lysyl oxidase, an enzyme linked to tissue thickening or scarring.

Reports so far suggest that PXS-5505 is not only safe but might also help relieve symptoms for those with myelofibrosis. It is important to note that these findings come from early testing stages, which primarily focus on ensuring the treatment's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for myelofibrosis?

Researchers are excited about PXS-5505 for treating myelofibrosis because it offers a fresh approach compared to current options. Most treatments for myelofibrosis, like ruxolitinib, focus on managing symptoms and reducing spleen size by inhibiting JAK pathways. PXS-5505, however, targets the lysyl oxidase (LOX) enzyme, which is involved in the fibrotic process. This novel mechanism could potentially modify the disease itself, rather than just addressing symptoms, offering hope for more effective long-term management of myelofibrosis.

What evidence suggests that PXS-5505 might be an effective treatment for myelofibrosis?

Research has shown that PXS-5505 holds promise for treating myelofibrosis. Early studies indicate that it is safe for patients and quickly reaches stable levels in the body. Initial signs suggest it may help reduce symptoms and improve collagen fibrosis, which involves the thickening and scarring of connective tissue. PXS-5505 blocks an enzyme called lysyl oxidase, which plays a role in forming and maintaining fibrous tissue, potentially altering disease progression. In this trial, participants may receive PXS-5505 alone or with a JAK inhibitor, which might further aid in reversing bone marrow fibrosis. Although research is ongoing, these early results offer hope for those seeking new treatment options. ^{3 4 6 7 8}

Who Is on the Research Team?

Jana Baskar, MBBS MMedSc MBA

Principal Investigator

Syntara

Are You a Good Fit for This Trial?

This trial is for patients with primary myelofibrosis or those who developed it after essential thrombocythemia/polycythemia vera. They should not be candidates for stem cell transplantation and must have stopped certain treatments like ruxolitinib or fedratinib. Participants need to have a specific risk level of disease, show symptoms, and have good organ function. Men and women must agree to use contraception.

Inclusion Criteria

I am not eligible for a stem cell transplant.

My condition is classified as intermediate-2 or high-risk by DIPSS.

You are expected to live for at least six more months.

Exclusion Criteria

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

I haven't had surgery in the last two weeks and don't plan to during or right after the study.

I have had an aneurysm in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive PXS-5505 at escalating doses to determine safety and optimal dosing

4 weeks

Weekly visits for dose adjustments and monitoring

Cohort Expansion

Participants receive PXS-5505 at the determined optimal dose to further assess safety and efficacy

24 weeks

Visits at weeks 0, 4, 12, and 24

Add-on Phase

Participants receive PXS-5505 in addition to a stable dose of ruxolitinib to assess long-term safety and efficacy

52 weeks

Visits at weeks 0, 4, 12, 24, 38, and 52

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit post-treatment

What Are the Treatments Tested in This Trial?

Interventions

• PXS-5505

Trial Overview The study tests PXS-5505's safety and how the body responds to different doses in people with myelofibrosis that started on its own or after other blood conditions. It's an early-stage trial (phase 1/2a) where everyone gets the drug openly without any placebo control.

How Is the Trial Designed?

Group I: PXS-5505, Expansion Phase Experimental Treatment 1 Intervention

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.

Group II: PXS-5505, Dose Level 3, Escalation Phase (Cohort C) Experimental Treatment 1 Intervention

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

Group III: PXS-5505, Dose Level 2, Escalation Phase (Cohort B) Experimental Treatment 1 Intervention

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

Group IV: PXS-5505, Dose Level 1, Escalation Phase (Cohort A) Experimental Treatment 1 Intervention

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

Group V: PXS-5505, Add-on Phase Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Syntara

Lead Sponsor

Trials

35

Recruited

3,100+

Pharmaxis

Lead Sponsor

Trials

35

Recruited

3,100+

Parexel

Industry Sponsor

Trials

322

Recruited

137,000+

Peyton Howell

Parexel

Chief Executive Officer

Master of Healthcare Administration from The Ohio State University, Bachelor of Arts in Health Communications from the University of Illinois

Dr. Austin Smith

Parexel

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Published Research Related to This Trial

The combination of ruxolitinib and nilotinib showed a synergistic effect against myelofibrosis (MF) cells, with a significant reduction in drug concentration needed to achieve efficacy, indicating a promising new treatment strategy.

Adding prednisone to the ruxolitinib/nilotinib combination further enhanced its effectiveness by inhibiting key signaling pathways involved in MF, suggesting a multi-faceted approach to therapy that targets both proliferation and fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib in combination with prednisone and nilotinib exhibit synergistic effects in human cells lines and primary cells from myeloproliferative neoplasms. Cortés, AA., Diaz, RA., Hernández-Campo, P., et al.[2022]

In a phase 2 study of 46 patients with myelofibrosis, the combination of ruxolitinib and azacitidine led to a 72% response rate, with significant improvements in spleen size and bone marrow fibrosis over a median follow-up of 28 months.

The treatment was generally safe, with only 9% of patients discontinuing due to drug-related toxicities, although some experienced severe anemia and thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2 study of ruxolitinib in combination with azacitidine in patients with myelofibrosis. Masarova, L., Verstovsek, S., Hidalgo-Lopez, JE., et al.[2021]

Citations

1. haematologica.org haematologica.org/article/view/12032

A phase I/IIa trial of PXS-5505, a novel pan-lysyl oxidase ... PXS-5505 was well tolerated and reached steady-state concentrations by day 28. Over the 24-week treatment period preliminary indications of ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40241543/

A phase I/IIa trial of PXS-5505, a novel pan-lysyl oxidase ... PXS-5505 was well tolerated and reached steady-state concentrations by day 28. Over the 24-week treatment period preliminary indications of clinical efficacy, ...

3. mpn-hub.com mpn-hub.com/medical-information/pxs-5505-in-advanced-mf-results-of-a-phase-iiia-trial

PXS-5505 in advanced MF: Results of a phase I/IIa trial In the CEP, 92% of treatment-emergent adverse events were not related to PXS-5505 treatment and most were mild. PXS-5505 reached steady-state ...

4. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/1001/530414/Multicenter-Open-Label-Phase-1-2a-Study-of-Pxs

Multicenter, Open-Label Phase 1/2a Study of Pxs-5505 and ... Thus, a pan-LOX inhibitor such as PXS-5505 combined with a JAK inhibitor may help to modify the MF disease trajectory by reversing BM fibrosis, ...

5. bloodcancerstoday.com bloodcancerstoday.com/post/pxs-5505-may-close-the-treatment-gap-in-advanced-myelofibrosis

PXS-5505 May Close the Treatment Gap in Advanced ... Their findings suggest that treatment with novel LOX inhibitor PXS-5505 led to symptom relief and collagen fibrosis improvement in patients with ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04676529

NCT04676529 | Study to Evaluate Safety, Pharmacokinetic ... 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 ...

7. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/625/502732/PXS5505-MF-101-A-Phase-1-2a-Study-to-Evaluate

PXS5505-MF-101: A Phase 1/2a Study to Evaluate Safety ... PXS-5505 is a pan-LOX inhibitor that prevents the cross-linking of collagen and elastin and exhibits anti-fibrotic effects in murine models of MF.

8. bloodcancerstoday.com bloodcancerstoday.com/post/promising-tolerability-and-symptom-reduction-using-pxs-5505-in-myelofibrosis

Promising Tolerability and Symptom Reduction Using PXS ... Thus far, results of this study support the exploration of PXS-5505 due to its safety and potential therapeutic benefit for participants with MF ...