Tests pacritinib in adults with VEXAS syndrome, a rare inflammatory disease

Trial details

Who runs it

Swedish Orphan Biovitrum

Trial code

NCT06782373EU 2024-516347-41-00

Record updated

16 October 2026

Original description

This trial is to assess the effectiveness and safety of pacritinib in patients with VEXAS (i.e., Vacuoles in myeloid progenitors, E1 ubiquitin-activating enzyme, X-linked, autoinflammatory manifestations, and somatic) syndrome. In phase 2a, approximately 78 participants will be randomized to either pacritinib dose A, pacritinib dose B + placebo, or placebo. In Phase 2b, approximately 78 participants will be randomized. Phase 2b participants will initially be randomized to either pacritinib dose A, pacritinib dose B + placebo, or placebo. After dose selection, Phase 2b further participants will be randomized to either the selected pacritinib dose or placebo.Read full original descriptionShow less

PAXIS: A Phase 2a and 2b Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Pacritinib in Patients With VEXAS Syndrome

This trial is to assess the effectiveness and safety of pacritinib in patients with VEXAS (i.e., Vacuoles in myeloid progenitors, E1 ubiquitin-activating enzyme, X-linked, autoinflammatory manifestations, and somatic) syndrome. In phase 2a, approximately 78 participants will be randomized to either pacritinib dose A, pacritinib dose B + placebo, or placebo. In Phase 2b, approximately 78 participants will be randomized. Phase 2b participants will initially be randomized to either pacritinib dose A, pacritinib dose B + placebo, or placebo. After dose selection, Phase 2b further participants will be randomized to either the selected pacritinib dose or placebo.

Randomization will be stratified by prescribed GC dose on the day of randomization.

Inclusion: 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:; Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × upper limit of normal (ULN); Total bilirubin ≤4 × ULN (≤8 × ULN in the setting of Gilbert's syndrome); Creatinine clearance (CrCl) ≥30 mL/min based on the Cockcroft-Gault formula; Absolute neutrophil count ≥500/μL; Prothrombin time (PT) or international normalized ratio (INR) ≤1.5 × ULN (unless prolonged due to therapeutic anticoagulation); Partial thromboplastic time (PTT) or activated PTT ≤1.5 × ULN (unless prolonged due to therapeutic anticoagulation); Platelet count ≥25 × 10\^9/L (value must be obtained in the absence of platelet transfusion in the prior 7 days); 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. Participants with ventricular paced rhythms may enroll if their QTcF is ≤500 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.

Exclusion: Prior allogenic hematopoietic stem cell transplant (allo-HSCT) or solid organ transplant (other than corneal); 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; 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:; Severe cardiac event (CTCAE grade ≥3) within 3 months prior to enrollment; 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; Concurrent or prior enrollment in another prospective interventional trial of VEXAS-directed therapy, or concurrent enrollment in another interventional trial of non-VEXAS-directed therapy, or treatment with a non-VEXAS-directed experimental therapy within 28 days or five half-lives prior to enrollment, whichever is longer; 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; 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; Known history of disseminated mycobacterial infection; 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; 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; Known hypersensitivity to pacritinib or any of the following inactive ingredients: microcrystalline cellulose, polyethylene glycol, and magnesium stearate; Positive Quantiferon (or other interferon gamma release assay) during Screening; Pregnant, intending to become pregnant during the trial, or currently breastfeeding/lactating.

ClinicalTrials.gov NCT06782373 · EU CTIS 2024-516347-41-00