ClinicalTrials.gov record NCT06538181
Pacritinib in Vacuoles, E1 Ubiqutin-activating Enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) Syndrome
A Phase 1 Study of Pacritinib in Vacuoles, E1 Ubiqutin-activating Enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) Syndrome
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AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
This is an open-label, single-arm Phase 1 study testing pacritinib in people with VEXAS syndrome. The study starts with a safety run-in cohort at 200 mg twice daily, may reduce to 100 mg twice daily if needed, and then enrolls an expansion group for additional data. Treatment is given in 28-day cycles for up to 12 cycles, with total planned enrollment up to 15 participants. The main goals are to assess dose-limiting toxicities and identify a recommended dose for later studies.
What it is studying. The study is testing the safety and tolerability of oral pacritinib in people with VEXAS syndrome and aims to identify a recommended phase II dose. It also measures blood counts, UBA1 variant allele frequency, inflammatory markers, and disease activity over time.
What the researchers hope to learn. Determine how safe and tolerable pacritinib is in people with VEXAS syndrome; define dose-limiting toxicities and a recommended phase II dose; collect data on hematologic measures, UBA1 variant allele frequency, inflammatory markers, and disease activity to inform future studies.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
VEXAS (vacuoles, E1 ubiqutin-activating enzyme, X-linked, autoinflammatory, somatic syndrome) is a recently described disorder with severe hematologic and rheumatologic manifestations caused by somatic variants in the ubiquitin- activating enzyme gene, UBA1, that is acquired in hematopoietic progenitor cells. Patients are often debilitated by autoinflammatory symptoms and there is currently no standard of care available. There is a clinically unmet need for better therapies in VEXAS Syndrome. There have been no prospective clinical trials of JAK-I in VEXAS syndrome. The investigators hypothesize that pacritinib, as a JAK2/IRAK1 inhibitor with a manageable safety profile in myelofibrosis patients with thrombocytopenia, will improve the autoinflammatory and hematologic manifestations of VEXAS syndrome with a tolerable toxicity profile. The investigators propose a single arm, pilot Phase 1 study evaluating the safety and tolerability of pacritinib in patients with VEXAS syndrome with an initial safety run-in phase of 6 patients treated with pacritinib 200mg twice daily (BID) on days 1-28 of a continuous 28 day cycle. If no more than 1 patient experiences a dose-limiting toxicity (DLT), the investigators will enroll an expansion cohort to gain additional toxicity and efficacy data, for a total enrollment of 15 patients. If more than 1 patient experiences a DLT during the safety run-in phase, the investigators will decrease the dose to 100 mg BID, and if no more than 1 of 6 patients experiences a DLT, the investigators will complete the expansion cohort as above for up to a total enrollment of 15 patients. If more than 1 patient experiences a DLT at 100 mg BID, the investigators will discontinue the study. Patients will be treated for up to 12 cycles.
Interventions being studied
Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.
- Drug
- Pacritinib
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
Inclusion criteria
- Patients must have UBA1 mutation with a variant allele frequency (VAF) of ≥ 2% detected on a next generation sequencing panel and have at least one of the following current or past clinical manifestation of VEXAS syndrome, as determined by the attending physician:
- skin rash
- vasculitis
- chondritis
- ocular/orbital inflammation (e.g., uveitis/iritis, episcleritis)
- genitourinary inflammation (e.g., epididymitis/orchitis)
- arthritis/arthralgias
- pulmonary inflammation (e.g., alveolitis/pleural effusion,)
- fever
- thrombosis
- splenomegaly
- hepatomegaly
- myocarditis or pericarditis
- cytopenias (defined as hemoglobin <11 g/dL, platelets < 100 X 10\^9 /L, OR absolute neutrophil count <1.0 X 10\^9 /L).
- Patients with VEXAS syndrome who have never been treated with a JAK-I will be eligible to enroll on study. A stable corticosteroid dose must be maintained for at least 14 days prior to start of pacritinib.
