Clinical Trials

Inclusion Criteria: 

• Age ≥ 18 years at the time of signing the ICF.
• Documented evidence of a pathogenic or likely pathogenic mutation at M41 or neighboring splice site mutation (c.118-1, c.118-2) position in UBA1 based on myeloid 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). Note: Other inflammatory signs may be considered for enrollment at the discretion of the Investigator with Medical Monitor approval provided that these signs have been previously demonstrated to be GC-responsive (i.e., resolve after administration of or escalation in GC therapy).
• Receiving ongoing GC therapy (with prednisone or prednisolone) for ≥ 4 consecutive weeks leading up to enrollment for treatment of VEXAS syndrome.
• Prednisone or prednisolone baseline dose of 15-45 mg/day that has been stable for ≥ 10 days prior to enrollment. Note that patients who are stable on GC doses of 10-14 mg daily in addition to another non-GC anti-inflammatory therapy at Screening who have a previously documented VEXAS flare on GC monotherapy at a dose of ≥ 10 mg may be eligible provided that their GC dose is escalated to 15-45 mg daily after washout, and that this dose is stable for ≥ 10 days prior to enrollment.
• Karnofsky Performance Status ≥ 50% (Appendix 3)
• Adequate organ function, meeting all the following criteria within 30 days prior to enrollment:
  • 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 (Appendix 4)
  • Absolute neutrophil count ≥ 500/µL
  • PT or international normalized ratio (INR) ≤ 1.5 × ULN (unless prolonged due to therapeutic anticoagulation)
  • PTT or activated PTT ≤ 1.5 × ULN (unless prolonged due to therapeutic anticoagulation) g. Platelet count ≥ 25 × 109 /L h. Peripheral blasts < 5%
• 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, described in Section 6.4.6.6.
• Willingness and ability of the patient to comply with protocol requirements, including but not limited to: completing in-person study visits, completing training in the use of the Prednisone / Prednisolone Dose Diary and recording daily prednisone or prednisolone dose use in the diary, undergoing study-related procedures, and completing patientreported outcome (PRO) assessments.
• Provision of signed informed consent.

Exclusion Criteria: 

• Prior 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 RBC transfusion in the 90 days prior to enrollment .
• Known concurrent myelodysplastic syndrome (MDS) requiring antineoplastic treatment (e.g., HMAs), or allo-HSCT, or known high-risk or very high-risk MDS based on the Revised International Prognostic Scoring System (IPSS-R) (31). 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. 7. Exposure to HMAs (e.g., azacitidine, decitabine) within 6 months prior to enrollment, or exposure to more than 4 cycles of HMAs at any time.
• Exposure to the following agents within the following timeframe prior to enrollment :
  • Anti-CD20 agents (e.g., rituximab): 180 days
  • Anti-IL-23 agents (e.g., ustekinumab): 90 days
  • Anti-TNFα agents except for etanercept (e.g., infliximab): 60 days
  • Canakinumab: 60 days
  • Intravenous anti-IL-6 agents: 42 days
  • Subcutaneous anti-IL-6 agents: 28 days
  • Anti-IL-17 agents (e.g., secukinumab): 28 days
  • Anti-integrins (e.g., vedolizumab): 60 days
  • Intravenous immunoglobulin: 28 days
  • Danazol, immunomodulatory imide drugs (IMiDs), luspatercept, or thrombopoietin receptor agonists: 28 days
  • Cytotoxic chemotherapy: 28 days l. Etanercept: 21 days
  • Oral JAK inhibitors: 14 days
  • Anti-IL-1 agents except for canakinumab: 14 days
  • Any other non-GC anti-inflammatory therapy (e.g., mycophenolate, azathioprine, cyclosporine, sulfasalazine, methotrexate): 14 days Note: Patients on erythropoiesis stimulating agents (ESAs) at the time of informed consent may continue to receive ESAs during Screening and on study, but new ESA use is not permitted during this 28-day period or on study.
• 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-touninvolved free light chain (FLC) ratio ≥ 100, or involved FLC level ≥100 mg/dL. Patients with MGUS may enroll.
• Systemic treatment with a strong CYP3A4 inhibitor or inducer within 5 half-lives prior to enrollment (Appendix 5).
• Significant recent bleeding history defined as National Cancer Institute CTCAE grade ≥ 2 within 3 months prior to enrollment, unless precipitated by an inciting event (e.g., surgery or trauma).
• History of clinically significant cardiovascular disease, or clinically significant abnormalities in rhythm or conduction during Screening ECG, including:
  • 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.
• 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.
• Any condition known to significantly interfere with absorption, distribution, metabolism, or excretion of oral drugs in the opinion of the Investigator.
• Moderate or severe hepatic impairment that meets criteria for Child-Pugh Class B or C (Appendix 6), or active viral hepatitis, including:
  • Active hepatitis B virus (HBV) infection: patients with positive hepatitis B surface antigen (HBsAg) are excluded. Patients with positive hepatitis B core antibody (anti-HBc) and negative HBsAg require hepatitis B polymerase chain reaction (PCR) evaluation before enrollment. Patients who are hepatitis B PCR positive will be excluded.
  • Active hepatitis C virus (HCV) infection: patients who are positive for HCV antibody are eligible if PCR is negative for HCV RNA. PCR testing is only required if HCV antibody testing is positive.
• Uncontrolled human immunodeficiency virus (HIV) off antiretrovirals, or on antiretrovirals with detectable viral load. Note: Patients with a known history of HIV must have viral load assessed for eligibility and must be on a stable antiretroviral regimen that can be administered concurrent with pacritinib.
• Positive Quantiferon (or other interferon gamma release assay) during Screening. Note: patients with indeterminant Quantiferon results may enroll.
• 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. 22. Any unstable disease, intercurrent illness, abnormality, or event (i.e., psychiatric episode, adverse social situation) that could compromise patient safety or affect the conduct of the study, in the judgment of the treating physician.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.
• Persons committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 1/09/2025. Questions regarding updates should be directed to the study team contact.