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

NCT ID: NCT06782373

Last Updated: 2025-12-22

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 78 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-28
• Study Completion Date: 2028-05-22

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.

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.

Conditions

VEXAS; VEXAS Syndrome

Keywords

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Pacritinib

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

Group Type: EXPERIMENTAL

Pacritinib

Intervention Type: DRUG

Supplied in hard capsules.

Pacritinib + placebo

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

Group Type: EXPERIMENTAL

Pacritinib

Intervention Type: DRUG

Supplied in hard capsules.

Placebo

Intervention Type: DRUG

Supplied in hard capsules.

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Supplied in hard capsules.

Interventions

Pacritinib

Supplied in hard capsules.

Intervention Type: DRUG

Placebo

Supplied in hard capsules.

Intervention Type: DRUG

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PSI CRO

INDUSTRY

Sponsor Role: collaborator

Swedish Orphan Biovitrum

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Physician

Role: STUDY_DIRECTOR

Sobi, Inc.

Locations

Mayo Clinic - Scottsdale

Scottsdale, Arizona, United States

University of Maryland Medical Center Midtown Campus

Baltimore, Maryland, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Mayo Clinic - Rochester

Rochester, Minnesota, United States

NYU Langone Health

New York, New York, United States

Cleveland Clinic - Cleveland

Cleveland, Ohio, United States

The James Cancer Hospital and Solove Research Institute

Columbus, Ohio, United States

UT MD Anderson Cancer Center

Houston, Texas, United States

University of Utah Healthcare

Salt Lake City, Utah, United States

Fred Hutchinson Cancer Center

Seattle, Washington, United States

Vancouver Coastal Health Research Institute

Vancouver, British Columbia, Canada

Queen Elizabeth II Health Sciences Center

Halifax, Nova Scotia, Canada

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Hospital du Sacre-Coeur in Montreal

Montreal, Quebec, Canada

Lille University Hospital Center

Lille, , France

Saint-Antoine Hospital - APHP

Paris, , France

Tenon Hospital - APHP

Paris, , France

Hospices Civils de Lyon - Lyon Sud

Pierre-Bénite, , France

University Hospital Center of Poitiers

Poitiers, , France

IUCT-Oncopole

Toulouse, , France

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

Tübingen, Baden-Wurttemberg, Germany

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

Munich, Bavaria, Germany

University Hospital Hamburg-Eppendorf

Hamburg, Hamburg, Germany

University Hospital Duesseldorf

Düsseldorf, North Rhine-Westphalia, Germany

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

Dresden, Saxony, Germany

University Hospital Schleswig-Holstein

Lübeck, Schleswig-Holstein, Germany

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

Milan, , Italy

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

Padua, , Italy

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

Reggio Emilia, , Italy

Foundation PTV - Polyclinic Tor Vergata Biomedicine and prevention

Roma, , Italy

Fukushima Medical University Hospital

Fukushima, , Japan

Nagasaki University Hospital

Nagasaki, , Japan

Yokohama City University Hospital

Yokohama, , Japan

Hospital Clinic of Barcelona

Barcelona, , Spain

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

L'Hospitalet de Llobregat, , Spain

University Clinical Hospital of Salamanca

Salamanca, , Spain

St James's University Hospital

Leeds, , United Kingdom

Royal Free Hospital

London, , United Kingdom

King's College Hospital, Department of Hematology

London, , United Kingdom

Churchill Hospital

Oxford, , United Kingdom

Countries

United States; Canada; France; Germany; Italy; Japan; Spain; United Kingdom

Other Identifiers

2024-516347-41-00

Identifier Type: CTIS

Identifier Source: secondary_id

PAC601

Identifier Type: -

Identifier Source: org_study_id