What side effects are associated with this type of intervention?

Common treatments for Myelofibrosis include JAK inhibitors like ruxolitinib and fedratinib, which can cause anemia, thrombocytopenia, gastrointestinal symptoms, and elevated liver enzymes. Fedratinib specifically has been associated with encephalopathy, cardiovascular events, and liver toxicity. Lysyl oxidase inhibitors, such as those targeting LOXL2/LOXL3, are being studied for their antifibrotic effects by inhibiting collagen cross-linking. While specific side effects for PXS-5505 are not detailed, potential side effects may include those related to extracellular matrix modulation, such as tissue remodeling complications.

What prior FDA approvals exist?

The FDA has approved several treatments for Myelofibrosis, primarily focusing on JAK inhibitors such as ruxolitinib and fedratinib. These drugs work by inhibiting the JAK-STAT pathway, which is involved in the pathogenesis of Myelofibrosis. While these treatments help manage symptoms and reduce spleen size, they do not directly target fibrosis. PXS-5505, a lysyl oxidase inhibitor, represents a novel approach by targeting the cross-linking of collagen and elastin fibers in the extracellular matrix, potentially addressing the fibrotic component of the disease more directly.

What other types of research exist?

Promising novel alternatives to PXS-5505 for Myelofibrosis patients include: 1) JAK2/1 inhibitors like ruxolitinib, which have shown combined anti-fibrotic and anti-inflammatory properties. 2) EW-7197, a TGF-β/Smad signaling inhibitor, which has demonstrated efficacy in reducing fibrosis in multiple organ systems. 3) Pentraxin 2, which inhibits monocyte differentiation into profibrotic fibrocytes and reduces TGF-beta1 production, showing potential in slowing fibrosis progression.

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Histone Deacetylase Inhibitor

PXS-5505 for Myelofibrosis

Phase 1 & 2

Waitlist Available

Research Sponsored by Syntara

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients who are not eligible for stem cell transplantation

Have intermediate -2, or high-risk disease according to the International Working Group prognostic scoring system (DIPSS)

Must not have

History of aneurysm

Prior splenectomy, or planning to undergo splenectomy, or splenic irradiation within 3 months prior to the first dose of study treatment

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 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]

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

While specific side effects are not listed here, phase 1/2a trials like this one generally monitor for any adverse reactions ranging from mild issues such as nausea or headaches to more serious ones including organ-related complications.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am not eligible for a stem cell transplant.

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

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My diagnosis is primary myelofibrosis or post-ET/PV myelofibrosis with at least Grade 2 marrow fibrosis.

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I can take care of myself and am up and about more than half of my waking hours.

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I agree to use approved birth control methods during and 90 days after the study.

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I've needed frequent blood transfusions or had severe side effects from ruxolitinib or fedratinib.

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I have symptoms as per the MFSAF v4.0 scale.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had an aneurysm in the past.

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I have had, or will have, my spleen removed or treated with radiation recently.

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I have heart issues like heart failure, chest pain, or irregular heartbeat that need medication.

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I have a history of HIV, active hepatitis B, or C.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 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]

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~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]

This trial's timeline: 3 weeks for screening, Varies for treatment, and 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] for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number of subjects with serious and non-serious adverse events

Secondary study objectives

Change in bone marrow (BM) fibrosis

Changes in myelofibrosis related symptoms

Changes in spleen volume

+5 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

5Treatment groups

Experimental Treatment

Group I: PXS-5505, Expansion PhaseExperimental Treatment1 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 Treatment1 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 Treatment1 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 Treatment1 Intervention

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

Group V: PXS-5505, Add-on PhaseExperimental Treatment1 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.

0 / 11Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Myelofibrosis include JAK inhibitors, such as ruxolitinib, which reduce inflammation and fibrosis by inhibiting the JAK-STAT pathway, and lysyl oxidase inhibitors like PXS-5505, which target fibrosis by preventing the cross-linking of collagen and elastin fibers in the extracellular matrix. These treatments are crucial for Myelofibrosis patients as they help manage symptoms, reduce spleen size, and potentially slow disease progression by addressing the underlying fibrotic processes that characterize the disease.

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