A Study to Assess the Effectiveness and Safety of Pacritinib in Patients With VEXAS Syndrome (PAXIS)

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

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. 78 participants will be enrolled, randomized to either pacritinib dose A, pacritinib dose B + placebo, or placebo. Randomization will be stratified by prescribed GC dose on the day of randomization.

Study Overview

• Status: Recruiting
• Conditions: VEXAS Syndrome; VEXAS
• Intervention / Treatment: Drug: Pacritinib; Drug: Placebo

Detailed Description

This trial is a randomized, multicenter, double-blind, placebo-controlled phase 2 trial (Part 1) followed by an open-label treatment period (Part 2) designed to evaluate the efficacy and safety of pacritinib for the prevention of VEXAS flares after glucocorticoid (GC) taper. The trial will enroll participants ≥18 years with inflammatory VEXAS syndrome receiving ongoing GC therapy for ≥4 consecutive weeks, requiring between 15 and 45 mg daily (of prednisone / prednisolone or equivalent) at the time of enrollment (randomization). Participants will be randomized 1:1:1 to receive pacritinib dose A (n=26), pacritinib dose B plus placebo (n=26), or placebo (n=26) for up to 24 weeks during a double-blind treatment period, followed by treatment with pacritinib during an open-label treatment period for up to 48 weeks. Participants who complete the open-label treatment period at End of Week (EOW) 48 and who are benefitting from pacritinib in the opinion of the Investigator may continue to receive treatment for an additional 1 year on the extension period. Participants who discontinue study treatment will have a 30-day post-End of Treatment (EOT) follow-up period. Randomization will be stratified by prescribed GC dose on the day of randomization. All outcomes will be reported by treatment arm, and pair-wise comparison between each pacritinib arm and placebo will be performed in the double-blind treatment period.

Participants who complete the double-blind treatment period at EOW 24 or meet Early Failure criteria at EOW 12 will transition to an open-label pacritinib treatment period through EOW 48. In addition, if a trial arm closes due to interim futility or safety, all participants currently randomized to that arm will transition to open-label treatment.

The trial (including the double-blind and open-label treatment periods, as well as the extension period) is planned to end approximately 2 years from the first dose of the last participant.

• Study Type: Interventional
• Enrollment (Estimated): 78
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Study Physician; Phone Number: +4686972000; Email: medical.info@sobi.com

