PXS-5505 for Myelofibrosis

Recruiting at 26 trial 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

Trial Summary

What is the purpose of this trial?

This trial tests a new drug, PXS-5505, for safety and tolerance in patients with specific bone marrow disorders. It aims to find the best dose and see if combining it with another medication improves treatment.

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.

How does the drug PXS-5505 differ from other treatments for myelofibrosis?

PXS-5505 is unique because it targets lysyl oxidase (LOX), an enzyme involved in collagen cross-linking and tissue stiffening, which is upregulated in myelofibrosis. This approach is different from the commonly used JAK inhibitors like ruxolitinib, as it directly addresses the fibrotic component of the disease. ^{1 2 3 4 5}

Research Team

Jana Baskar, MBBS MMedSc MBA

Principal Investigator

Syntara

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

References

1. Italy 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. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Trends in overall mortality among US veterans with primary myelofibrosis. [2023]

3. Japan pubmed.ncbi.nlm.nih.gov

Novel lysyl oxidase inhibitors attenuate hallmarks of primary myelofibrosis in mice. [2020]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Rationale for combination therapy in myelofibrosis. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

A phase 2 study of ruxolitinib in combination with azacitidine in patients with myelofibrosis. [2021]