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

NCT06782373 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: PAC6012024-516347-41-00
• Study Type: interventional
• Target: 78
• Locations: 8 countries
• Sites: 39

Brief Summary

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.

Conditions

VEXAS; VEXAS Syndrome

Keywords

Vacuoles; E1 Ubiquitin-activating enzyme; X-linked; Autoinflammatory; Somatic syndrome; UBA1; Hematologic neoplasms; Myelodysplastic Syndromes; Pacritinib; Myeloid progenitors

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (13)

• 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

• Number of flare-free days with GC dose <10 mg

  up to End of Week 24

• Hematologic Improvement - Erythroid

  up to End of Week 24

• Hematologic Improvement - Platelets

  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

  up to End of Week 24

Study Arms (3)

Pacritinib

EXPERIMENTAL

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

Drug: Pacritinib

Pacritinib + placebo

EXPERIMENTAL

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

Drug: Pacritinib; Drug: Placebo

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Pacritinib DRUG

Supplied in hard capsules.

Pacritinib; Pacritinib + placebo

Placebo DRUG

Supplied in hard capsules.

Pacritinib + placebo; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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. 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.

You may not qualify if:

• 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.
• 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:
• 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
• Severe cardiac event (CTCAE grade ≥3) within 3 months prior to enrollment
• Heart failure resulting in limitations during ordinary activity.

Sponsors & Collaborators

• PSI CRO: collaborator
• Swedish Orphan Biovitrum: lead

Study Sites (39)

Mayo Clinic - Scottsdale

Scottsdale, Arizona, 85259, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

NYU Langone Health

New York, New York, 10016, United States

RECRUITING

Cleveland Clinic - Cleveland

Cleveland, Ohio, 44195, United States

RECRUITING

The James Cancer Hospital and Solove Research Institute

Columbus, Ohio, 43210, United States

RECRUITING

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

University of Utah Healthcare

Salt Lake City, Utah, 84132, United States

RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

Vancouver Coastal Health Research Institute

Vancouver, British Columbia, V5Z 1M9, Canada

RECRUITING

Queen Elizabeth II Health Sciences Center

Halifax, Nova Scotia, B3H 2Y9, Canada

RECRUITING

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

Hospital du Sacre-Coeur in Montreal

Montreal, Quebec, H4J 1C5, Canada

RECRUITING

Lille University Hospital Center

Lille, 59037, France

RECRUITING

Saint-Antoine Hospital - APHP

Paris, 75012, France

RECRUITING

Tenon Hospital - APHP

Paris, 75020, France

RECRUITING

Hospices Civils de Lyon - Lyon Sud

Pierre-Bénite, 69310, France

RECRUITING

University Hospital Center of Poitiers

Poitiers, 86000, France

RECRUITING

IUCT-Oncopole

Toulouse, 31100, France

RECRUITING

University Hospital Tuebingen, Medical Clinic II, Hematology, Oncology, Clinical Immunology and Rheumatology

Tübingen, Baden-Wurttemberg, 72076, Germany

RECRUITING

Hospital Rechts der Isar of the Technical University of Munich, Clinic and Polyclinic for Internal Medicine III: Hematology and Internal Oncology

Munich, Bavaria, 81675, Germany

RECRUITING

University Hospital Hamburg-Eppendorf

Hamburg, Free and Hanseatic City of Hamburg, 20246, Germany

RECRUITING

University Hospital Duesseldorf

Düsseldorf, North Rhine-Westphalia, 40225, Germany

RECRUITING

University Hospital Carl Gustav Carus Dresden, Medical Clinic and Polyclinic I

Dresden, Saxony, 01307, Germany

RECRUITING

University Hospital Schleswig-Holstein

Lübeck, Schleswig-Holstein, 23538, Germany

RECRUITING

Hospital San Raffaele, IRCCS, Unit of Immunology, Rheumatology, Allergy and Rare Diseases

Milan, 20132, Italy

RECRUITING

University Hospital of Padova, Rheumatology Unit, Department of Medicine - DIMED

Padova, 35128, Italy

RECRUITING

AUSL of Reggio Emilia - Hospital Arcispedale S. Maria Nuova, Complex Structure of Rheumatology

Reggio Emilia, 42123, Italy

RECRUITING

Foundation PTV - Polyclinic Tor Vergata Biomedicine and prevention

Roma, 00133, Italy

RECRUITING

Fukushima Medical University Hospital

Fukushima, 960-1295, Japan

RECRUITING

Nagasaki University Hospital

Nagasaki, 852-8501, Japan

RECRUITING

Yokohama City University Hospital

Yokohama, 236-0004, Japan

RECRUITING

Hospital Clinic of Barcelona

Barcelona, 08036, Spain

RECRUITING

Catalan Institute of Oncology, Hospital Duran i Reynals, Department of Clinical Hematology

L'Hospitalet de Llobregat, 08908, Spain

RECRUITING

University Clinical Hospital of Salamanca

Salamanca, 37007, Spain

RECRUITING

St James's University Hospital

Leeds, LS9 7TF, United Kingdom

RECRUITING

Royal Free Hospital

London, NW3 2QG, United Kingdom

RECRUITING

King's College Hospital, Department of Hematology

London, SE5 9RS, United Kingdom

RECRUITING

Churchill Hospital

Oxford, OX3 7LE, United Kingdom

RECRUITING

Related Publications (1)

• 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.

  PMID: 41753113 DERIVED

MeSH Terms

Conditions

VEXAS syndrome; Hematologic Neoplasms; Myelodysplastic Syndromes

Interventions

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

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Study Officials

• Study Physician

  Sobi, Inc.

  STUDY DIRECTOR

Central Study Contacts

Study Physician

CONTACT

+4686972000; medical.info@sobi.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: In the double-blind portion of the trial, the Sponsor, trial participants, and Investigators will be blinded to treatment assignments. Active and placebo products will be of identical appearance. The Independent Data Monitoring Committee will have access to unblinded data.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will be randomized 1:1:1 to receive pacritinib dose A, pacritinib dose B plus placebo, or placebo 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. Randomization will be stratified by prescribed GC dose on the day of randomization.

Study Record Dates

• First Submitted: January 7, 2025
• First Posted: January 17, 2025
• Study Start: May 28, 2025
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): May 22, 2028
• Last Updated: April 24, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

JP (3); CA (4); FR (6); US (9); DE (6); IT (4); GB (4); ES (3)