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Assessing the effectiveness of pacritinib for VEXAS syndrome

PAXIS: A Randomized, Double-blind, Placebo-controlled Dose-finding Phase 2 Study (Part 1) Followed by an Open-label Period (Part 2) to Assess the Efficacy and Safety of Pacritinib in Patients With VEXAS Syndrome

Phase 2 Interventional Swedish Orphan Biovitrum · NCT06782373

This study is testing if the drug pacritinib can help people with VEXAS syndrome manage their symptoms better while reducing their need for steroids.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment78 (estimated)
Ages18 Years and up
SexAll
SponsorSwedish Orphan Biovitrum Industry-sponsored
Drugs / interventionspacritinib, prednisone
Locations39 sites (Scottsdale, Arizona and 38 other locations)
Trial IDNCT06782373 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and effectiveness of pacritinib in patients with VEXAS syndrome, a rare autoinflammatory condition. It is a randomized, multicenter, double-blind, placebo-controlled phase 2 study involving 78 patients who will be assigned to receive either pacritinib or a placebo over a 24-week period. Patients must be receiving glucocorticoid therapy and will be monitored for flare prevention after tapering their glucocorticoids. Following the initial treatment phase, participants may continue with open-label pacritinib treatment for an additional 48 weeks.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with documented pathogenic mutations associated with VEXAS syndrome and currently receiving glucocorticoid therapy.

Not a fit: Patients who do not have a confirmed pathogenic mutation in UBA1 or are not currently on glucocorticoid therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the frequency of VEXAS flares and improve the quality of life for affected patients.

How similar studies have performed: While this approach is novel for VEXAS syndrome, similar studies targeting autoinflammatory conditions have shown promising results.

Eligibility criteria

Show full inclusion / exclusion criteria 
Key Inclusion Criteria:

* Documented evidence of a pathogenic mutation at methionine-41 (M41) or neighboring splice site mutation (c.118-1, c.118-2) position in UBA1 mutation based on myeloid next-generation sequencing (NGS) droplet digital polymerase chain reaction (ddPCR), or Sanger sequencing in peripheral blood or bone marrow samples.
* Current or documented evidence of past inflammatory involvement within 6 months prior to enrollment of at least one of the following organ systems by VEXAS syndrome: cutaneous (e.g., neutrophilic dermatosis, cutaneous vasculitis), vasculature (e.g., vasculitis), musculoskeletal (e.g., chondritis, arthritis), ocular (e.g., uveitis, scleritis), periorbital (e.g. periorbital edema), genitourinary (e.g., epididymitis), or pulmonary (e.g., alveolitis).
* Receiving ongoing GC therapy (stable prednisone or prednisolone dose of 15-45 mg/day) leading up to enrollment.
* Karnofsky Performance Status ≥50%
* Adequate organ function, meeting all the following criteria within 30 days prior to enrollment:

  1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × upper limit of normal (ULN)
  2. Total bilirubin ≤4 × ULN (≤8 × ULN in the setting of Gilbert's syndrome)
  3. Creatinine clearance (CrCl) ≥30 mL/min based on the Cockcroft-Gault formula
  4. Absolute neutrophil count ≥500/μL
  5. Prothrombin time (PT) or international normalized ratio (INR) ≤1.5 × ULN (unless prolonged due to therapeutic anticoagulation)
  6. Partial thromboplastic time (PTT) or activated PTT ≤1.5 × ULN (unless prolonged due to therapeutic anticoagulation)
  7. Platelet count ≥25 × 10\^9/L (value must be obtained in the absence of platelet transfusion in the prior 7 days)
  8. Peripheral blasts \<5%
* QT corrected by the Fridericia method (QTcF) ≤450 msec in males or ≤470 msec in females. Participants with QRS prolongation \>100 msec may enroll if their QTcF is ≤480 msec. If QTcF is thought to be prolonged due to a modifiable factor (e.g., medication / electrolyte abnormality), QTcF may be reevaluated.
* 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.
* WOCBP and male participants must agree to use a highly effective method of contraception starting at the first dose of trial therapy through 30 days after the last dose of trial therapy.

