VEXASPhase 2NCT06782373
A Study to Assess the Effectiveness and Safety of Pacritinib in Patients With VEXAS Syndrome (PAXIS)
A Phase 2 study testing Pacritinib in people with VEXAS and VEXAS Syndrome, run by Swedish Orphan Biovitrum at 39 sites in 8 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- VEXAS, VEXAS Syndrome
- What is being tested?
- Pacritinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 156 participants
- Where
- 39 sitesin 8 countries
- Study dates
- 28 May 2025to 22 May 2030
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 16Show fewer
- 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.
Who cannot join
- 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.
Show all 24Show fewer
- 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:
- 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.
- 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 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.
- 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.
Trial locations and contacts
39 sites in 8 countries. Contact the study team or a site near you to ask about taking part.
39 sites in 8 countries
United States9 sites, 1 recruiting
- Active, not recruiting
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
- Active, not recruiting
Cleveland Clinic - Cleveland
Cleveland, Ohio, 44195
- Active, not recruiting
The James Cancer Hospital and Solove Research Institute
Columbus, Ohio, 43210
- Active, not recruiting
UT MD Anderson Cancer Center
Houston, Texas, 77030
- Active, not recruiting
NYU Langone Health
New York, New York, 10016
- Recruiting
Mayo Clinic - Rochester
Rochester, Minnesota, 55905
- Active, not recruiting
University of Utah Healthcare
Salt Lake City, Utah, 84132
- Active, not recruiting
Mayo Clinic - Scottsdale
Scottsdale, Arizona, 85259
- Active, not recruiting
Fred Hutchinson Cancer Center
Seattle, Washington, 98109
France6 sites
- Active, not recruiting
Lille University Hospital Center
Lille, 59037
- Active, not recruiting
Saint-Antoine Hospital - APHP
Paris, 75012
- Active, not recruiting
Tenon Hospital - APHP
Paris, 75020
- Active, not recruiting
Hospices Civils de Lyon - Lyon Sud
Pierre-Bénite, 69310
- Active, not recruiting
University Hospital Center of Poitiers
Poitiers, 86000
- Active, not recruiting
IUCT-Oncopole
Toulouse, 31100
Germany6 sites
- Active, not recruiting
University Hospital Carl Gustav Carus Dresden, Medical Clinic and Polyclinic I
Dresden, Saxony, 01307
- Active, not recruiting
University Hospital Duesseldorf
Düsseldorf, North Rhine-Westphalia, 40225
- Active, not recruiting
University Hospital Hamburg-Eppendorf
Hamburg, Free and Hanseatic City of Hamburg, 20246
- Active, not recruiting
University Hospital Schleswig-Holstein
Lübeck, Schleswig-Holstein, 23538
- Active, not 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
- Active, not recruiting
University Hospital Tuebingen, Medical Clinic II, Hematology, Oncology, Clinical Immunology and Rheumatology
Tübingen, Baden-Wurttemberg, 72076
Canada4 sites, 1 recruiting
- Recruiting
Queen Elizabeth II Health Sciences Center
Halifax, Nova Scotia, B3H 2Y9
- Active, not recruiting
Hospital du Sacre-Coeur in Montreal
Montreal, Quebec, H4J 1C5
- Active, not recruiting
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9
- Active, not recruiting
Vancouver Coastal Health Research Institute
Vancouver, British Columbia, V5Z 1M9
Italy4 sites
- Active, not recruiting
Hospital San Raffaele, IRCCS, Unit of Immunology, Rheumatology, Allergy and Rare Diseases
Milan, 20132
- Active, not recruiting
University Hospital of Padova, Rheumatology Unit, Department of Medicine - DIMED
Padova, 35128
- Active, not recruiting
AUSL of Reggio Emilia - Hospital Arcispedale S. Maria Nuova, Complex Structure of Rheumatology
Reggio Emilia, 42123
- Active, not recruiting
Foundation PTV - Polyclinic Tor Vergata Biomedicine and prevention
Roma, 00133
United Kingdom4 sites
- Active, not recruiting
St James's University Hospital
Leeds, LS9 7TF
- Active, not recruiting
Royal Free Hospital
London, NW3 2QG
- Active, not recruiting
King's College Hospital, Department of Hematology
London, SE5 9RS
- Active, not recruiting
Churchill Hospital
Oxford, OX3 7LE
Japan3 sites
- Active, not recruiting
Fukushima Medical University Hospital
Fukushima, 960-1295
- Active, not recruiting
Nagasaki University Hospital
Nagasaki, 852-8501
- Active, not recruiting
Yokohama City University Hospital
Yokohama, 236-0004
Spain3 sites
- Active, not recruiting
Hospital Clinic of Barcelona
Barcelona, 08036
- Active, not recruiting
Catalan Institute of Oncology, Hospital Duran i Reynals, Department of Clinical Hematology
L'Hospitalet de Llobregat, 08908
- Active, not recruiting
University Clinical Hospital of Salamanca
Salamanca, 37007
About this study
Official title: 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.
