E1 Ubiqutin-activating Enzyme, X-linked, Autoinflammatory, Somatic SyndromePhase 1NCT06538181
Pacritinib in Vacuoles, E1 Ubiqutin-activating Enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) Syndrome
A Phase 1 study testing Pacritinib in people with E1 Ubiqutin-activating Enzyme, X-linked, Autoinflammatory, Somatic Syndrome and VEXAS, run by Washington University School of Medicine at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- E1 Ubiqutin-activating Enzyme, X-linked, Autoinflammatory, Somatic Syndrome, VEXAS, Vexas Syndrome
- What is being tested?
- Pacritinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Feb 2025to 28 Feb 2029
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- 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)
Show all 30Show fewer
- 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.
Who cannot join
- 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.
Show all 15Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
Meagan A Jacoby, M.D., Ph.D., 314-454-8306, mjacoby@wustl.edu
Meagan A Jacoby, M.D., Ph.D.
About this study
Official title: A Phase 1 Study of Pacritinib in Vacuoles, E1 Ubiqutin-activating Enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) Syndrome
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.
- Conditions
- E1 Ubiqutin-activating Enzyme, X-linked, Autoinflammatory, Somatic Syndrome, VEXAS, Vexas Syndrome
- Being tested
- Pacritinib
- Keywords
- VEXAS, Autoinflammatory, UBA1, Pacritinib
- Medical subject headings
- VEXAS syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PacritinibDrug
Starting dose is 200 mg twice per day by mouth. Dose level -1 is 100 mg twice per day by mouth.
| Study group | Role | What they receive |
|---|---|---|
| Dose De-Escalation (Safety Run-in): Pacritinib | Experimental | Assigned dose of pacritinib by mouth twice per day. Each cycle is 28 days and participants can receive up to 12 cycles of treatment. |
| Dose Expansion: Pacritinib | Experimental | Recommended phase II dose of pacritinib by mouth twice per day. Each cycle is 28 days and participants can receive up to 12 cycles of treatment. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with dose-limiting toxicities (DLTs)
Dose-limiting toxicities (DLTs) are adverse events defined by the protocol that occur during the DLT observation period (Cycle 1) of the study, unless clearly attributable to underlying disease or another cause unrelated to the study.
Measured: Through completion of cycle 1 (estimated to be 28 days)
Recommended phase II dose (RP2D)
The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity (DLT) during the first cycle. The recommended phase II dose (RP2D) will be less than or equal to the MTD. If the MTD is not reached, and in the opinion of the investigators, the toxicity profile is acceptable, Dose Level 1 will be the RP2D.
Measured: Through completion of cycle 1 (each cycle is 28 days) for all treated participants
Secondary outcomes (14)
Change in white blood cell count
Measured: Baseline, 1 month, 3 months, 6 months, and 12 months
Change in absolute neutrophil count
Measured: Baseline, 1 month, 3 months, 6 months, and 12 months
Change in absolute lymphocyte count
Measured: Baseline, 1 month, 3 months, 6 months, and 12 months
Change in hemoglobin
Measured: Baseline, 1 month, 3 months, 6 months, and 12 months
Change in platelets
Measured: Baseline, 1 month, 3 months, 6 months, and 12 months
Number of participants with hematologic improvement as measured with neutrophils
Using IWG 2018 criteria
Measured: Through completion of treatment (estimated to be 12 months)
Number of participants with hematologic improvement as measured with hemoglobin
Using IWG 2018 criteria
Measured: Through completion of treatment (estimated to be 12 months)
Number of participants with hematologic improvement as measured with platelets
Using IWG 2018 criteria
Measured: Through completion of treatment (estimated to be 12 months)
UBA1 variant allele frequency
Measured: Baseline, 1 month, 3 months, 6 months, and 12 months
Change in C reactive protein (CRP)
Measured: Baseline, 1 month, 3 months, 6 months, and 12 months
Change in ferritin
Measured: Baseline, 1 month, 3 months, 6 months, and 12 months
Change in ESR
Measured: Baseline, 1 month, 3 months, 6 months, and 12 months
Change in inflammatory and rheumatologic symptoms as measured by the VEXAS Disease Activity Index
Measured: Baseline, 1 month, 3 months, 6 months, and 12 months
Time to next treatment
Measured: Through completion of follow-up (estimated to be 24 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2024
- Study start13 Feb 2025
- Primary completion31 Mar 2027 (estimated)
- Study completion28 Feb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for E1 Ubiqutin-activating Enzyme, X-linked, Autoinflammatory, Somatic SyndromeStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Swedish Orphan Biovitrum