Key Exclusion Criteria

* Prior allogenic hematopoietic stem cell transplant (allo-HSCT) or solid organ transplant (other than corneal).
* Current use of systemic GCs for conditions other than VEXAS syndrome, which, in the opinion of the Investigator, would interfere with adherence to a GC taper regimen and/or assessment of efficacy.
* More than one prior admission to an intensive care unit due to a VEXAS Syndrome flare within the prior 6 months.
* Received ≥9 units of intensive red blood cell (RBC) transfusions in the 90 days prior to enrollment.
* Known concurrent myelodysplastic syndrome (MDS) requiring antineoplastic treatment, or allo-HSCT, or known high-risk or very high-risk MDS based on the Revised International Prognostic Scoring System (IPSS-R). Participants with MDS who do not meet these criteria may enroll.
* Malignancy within 1 year prior to enrollment with the exception of MDS (per exclusion criterion), curatively treated non-melanoma skin cancer, or curatively treated carcinoma in situ. Participants with pre-malignant hematologic conditions (e.g., monoclonal gammopathy of unknown significance \[MGUS\], clonal cytopenia of unknown significance) may enroll.
* Exposure to hypomethylating agents (HMA) within 6 months prior to enrollment, or exposure to more than 6 cycles of HMAs at any time.
* Exposure to non-GC anti-inflammatory therapy or hematologic support therapy within protocol defined timeframes prior to enrollment
* Exposure to anti-platelet therapy with the exception of low-dose aspirin (≤100 mg daily) within 28 days prior to enrollment.
* Known concomitant multiple myeloma, or serum M-protein ≥3 g/dL, involved-to uninvolved free light chain (FLC) ratio ≥100, or involved FLC level ≥100 mg/dL. Participants with MGUS may enroll.
* Systemic treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor or inducer within 5 half-lives prior to enrollment.
* Significant recent bleeding history defined as National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) grade ≥2 within 3 months prior to enrollment, unless precipitated by an inciting event.
* History of clinically significant cardiovascular disease, or clinically significant abnormalities in rhythm or conduction during Screening ECG, including:

  1. QT corrected by the Fridericia method (QTcF) \> 480 msec within 30 days prior to enrollment; if QTcF is thought to be prolonged due to a modifiable factor (e.g., medication / electrolyte abnormality), QTcF may be re-evaluated
  2. Severe cardiac event (CTCAE grade ≥3) within 3 months prior to enrollment
  3. Heart failure resulting in limitations during ordinary activity.
* Arterial or venous thrombotic or embolic events, including deep vein thrombosis, pulmonary embolism, and cerebrovascular accident (including transient ischemic attacks), within 60 days prior to enrollment.
* Moderate or severe hepatic impairment that meets criteria for Child-Pugh Class B or C, or active viral hepatitis.
* Uncontrolled human immunodeficiency virus (HIV) off antiretrovirals, or on antiretrovirals with detectable viral load.
* Positive Quantiferon (or other interferon gamma release assay) during Screening.
* Known history of disseminated mycobacterial infection.
* Concurrent enrollment in another interventional trial, or treatment with an experimental therapy within 28 days or five half-lives prior to enrollment, whichever is longer.
* Pregnant, intending to become pregnant during the trial, or currently breastfeeding/lactating.
* Participants with any acute, active infection requiring systemic antimicrobial treatment at the time of enrollment. Exceptions are made for prophylactic antibiotics or chronic antibiotic therapy for non-acute conditions.
* Known hypersensitivity to pacritinib or any of the following inactive ingredients: microcrystalline cellulose, polyethylene glycol, and magnesium stearate.

Where this trial is running

Scottsdale, Arizona and 38 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions VEXASVEXAS SyndromeVacuolesE1 Ubiquitin-activating enzymeX-linkedAutoinflammatorySomatic syndromeUBA1
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.