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Recruiting
      • Vancouver Coastal Health Research Institute
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Recruiting
      • Queen Elizabeth II Health Sciences Center
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Recruiting
      • Princess Margaret Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H4J 1C5
      • Recruiting
      • Hospital du Sacre-Coeur in Montreal
• France
  • Lille, France, 59037
    • Recruiting
    • Lille University Hospital Center
  • Paris, France, 75012
    • Recruiting
    • Saint-Antoine Hospital - APHP
  • Paris, France, 75020
    • Recruiting
    • Tenon Hospital - APHP
  • Pierre-Bénite, France, 69310
    • Recruiting
    • Hospices Civils de Lyon - Lyon Sud
  • Poitiers, France, 86000
    • Recruiting
    • University Hospital Center of Poitiers
  • Toulouse, France, 31100
    • Recruiting
    • IUCT-Oncopole
• Germany
  • Baden-Wurttemberg
    • Tübingen, Baden-Wurttemberg, Germany, 72076
      • Recruiting
      • University Hospital Tuebingen, Medical Clinic II, Hematology, Oncology, Clinical Immunology and Rheumatology
  • Bavaria
    • Munich, Bavaria, Germany, 81675
      • Recruiting
      • Hospital Rechts der Isar of the Technical University of Munich, Clinic and Polyclinic for Internal Medicine III: Hematology and Internal Oncology
  • Free and Hanseatic City of Hamburg
    • Hamburg, Free and Hanseatic City of Hamburg, Germany, 20246
      • Recruiting
      • University Hospital Hamburg-Eppendorf
  • North Rhine-Westphalia
    • Düsseldorf, North Rhine-Westphalia, Germany, 40225
      • Recruiting
      • University Hospital Duesseldorf
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Recruiting
      • University Hospital Carl Gustav Carus Dresden, Medical Clinic and Polyclinic I
  • Schleswig-Holstein
    • Lübeck, Schleswig-Holstein, Germany, 23538
      • Recruiting
      • University Hospital Schleswig-Holstein
• Italy
  • Milan, Italy, 20132
    • Recruiting
    • Hospital San Raffaele, IRCCS, Unit of Immunology, Rheumatology, Allergy and Rare Diseases
  • Padova, Italy, 35128
    • Recruiting
    • University Hospital of Padova, Rheumatology Unit, Department of Medicine - DIMED
  • Reggio Emilia, Italy, 42123
    • Recruiting
    • AUSL of Reggio Emilia - Hospital Arcispedale S. Maria Nuova, Complex Structure of Rheumatology
  • Roma, Italy, 00133
    • Recruiting
    • Foundation PTV - Polyclinic Tor Vergata Biomedicine and prevention
• Japan
  • Fukushima, Japan, 960-1295
    • Recruiting
    • Fukushima Medical University Hospital
  • Nagasaki, Japan, 852-8501
    • Recruiting
    • Nagasaki University Hospital
  • Yokohama, Japan, 236-0004
    • Recruiting
    • Yokohama City University Hospital
• Spain
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clinic of Barcelona
  • L'Hospitalet de Llobregat, Spain, 08908
    • Recruiting
    • Catalan Institute of Oncology, Hospital Duran i Reynals, Department of Clinical Hematology
  • Salamanca, Spain, 37007
    • Recruiting
    • University Clinical Hospital of Salamanca
• United Kingdom
  • Leeds, United Kingdom, LS9 7TF
    • Recruiting
    • St James's University Hospital
  • London, United Kingdom, NW3 2QG
    • Recruiting
    • Royal Free Hospital
  • London, United Kingdom, SE5 9RS
    • Recruiting
    • King's College Hospital, Department of Hematology
  • Oxford, United Kingdom, OX3 7LE
    • Recruiting
    • Churchill Hospital
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Recruiting
      • Mayo Clinic - Scottsdale
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic - Rochester
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Health
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic - Cleveland
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • The James Cancer Hospital and Solove Research Institute
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • UT MD Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Recruiting
      • University of Utah Healthcare
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Fred Hutchinson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pacritinib; To receive oral administration of pacritinib dose A for up to 24 weeks.	Drug: Pacritinib; Supplied in hard capsules.
Experimental: Pacritinib + placebo; To receive oral administration of pacritinib dose B plus placebo for up to 24 weeks	Drug: Pacritinib; Supplied in hard capsules.; Drug: Placebo; Supplied in hard capsules.
Placebo Comparator: Placebo; To receive oral administration of placebo for up to 24 weeks.	Drug: Placebo; Supplied in hard capsules.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Clinical Response (OCR), defined as achieving Clinical Response or better at any time during the double-blind treatment period.	Difference in the proportion of participants achieving OCR for the pairwise comparison of pacritinib dose A vs. placebo and pacritinib dose B plus placebo vs. placebo	up to End of Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of flare-free days with GC dose <10 mg		up to End of Week 24
Change in health-related quality of life (QOL) as measured by Patient-Reported Outcomes Measurement Information Systems (PROMIS) fatigue short form	The PROMIS short form domains of fatigue 4a will be summarized, raw score from 4 to 20 (T-score from 33.7 to 75.8). A higher score is associated with more fatigue.	up to End of Week 24
Change in health-related QOL as measured by PROMIS physical function short form	The PROMIS short form domains of physical function 4a will be summarized, raw score from 4 to 20 (T-score from 22.5 to 57.0). A higher score is associated with better physical function.	up to End of Week 24
Change in health-related QOL as measured by PROMIS sleep disturbance short form	The PROMIS short form domains of sleep disturbance 4a will be summarized, raw score from 4 to 20 (T-score from 32.0 to 73.3). A higher score is associated with more sleep disturbance.	up to End of Week 24
Change in health-related QOL as measured by the 36-item short form (SF) Survey	The SF-36 Survey measures eight domains of health status; physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-being, social functioning, pain, and general health. The values for each domain range from 0 to 100, with the higher score indicating a better health status.	up to End of Week 24
Mean plasma concentration of pacritinib	Mean plasma concentrations (pre-dose and post-dose) will be determined for each pharmacokinetic sampling timepoint.	up to Week 24 (pre-dose only)
Change in pharmacodynamic (PD) inflammatory biomarker: C-reactive protein (CRP)		up to 30-day Post-End of Trial
Change in PD inflammatory biomarker: erythrocyte sedimentation rate (ESR)		up to 30-day Post-End of Trial
Change in PD inflammatory biomarker: ferritin		up to 30-day Post-End of Trial
Proportion of participants on each arm achieving each Best Response category (Clinical Biochemical Response, Clinical Response, Partial Clinical Response, Stable Disease, or Non-response).		up to End of Week 24
Hematologic Improvement - Erythroid	Erythroid (HI-E) at any time among participants with baseline hemoglobin <10 g/dL per modified International Working Group (IWG) criteria	up to End of Week 24
Hematologic Improvement - Platelets	Platelets (HI-P) at any time among participants with baseline platelet count <100 × 10^9/L per modified IWG criteria	up to End of Week 24
Change in health-related QOL as measured by Patient's Global Impression of Change (PGIC) response	The number and percentage of participants achieving PGIC response (reporting symptoms as "much" or "very much" improved).	up to End of Week 24

Collaborators and Investigators

• Sponsor: Swedish Orphan Biovitrum
• Collaborators: PSI CRO
• Investigators: Study Director: Study Physician, Sobi, Inc.

Publications and helpful links

General Publications

• Beck DB, Heiblig M, Savic S, Ferrada MA, Mekinian A, Chowdhury O, Hammond D, Weeks LD, Gurnari C, Kirino Y, Georgin-Lavialle S, Buckley SA, Garcha R, Harder BG, Koster MJ. 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. J Clin Med. 2026 Feb 11;15(4):1426. doi: 10.3390/jcm15041426.

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2025
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): May 22, 2028

Study Registration Dates

• First Submitted: January 7, 2025
• First Submitted That Met QC Criteria: January 14, 2025
• First Posted (Actual): January 17, 2025

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Myelodysplastic Syndromes; X-linked; Pacritinib; Autoinflammatory; Hematologic neoplasms; UBA1; Vacuoles; E1 Ubiquitin-activating enzyme; Somatic syndrome; Myeloid progenitors
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Hematologic Diseases; Bone Marrow Diseases; Hemic and Lymphatic Diseases; Hematologic Neoplasms; Myelodysplastic Syndromes; VEXAS syndrome; Substandard Drugs; Pharmaceutical Preparations; 11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene
• Other Study ID Numbers: PAC601; 2024-516347-41-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related trial documents. Patient level data will be anonymized and trial documents, if applicable will be redacted to protect the privacy of trial participants.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No