Pacritinib for VEXAS Syndrome

Recruiting at 46 trial locations

Overseen By Study Physician

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Swedish Orphan Biovitrum

Must be taking: Glucocorticoids

Must not be taking: CYP3A4 inhibitors/inducers

Disqualifiers: Transplant, MDS, Malignancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

78 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether pacritinib is safe and effective for individuals with VEXAS syndrome, a rare condition affecting various body systems such as the skin, joints, and eyes. Participants will receive either one of two doses of pacritinib or a placebo (a harmless pill with no active drug) for comparison. Individuals with VEXAS syndrome symptoms affecting areas like the skin or lungs, who are on a stable dose of certain anti-inflammatory medications, might be suitable for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you must be on a stable dose of certain medications like prednisone or prednisolone. Some medications, like strong CYP3A4 inhibitors or inducers, must be stopped before joining the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that pacritinib has been studied for its safety in people with VEXAS syndrome. In some studies, about 53% of patients experienced serious side effects, with infections being common. Researchers have tested pacritinib at different doses to assess its effects on patients.

These studies aim to understand how well patients tolerate pacritinib. While the treatment remains under investigation, these studies provide important information about potential side effects. The current trial focuses on evaluating both the safety and effectiveness of the treatment, with researchers gathering more data to ensure patient safety. ^{1 2 3 4 5}

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

Pacritinib is unique for treating VEXAS Syndrome because it targets a specific enzyme called JAK2, which is involved in inflammation and immune response. Most current treatments for VEXAS Syndrome, such as corticosteroids or immunosuppressants, broadly suppress the immune system, which can lead to significant side effects. Pacritinib offers a more precise approach by focusing on the JAK2 pathway, potentially reducing inflammation with fewer side effects. Researchers are excited about this treatment because it could provide a more targeted and effective option for managing the symptoms of VEXAS Syndrome, improving patient outcomes.

What evidence suggests that pacritinib might be an effective treatment for VEXAS syndrome?

Research suggests that pacritinib could be a promising treatment for VEXAS syndrome, a rare condition that causes inflammation in the body. Pacritinib, a JAK inhibitor, reduces inflammation by blocking certain processes in the body. Studies have shown that pacritinib effectively treats myelofibrosis, a disease involving abnormal blood cells, indicating it might also help with VEXAS. Early results suggest that pacritinib can lessen symptoms and improve the quality of life for people with inflammatory conditions. However, more research is needed to confirm its effectiveness specifically for VEXAS syndrome. Participants in this trial will receive either pacritinib alone, pacritinib combined with a placebo, or a placebo alone to evaluate its effectiveness for VEXAS syndrome. ^{1 2 3 5 6}

Who Is on the Research Team?

Study Physician

Principal Investigator

Sobi, Inc.

Are You a Good Fit for This Trial?

This trial is for patients with VEXAS syndrome, a rare inflammatory condition. Participants must meet specific health criteria to join, but the provided information doesn't detail these requirements. Those eligible will be randomly assigned to different treatment groups.

Inclusion Criteria

My tests show a specific genetic mutation in my blood or bone marrow.

I am currently on a stable dose of steroids for my condition.

Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test within 30 days prior to enrollment and a negative urine pregnancy test on Day 1 prior to randomization and dosing

Exclusion Criteria

I have HIV that is not well-controlled, with or without medication.

I am not on steroids for conditions other than VEXAS syndrome that would affect the study.

I've been in ICU more than once for VEXAS Syndrome flare-ups in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-blind Treatment

Participants receive either pacritinib dose A, pacritinib dose B plus placebo, or placebo for up to 24 weeks

24 weeks

Open-label Treatment

Participants receive pacritinib in an open-label setting for up to 48 weeks

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pacritinib

Trial Overview The study tests pacritinib's effectiveness and safety in treating VEXAS syndrome. A total of 78 patients will receive either one of two doses of pacritinib or a placebo, with their group determined by chance and adjusted based on their current medication dosage.

How Is the Trial Designed?

Group I: Pacritinib + placebo Experimental Treatment 2 Interventions

To receive oral administration of pacritinib dose B plus placebo for up to 24 weeks

Group II: Pacritinib Experimental Treatment 1 Intervention

To receive oral administration of pacritinib dose A for up to 24 weeks.

Group III: Placebo Placebo Group 1 Intervention

To receive oral administration of placebo for up to 24 weeks.

Who Is Running the Clinical Trial?

Swedish Orphan Biovitrum

Lead Sponsor

Trials

103

Recruited

13,300+

Dr. Guido Oelkers

Swedish Orphan Biovitrum

Chief Executive Officer since 2017

PhD in Economics

Dr. Lydia Abad-Franch

Swedish Orphan Biovitrum

Chief Medical Officer since 2023

MD, MBA

PSI CRO

Industry Sponsor

Trials

13

Recruited

2,800+

Published Research Related to This Trial

Pacritinib, particularly at a dose of 200 mg twice per day, showed significant efficacy in treating advanced myelofibrosis in patients who were intolerant or resistant to ruxolitinib, with a spleen volume response rate of 9.3%.