- Patients who have previously been treated with a JAK-I other than pacritinib, or who are currently being treated with a JAK-I other than pacritinib, may be eligible after a 28 day washout if either (i) their symptoms are not adequately controlled, as determined by the treating physician, or (ii) they have been unable to taper corticosteroids to an equivalent of <10 mg prednisone/day, and in the opinion of the treating physician, may benefit from a change in JAK-I. A stable corticosteroid dose must be maintained for at least 14 days prior to start of pacritinib.
- At least 18 years of age.
- ECOG performance status ≤ 3.
- Organ function as defined below:
- Absolute neutrophil count ≥ 0.5 K/cumm
- Platelets ≥ 25 K/cumm
- PT/PTT <2.5 X upper limit of normal (ULN)
- Total bilirubin ≤ 1.5 x IULN
- AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
- Creatinine clearance ≥ 30 mL/min by Cockcroft-Gault
- QTcF < 480 msec.
- The effects of pacritinib on the developing human fetus are unknown. For this reason and because pacritinib was shown to be teratogenic in animal studies, women of childbearing potential and men must agree to use highly effective contraception prior to study entry, for the duration of study participation, and for 30 days after completion of study treatment. Hormonal contraception is no longer considered highly effective alone as pacritinib is a CYP3A4 inducer and accelerated progesterone metabolism. The contraceptive methods considered highly effective for WOCBP who receive pacritinib are intrauterine devices, bilateral tubal occlusion, vasectomized partner, or total sexual abstinence. Hormonal contraceptives (e.g., Depo-Provera) alone are not considered highly effective methods of contraception on their own when in treatment with pacritinib; such hormonal contraceptives must be combined with an additional barrier method (condom, diaphragm with spermicidal gel, or condoms with spermicides to be considered highly effective. Highly effective contraceptive methods in males include vasectomy, sexual abstinence, and condoms when combined with their partner using a highly effective method (including oral contraceptives).
- Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
- Ability to understand and willingness to sign an IRB approved written informed consent document or that of legally authorized representative, if applicable.
- Patients with myelodysplastic neoplasms (MDS) or plasma cell dyscrasias are eligible if they are not undergoing active treatment. Supportive care is permitted.
Exclusion criteria
- Prior use of pacritinib.
- Use of another JAK inhibitor within 28 days of C1D1 of pacritinib.
- Currently receiving any other investigational agents. Patients may be eligible after 28 day washout.
- Thrombotic events (arterial or venous) within 60 days prior to enrollment.
- Any recent clinically significant bleeding within at least 7 days prior to enrollment.
- Any active or acute infection.
- History of malignancy within the prior 2 years, with the exception of MDS and plasma cell dyscrasias, or non-melanoma skin cancers that have been treated.
- History of clinically significant cardiovascular disease or clinically significant abnormalities in rhythm or conduction during screening EKG, including severe cardiac events, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or heart failure.
- Currently receiving immunosuppressants (other than corticosteroids), disease-modifying antirheumatic drugs (DMARDs), or biologic cytokine inhibitors. Patients may be eligible after 28 day washout.
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to pacritinib.
- Concurrent use of strong CYP3A4 inhibitors or inducers. Patients may be eligible after washout period of 28 days (or 5 half-lives, whichever is shorter).
- Diagnosis or history of moderate (Child-Pugh B) and severe hepatic impairment (Child-Pugh C).
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test within 7 days of C1D1 or negative urine pregnancy test within 3 days of C1D1.
- Known active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV).
- Patients with latent tuberculosis. Patients must have a negative T-Spot during screening to be eligible.
Study description and what participation involves
The registry record has no detailed description beyond the summary above.
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
Participants take pacritinib by mouth twice daily (starting dose 200 mg BID; a lower dose of 100 mg BID may be used if needed). Treatment is given in 28-day cycles for up to 12 cycles, beginning with a safety run‑in group; dose adjustments or stopping can occur for side effects. Expect regular clinic visits with blood tests (blood counts and inflammatory markers), ECGs, and measurements including UBA1 VAF and disease activity assessments at baseline and at specified times (for example 1, 3, 6 and 12 months); pregnancy testing is required for women of childbearing potential. The study includes close safety monitoring during the first cycle (the DLT observation period) and ongoing follow-up for outcomes.
