Pacritinib for VEXAS Syndrome

Recruiting at 1 trial location

Overseen By Meagan A Jacoby, M.D., Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Washington University School of Medicine

Must not be taking: Immunosuppressants, DMARDs, Biologics, others

Disqualifiers: Recent thrombotic events, Active infection, Cardiovascular disease, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests pacritinib, a new treatment, to determine its effectiveness for VEXAS syndrome, a rare disorder causing inflammation and blood problems without a standard treatment. The trial aims to assess the safety of pacritinib and its ability to address VEXAS syndrome symptoms. It seeks participants with a confirmed UBA1 mutation and symptoms such as frequent skin rashes, joint pain, or inflammation. As a Phase 1 trial, this research focuses on understanding how pacritinib works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires a 28-day washout period (time without taking certain medications) for those currently on another JAK inhibitor or investigational agents. If you're on immunosuppressants, DMARDs, biologic cytokine inhibitors, or strong CYP3A4 inhibitors/inducers, you may also need a 28-day washout. A stable corticosteroid dose must be maintained for at least 14 days before starting pacritinib.

Is there any evidence suggesting that pacritinib is likely to be safe for humans?

Research has shown that pacritinib has been studied in patients with myelofibrosis, a blood condition, and has a manageable safety profile. The most common side effects in these studies included diarrhea, low platelet counts (thrombocytopenia), nausea, low red blood cell count (anemia), and swelling in the limbs (peripheral edema). These side effects occurred in about 20% or more of patients treated with pacritinib.

The FDA currently approves pacritinib for treating myelofibrosis, indicating it has been found somewhat safe for that condition. However, the current trial for VEXAS syndrome is in an early stage. The main goal is to determine if the treatment is safe for this specific condition. If pacritinib is well-tolerated by a small group of VEXAS patients, the study will continue to further evaluate its safety and effectiveness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pacritinib is unique for treating VEXAS Syndrome because it specifically targets JAK2, a key player in inflammatory processes. Most treatments for VEXAS Syndrome focus on general immunosuppression or symptom management, like corticosteroids or immunosuppressants, which can have broad and sometimes harsh effects on the body. Pacritinib's targeted approach potentially means fewer side effects and more effective management of the syndrome's symptoms. Researchers are excited because it offers a more precise way to address the underlying inflammation driving the condition.

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

Research has shown that pacritinib may help treat conditions like VEXAS syndrome by blocking certain enzymes involved in inflammation and blood cell production. In this trial, participants will receive pacritinib in one of two treatment arms: a Dose De-Escalation (Safety Run-in) arm or a Dose Expansion arm. Other studies have demonstrated that pacritinib reduces symptoms in patients with similar blood disorders, such as myelofibrosis. This suggests it might also help manage the inflammation and blood-related symptoms of VEXAS syndrome. Although data specifically on VEXAS is limited, the drug's success in similar conditions offers hope for its effectiveness here. ^{1 5 6 7 8}

Who Is on the Research Team?

Meagan Jacoby, M.D., Ph.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for patients with VEXAS syndrome, a severe autoinflammatory disorder without standard treatment options. Participants must have specific genetic changes in the UBA1 gene and suffer from related hematologic and rheumatologic issues.

Inclusion Criteria

I can understand and am willing to sign the consent form.

I have VEXAS syndrome and haven't used JAK inhibitors. I've been on a stable dose of corticosteroids for 2 weeks.

I've used a JAK inhibitor other than pacritinib, but it didn't control my symptoms or let me reduce steroids.

Exclusion Criteria

I have previously taken pacritinib.

Currently receiving any other investigational agents. Patients may be eligible after 28 day washout.

A history of allergic reactions attributed to compounds of similar chemical or biologic composition to pacritinib.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-in

Initial safety run-in phase with 6 patients treated with pacritinib 200mg BID on days 1-28 of a continuous 28-day cycle

4 weeks

1 visit (in-person) per cycle

Expansion

Expansion cohort to gain additional toxicity and efficacy data, with treatment up to 12 cycles

12 months

1 visit (in-person) per cycle

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, a drug thought to help with VEXAS syndrome symptoms due to its action on certain enzymes. It's a Phase 1 trial starting with six people taking the drug daily for four weeks to check safety before possibly expanding to fifteen patients.

How Is the Trial Designed?

Group I: Dose Expansion: Pacritinib Experimental Treatment 0 Interventions

Recommended phase II dose of pacritinib by mouth twice per day. Each cycle is 28 days and participants can receive up to 12 cycles of treatment.

Group II: Dose De-Escalation (Safety Run-in): Pacritinib Experimental Treatment 0 Interventions

Assigned dose of pacritinib by mouth twice per day. Each cycle is 28 days and participants can receive up to 12 cycles of treatment.

Pacritinib is already approved in United States for the following indications:

Approved in United States as Vonjo for:

• Intermediate or high-risk primary or secondary myelofibrosis with platelet counts below 50 × 10^9/L

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Swedish Orphan Biovitrum

Industry 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

Citations

1. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-01860

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

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03165734

NCT03165734 | A Phase 3 Study of Pacritinib in Patients ... The study is a randomized, controlled phase 3 study comparing the efficacy of pacritinib with P/C therapy in patients with PMF, PPV-MF, or PET-MF.

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. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-effectiveness-and-safety-of-pacritinib-for-patients-with-vexas-syndrome/

Study of pacritinib effectiveness and safety compared to ... This clinical trial evaluates the effectiveness and safety of Pacritinib in treating symptoms of the rare condition known as VEXAS syndrome.

5. dana-farber.org dana-farber.org/clinical-trials/25-202

PAXIS: A randomized, double-blind, placebo-controlled ... This study is to assess the effectiveness and safety of pacritinib in patients with VEXAS (ie, Vacuoles in myeloid progenitors, E1 ubiquitin-activating enzyme, ...

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-00931

Pacritinib for the Treatment of Patients with VEXAS Syndrome This phase I trial tests the safety, side effects, best dose and effectiveness of pacritinib for treating patients with vacuoles, E1 ubiqutin-activating enzyme.

7. vonjohcp.com vonjohcp.com/

VONJO® (pacritinib) HCP: VONJO® for Myelofibrosis Treatment In PERSIST-2, the most common adverse reactions in ≥20% of patients (n=106) were diarrhea, thrombocytopenia, nausea, anemia, and peripheral edema. Learn more ...

8. trialx.com trialx.com/clinical-trials/listings/294716/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 ... This study is to assess the effectiveness and safety of pacritinib in patients with VEXAS (i.e., Vacuoles in myeloid progenitors, E1 ubiquitin- ...