The study demonstrated an acceptable safety profile for pacritinib, with no increase in severe hemorrhagic or cardiac events at the highest dose, making it a promising option for patients with severe thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determining the recommended dose of pacritinib: results from the PAC203 dose-finding trial in advanced myelofibrosis. Gerds, AT., Savona, MR., Scott, BL., et al.[2021]

Pacritinib was found to be well tolerated in patients with myelofibrosis, with a maximum tolerated dose established at 500 mg once daily and a recommended phase 2 dose of 400 mg once daily, showing manageable side effects and a low incidence of severe myelosuppression.

In the phase 2 part of the study, 23.5% of patients achieved a significant reduction in spleen volume after 24 weeks, indicating clinical activity, while 38.9% reported improved quality of life, highlighting its potential as an effective treatment for myelofibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1/2 study of pacritinib, a next generation JAK2/FLT3 inhibitor, in myelofibrosis or other myeloid malignancies. Verstovsek, S., Odenike, O., Singer, JW., et al.[2022]

Pacritinib has shown promising efficacy in treating myelofibrosis (MF), with 31% of patients experiencing a significant reduction in spleen volume and 42% showing improvement in spleen size through physical examination after 24 weeks.

The treatment demonstrated a favorable safety profile, particularly for patients with preexisting anemia and thrombocytopenia, although common side effects included diarrhea and nausea, leading to treatment discontinuation in 26% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a phase 2 study of pacritinib (SB1518), a JAK2/JAK2(V617F) inhibitor, in patients with myelofibrosis. Komrokji, RS., Seymour, JF., Roberts, AW., et al.[2022]

Pacritinib is a potent inhibitor of JAK2 and FLT3 that shows clinical efficacy in treating myelofibrosis without causing myelosuppression, which is a common side effect of other JAK inhibitors.

The drug selectively inhibits JAK2 while sparing JAK1, and it also reduces harmful cytokines, suggesting potential therapeutic benefits in other blood cancers and inflammatory diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive kinase profile of pacritinib, a nonmyelosuppressive Janus kinase 2 inhibitor. Singer, JW., Al-Fayoumi, S., Ma, H., et al.[2022]

Pacritinib is a selective inhibitor of Janus kinase 2 and FMS-related tyrosine kinase 3, showing potential for treating blood cancers like myeloproliferative neoplasias and acute myeloid leukemia, with strong antiproliferative effects and the ability to induce cell death.

In early-phase clinical trials, pacritinib demonstrated promising efficacy and an acceptable safety profile, with mild to moderate gastrointestinal issues being the most common side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profile of pacritinib and its potential in the treatment of hematologic disorders. Hatzimichael, E., Tsolas, E., Briasoulis, E.[2022]

In a study involving 536 myelofibrosis patients, pacritinib demonstrated superior efficacy in reducing spleen size and improving symptoms compared to best available therapy, particularly in patients with low or absent JAK2V617F allele burden.

Pacritinib was effective across all JAK2V617F allele burden quartiles, showing significant spleen response rates in patients with low allele burden (0%-25% and 25%-50%), while no responses were observed in the best available therapy group for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pacritinib demonstrates spleen volume reduction in patients with myelofibrosis independent of JAK2V617F allele burden. Tremblay, D., Mesa, R., Scott, B., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06538181

Pacritinib in Vacuoles, E1 Ubiqutin-activating Enzyme, X ... The investigators propose a single arm, pilot Phase 1 study evaluating the safety and tolerability of pacritinib in patients with VEXAS syndrome with an initial ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0003496725017984

POS0379 PAXIS: A RANDOMIZED, DOUBLE-BLIND ... It is designed to assess pacritinib in adult patients with VEXAS syndrome. Inclusion criteria include documented evidence of past inflammatory involvement and ...

3. mayo.edu mayo.edu/research/clinical-trials/cls-20584216

A study to assess the effectiveness and safety of pacritinib ... The purpose of this stduy is to evaluate the efficacy of two dose levels of pacritinib compared to placebo during the double-blind treatment period in patients ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12297003/

Promise of Jak Inhibition in the Management of VEXAS ... Jak inhibitor Pacritinib is used to treat myelofibrosis. Clinical trial is underway to study efficacy of Pacritinib in VEXAS (Clinical trial ...

5. sobi.com sobi.com/usa/en/news-releases/data-presented-acr-convergence-2025-highlight-sobis-commitment-advancing-care-across-rare-and-underserved-inflammatory-conditions

Data presented at ACR Convergence 2025 highlight Sobi's ... ... Efficacy and Safety of Pacritinib in Patients with VEXAS Syndrome. An oral presentation on the design of a randomized, double-blind, placebo ...

6. ctv.veeva.com ctv.veeva.com/study/a-study-to-assess-the-effectiveness-and-safety-of-pacritinib-in-patients-with-vexas-syndrome-paxis

A Study to Assess the Effectiveness and Safety of Pacritinib in ... This study is to assess the effectiveness and safety of pacritinib in patients with VEXAS (ie, Vacuoles in myeloid progenitors, E1 ubiquitin-activating enzyme, ...