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NCT06782373 | NOT YET RECRUITING | VEXAS

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

Swedish Orphan Biovitrum

Brief Summary:

This study 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 patients 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.

Condition or disease

See

Cough

Intervention/treatment

Pacritinib

Placebo

Phase

PHASE2

Detailed Description:

This study is a randomized, multicenter, double-blind, placebo-controlled phase 2 study (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 study will enroll patients ≥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). Patients 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, and 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. Patients who complete the double-blind treatment period at End of Week 24 or meet Early Failure criteria at End of Week 12 will transition to an open-label pacritinib treatment period through End of Week 48. In addition, if a study arm closes due to interim futility or safety, all patients currently randomized to that arm will transition to open-label treatment. Study termination is planned approximately 1 year from the first dose of the last patient.

Study Type : INTERVENTIONAL
Estimated Enrollment : 78 participants
Masking : TRIPLE
Masking Description : In the double-blind portion of the study, the Sponsor, study patients, 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.
Primary Purpose : TREATMENT
Official Title : 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
Actual Study Start Date : 2025-05
Estimated Primary Completion Date : 2027-08
Estimated Study Completion Date : 2027-08

Information not available for Arms and Intervention/treatment

Ages Eligible for Study: 18 Years
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers:
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 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. Note that patients who are stable on GC doses of 10-14 mg/day in addition to another non-GC anti-inflammatory therapy at Screening who have a previously documented VEXAS flare on a GC dose \>=10mg/day may be eligible provided that their GC dose is escalated to 15-45 mg/day after washout.
  • * 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
    • 8. Peripheral blasts \<5%
    • * 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 patients must agree to use a highly effective method of contraception starting at the first dose of study therapy through 90 days after the last dose of study 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). Patients 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. Patients 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 4 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. Patients 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 study, 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 study, or currently breastfeeding/lactating.
      • * Patients 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.
A Study to Assess the Effectiveness and Safety of Pacritinib in Patients With VEXAS Syndrome (PAXIS)

Location Details

NCT06782373

Please Choose a site

How to Participate

Want to participate in this study, select a site at your convenience, send yourself email to get contact details and prescreening steps.

Locations

Not yet recruiting

United States, Arizona

Mayo Clinic - Scottsdale

Scottsdale, Arizona, United States, 85259

Not yet recruiting

United States, Maryland

University of Maryland Medical Center Midtown Campus

Baltimore, Maryland, United States, 21201

Not yet recruiting

United States, Massachusetts

Dana Farber Cancer Institute

Boston, Massachusetts, United States, 02215

Not yet recruiting

United States, Minnesota

Mayo Clinic - Rochester

Rochester, Minnesota, United States, 55905

Not yet recruiting

United States, New York

NYU Langone Health

New York, New York, United States, 10016

Not yet recruiting

United States, Ohio

Cleveland Clinic - Cleveland

Cleveland, Ohio, United States, 44195

Not yet recruiting

United States, Ohio

The James Cancer Hospital and Solove Research Institute

Columbus, Ohio, United States, 43210

Not yet recruiting

United States, Texas

UT MD Anderson Cancer Center

Houston, Texas, United States, 77030

Not yet recruiting

United States, Utah

University of Utah Healthcare

Salt Lake City, Utah, United States, 84132

Not yet recruiting

United States, Washington

Fred Hutchinson Cancer Center

Seattle, Washington, United States, 98109

Not yet recruiting

Canada, British Columbia

Vancouver Coastal Health Research Institute

Vancouver, British Columbia, Canada, V5Z 1M9

Not yet recruiting

Canada, New Scotia

Queen Elizabeth II Health Sciences Center

Halifax, Nova Scotia, Canada, He was cut off

Not yet recruiting

Canada, Ontario

Princess Margaret Cancer Centre

Toronto, Ontario, Canada, M5G 2M9

Not yet recruiting

Canada, Quebec

Sacre-Coeur Hospital in Montreal

Montréal, Quebec, Canada, H4J 1C5

Not yet recruiting

France,

Lille University Hospital Center

Lille, France, 59037

Not yet recruiting

France,

Saint-Antoine Hospital - APHP

Paris, France, 75012

Not yet recruiting

France,

Tenon Hospital - APHP

Paris, France, 75020

Not yet recruiting

France,

Civil Hospices in Lyon - Lyon Sud

Pierre-Bénite, France, 69310

Not yet recruiting

France,

University Hospital Center of Poitiers

Poitiers, France, 86000

Not yet recruiting

France,

IUCT-Oncopole

Toulouse, France, 31100

Not yet recruiting

Germany, Baden-Wuerttemberg

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

Tue, Baden-Wuerttemberg, Germany, 72076

Not yet recruiting

Germany, Bavaria

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

Munich, Bavaria, Germany, 81675

Not yet recruiting

Germany, North Rhine-Westphalia

University Hospital Duesseldorf

Duesseldorf, North Rhine-Westphalia, Germany, 40225

Not yet recruiting

Germany, Saxony

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

Dresden, Saxony, Germany, 01307

Not yet recruiting

Germany, Schleswig-Holstein

University Hospital Schleswig-Holstein

Luebeck, Schleswig-Holstein, Germany, 23538

Not yet recruiting

Germany,

University Hospital Hamburg-Eppendorf

Hamburg, Germany, 20246

Not yet recruiting

Italy,

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

Milan, Italy, 20132

Not yet recruiting

Italy,

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

Padova, Italy, 35128

Not yet recruiting

Italy,

AUSL OF REGGIO EMILIA - HOSPITAL ARCISLANDO S. Maria NEW, Complex Structure of Rheumatology

Reggio Emilia, Italy, 42123

Not yet recruiting

Italy,

Foundation PTV - Polyclinic Tor Vergata Biomedicine and prevention

Roma, Italy, 00133

Not yet recruiting

Japan,

Fukushima Medical University Hospital

Fukushima, Japan, 960-1295

Not yet recruiting

Japan,

Nagasaki University Hospital

Nagasaki, Japan, 852-8501

Not yet recruiting

Japan,

Yokohama City University Hospital

Yokohama, Japan, 236-0004

Not yet recruiting

Spain,

Hospital Clinic of Barcelona

Barcelona, Spain, 08036

Not yet recruiting

Spain,

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

Hospitalet de Llobregat, Spain, 08908

Not yet recruiting

Spain,

University Clinical Hospital of Salamanca

Salamanca, Spain, 37007

Not yet recruiting

United Kingdom,

St James's University Hospital

Leeds, United Kingdom, LS9 7TF

Not yet recruiting

United Kingdom,

Royal Free Hospital

London, United Kingdom, Drainage

Not yet recruiting

United Kingdom,

King's College Hospital, Department of Hematology

London, United Kingdom, SE5 9RS

Not yet recruiting

United Kingdom,

Churchill Hospital

Oxford, United Kingdom, As a solution