Read the detailed description
This trial is a randomized, multicenter, double-blind, placebo-controlled phase 2a and 2b trial 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).
In phase 2a, 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.
In Phase 2b, approximately 78 participants will be randomized (enrollment starts after completion of Phase 2a enrollment). Randomization will initially be conducted in a 1:1:1 ratio to receive pacritinib dose A, pacritinib dose B plus placebo, or placebo, consistent with Phase 2a. Following Phase 2a results, a single pacritinib dose will be selected for continued evaluation. After dose selection, Phase 2b further participants will be randomized in a 2:1 ratio of the selected pacritinib dose to placebo until the total target of 78 participants are randomized.
Randomization will be stratified by prescribed GC dose on the day of randomization. All outcomes will be reported by treatment arm, and comparisons between each pacritinib arm and placebo (Phase 2a) or between the selected pacritinib dose and placebo (Phase 2b) will be performed in the double-blind treatment periods.
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 in Phase 2a or due to dose selection in Phase 2b), all participants currently randomized to the terminated arm will transition to open-label treatment.
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 2 years on the extension period. Participants who discontinue study treatment will have a 30-day post-End of Treatment (EOT) follow-up period.
The trial (including the double-blind and open-label treatment periods, as well as the extension period) is planned to end approximately 3 years from the first dose of the last participant.
- Conditions
- VEXAS, VEXAS Syndrome
- Being tested
- Pacritinib, Placebo
- Keywords
- Vacuoles, E1 Ubiquitin-activating enzyme, X-linked, Autoinflammatory, Somatic syndrome, UBA1, Hematologic neoplasms, Myelodysplastic Syndromes, Pacritinib, Myeloid progenitors
- Medical subject headings
- VEXAS syndrome, Hematologic Neoplasms, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PacritinibDrug
Supplied in hard capsules.
PlaceboDrug
Supplied in hard capsules.
| Study group | Role | What they receive |
|---|---|---|
| Pacritinib | Experimental | To receive oral administration of pacritinib dose A for up to 24 weeks. Receives: Drug: Pacritinib |
| Pacritinib + placebo | Experimental | To receive oral administration of pacritinib dose B plus placebo for up to 24 weeks Receives: Drug: Pacritinib; Drug: Placebo |
| Placebo | Placebo comparator | To receive oral administration of placebo for up to 24 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR), defined as achieving Partial Clinical Response or better at any time during the double-blind treatment period.
Difference in the proportion of participants achieving ORR for the pairwise comparison of pacritinib dose A vs. placebo and pacritinib dose B plus placebo vs. placebo (Phase 2a) and selected pacritinib dose compared to placebo (Phase 2b)
Measured: up to End of Week 24
Secondary outcomes (14)
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 (Phase 2a) and selected pacritinib dose compared to placebo (Phase 2b)
Measured: up to End of Week 24
Number of flare-free days with GC dose ≤10 mg
Measured: up to End of Week 24
Proportion of participants on each arm achieving each Best Response category (Clinical Biochemical Response, Clinical Response, Partial Clinical Response, Stable Disease, or Non-response).
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: up to Week 24 (pre-dose only)
Change in pharmacodynamic (PD) inflammatory biomarker: C-reactive protein (CRP)
Measured: up to 30-day Post-End of Trial
Change in PD inflammatory biomarker: erythrocyte sedimentation rate (ESR)
Measured: up to 30-day Post-End of Trial
Change in PD inflammatory biomarker: ferritin
Measured: up to 30-day Post-End of Trial
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2025
- Study start28 May 2025
- Primary completion30 Dec 2026 (estimated)
- Study completion22 May 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for VEXASStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- In phase 2a, 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 the double-blind treatment period. In phase 2b, participants will be randomized initially in a 1:1:1 ratio to receive pacritinib dose A, pacritinib dose B plus placebo, or placebo, consistent with Phase 2a. Following Phase 2a results, a single pacritinib dose will be selected for continued evaluation. After dose selection, Phase 2b further participants will be randomized in a 2:1 ratio of the selected pacritinib dose to placebo during the double-blind treatment period. Randomization will be stratified by prescribed GC dose on the day of randomization.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 156 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Swedish Orphan Biovitrum
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- PSI CRO
- Responsible party
- Sponsor
- Investigators
- Study Physician, Study director, Sobi, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06782373
- Sponsor's protocol ID
- PAC601
- Other IDs
- 2024-516347-41-00
- Status last verified
- Oct 2026
- First submitted
- 7 Jan 2025
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
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.
PubMed 41753113