How the study is structured. Interventional, open-label Phase 1 study with a non-randomized, single-arm design. A safety run-in cohort of up to 6 patients receives pacritinib 200 mg twice daily (with a planned dose reduction to 100 mg twice daily if predefined toxicities occur), followed by an expansion cohort to collect more safety and activity data, up to about 15 participants total. Treatment is oral, given continuously in 28-day cycles for up to 12 cycles; there is no masking.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- This is an early-phase study, mainly about safety and dose. What is already known about this treatment?
- The listed sites are in United States. Is any of them reachable for me, and does the study help with travel?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on VEXAS syndrome
Important dates
- Study start
- Feb 13, 2025
- Primary completion
- Mar 31, 2027 (estimated)
- Study completion
- Feb 28, 2029 (estimated)
- Target enrollment
- 15 participants (estimated)
- Last updated on registry
- Jul 16, 2025
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- Washington University School of Medicine
- Collaborators
- Swedish Orphan Biovitrum
Central study contact
If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.
- Meagan A Jacoby, M.D., Ph.D. 📞 314-454-8306 ✉ mjacoby@wustl.edu
Participating sites (1)
- Washington University School of MedicineRecruiting
St Louis, Missouri, 63110 · United States
- Meagan A Jacoby, M.D., Ph.D. · 314-454-8306 · mjacoby@wustl.edu
- Meagan A Jacoby, M.D., Ph.D.
- Matthew J Walter, M.D.
- Colin Diffie, M.D.
- Christine Yokoyama, M.D., Ph.D.
- Chongliang (Jason) Luo, Ph.D.
Terms used on this page · explanations by MedicalUpdates.ai
- standard of care
- Treatment generally considered appropriate for a condition in a particular clinical setting. It can vary by patient, place and over time. In many studies the new treatment is added to, or compared with, standard of care.
- single arm
- All participants receive the same treatment or follow the same plan. There is no comparison group within the study.
- run-in
- A period at the start of a study, before the study treatment begins, used for example to confirm that participants meet the criteria or to record their usual symptoms.
- dose-limiting toxicity
- A side effect, defined in advance, that is severe enough to limit how far the dose can be raised in a dose-escalation study. How many such events stop escalation is set by the study's rules.
- cohort
- A group of people who share a characteristic, such as a diagnosis, and are studied together. 'Prospective' means they are followed forward from enrolment; 'retrospective' means existing records are reviewed.
- enrollment
- The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
- absolute neutrophil count
- The number of neutrophils, a type of white blood cell that fights infection, in a blood sample. Studies often require it to be above a set level.
- corticosteroid
- Steroid medicines, such as prednisone, that reduce inflammation. Studies often require a stable dose at entry or measure whether the study treatment allows the dose to be reduced.
- washout
- A period during which a participant stops a previous treatment before starting the study treatment, so the earlier treatment does not affect the results.
- ECOG performance status
- A scale from 0 to 5 that describes how a person's condition affects daily activity. 0 means fully active; 1 means restricted in strenuous activity; 2 means able to self-care but unable to work; higher numbers mean more limitation.
- upper limit of normal
- The highest value of a blood test that a laboratory considers normal. Criteria such as '≤ 3 × ULN' mean the result must be no more than three times that value.
- Creatinine clearance
- A measure of kidney function, calculated from a blood creatinine level together with age, weight and sex.
- QTcF
- A recording of the heart's electrical activity. QTc is one measurement from it; some drugs are avoided if it is prolonged.
- women of childbearing potential
- Studies often ask participants who could become pregnant, or could father a child, to use contraception during the study and for a period afterwards, because the effect of the treatment on a pregnancy is unknown.
- written informed consent
- The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
- legally authorized representative
- A person who is legally allowed to make decisions, including consent to research, on behalf of someone who cannot consent for themselves.
- investigational
- A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
- during screening
- The checks done before enrolment to see whether a person qualifies, such as tests, scans or a review of medical history.
- immunosuppressants
- A medicine that reduces the activity of the immune system. Studies of autoimmune conditions often require a stable dose, a prior failure, or a washout of such medicines.
- 5 half-lives
- The time it takes for the amount of a drug in the body to fall by half. 'Five half-lives' is often used as the point at which a previous drug has essentially left the body.
- Inclusion Criteria
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- Exclusion Criteria
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
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