- Responsible party
- Sponsor
- Investigators
- Meagan A Jacoby, M.D., Ph.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06538181
- Sponsor's protocol ID
- 202412141
- Status last verified
- Jul 2026
- First submitted
- 31 Jul 2024
- Last updated
- 15 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie results after deidentification
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of Pacritinib in Vacuoles, E1 Ubiqutin-activating Enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) Syndrome
- ClinicalTrials.gov ID
- NCT06538181
- Acronym / sponsor ID
- 202412141
- Conditions
- E1 Ubiqutin-activating Enzyme, X-linked, Autoinflammatory, Somatic Syndrome, VEXAS, Vexas Syndrome
- Keywords
- VEXAS, Autoinflammatory, UBA1, Pacritinib
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- Swedish Orphan Biovitrum
- Study start
- 13 Feb 2025 (actual)
- Primary completion
- 31 Mar 2027 (estimated)
- Study completion
- 28 Feb 2029 (estimated)
- First posted
- 5 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dose De-Escalation (Safety Run-in): Pacritinib | Experimental | –Assigned dose of pacritinib by mouth twice per day. Each cycle is 28 days and participants can receive up to 12 cycles of treatment. |
| Dose Expansion: Pacritinib | Experimental | –Recommended phase II dose of pacritinib by mouth twice per day. Each cycle is 28 days and participants can receive up to 12 cycles of treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (30 listed)
- 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:
- 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.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PacritinibStarting dose is 200 mg twice per day by mouth. Dose level -1 is 100 mg twice per day by mouth. | Drug | – |
Primary outcome
Number of participants with dose-limiting toxicities (DLTs)
Time frame: Through completion of cycle 1 (estimated to be 28 days)
Dose-limiting toxicities (DLTs) are adverse events defined by the protocol that occur during the DLT observation period (Cycle 1) of the study, unless clearly attributable to underlying disease or another cause unrelated to the study.
Recommended phase II dose (RP2D)
Time frame: Through completion of cycle 1 (each cycle is 28 days) for all treated participants
The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity (DLT) during the first cycle. The recommended phase II dose (RP2D) will be less than or equal to the MTD. If the MTD is not reached, and in the opinion of the investigators, the toxicity profile is acceptable, Dose Level 1 will be the RP2D.
14 secondary outcomes
Change in white blood cell count
Time frame: Baseline, 1 month, 3 months, 6 months, and 12 months
Change in absolute neutrophil count
Time frame: Baseline, 1 month, 3 months, 6 months, and 12 months
Change in absolute lymphocyte count
Time frame: Baseline, 1 month, 3 months, 6 months, and 12 months
Change in hemoglobin
Time frame: Baseline, 1 month, 3 months, 6 months, and 12 months
Change in platelets
Time frame: Baseline, 1 month, 3 months, 6 months, and 12 months
Number of participants with hematologic improvement as measured with neutrophils
Time frame: Through completion of treatment (estimated to be 12 months)
Number of participants with hematologic improvement as measured with hemoglobin
Time frame: Through completion of treatment (estimated to be 12 months)
Number of participants with hematologic improvement as measured with platelets
Time frame: Through completion of treatment (estimated to be 12 months)
UBA1 variant allele frequency
Time frame: Baseline, 1 month, 3 months, 6 months, and 12 months
Change in C reactive protein (CRP)
Time frame: Baseline, 1 month, 3 months, 6 months, and 12 months
Change in ferritin
Time frame: Baseline, 1 month, 3 months, 6 months, and 12 months
Change in ESR
Time frame: Baseline, 1 month, 3 months, 6 months, and 12 months
Change in inflammatory and rheumatologic symptoms as measured by the VEXAS Disease Activity Index
Time frame: Baseline, 1 month, 3 months, 6 months, and 12 months
Time to next treatment
Time frame: Through completion of follow-up (estimated to be 24 months)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2026.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie results after deidentification
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Meagan A Jacoby, M.D., Ph.D. principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pacritinib in people with E1 Ubiqutin-activating Enzyme, X-linked, Autoinflammatory, Somatic Syndrome and VEXAS, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 30 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Meagan A Jacoby, M.D., Ph.D. (314-454-8306, mjacoby@wustl.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with dose-limiting toxicities (DLTs) (time frame: Through completion of cycle 1 (estimated to be 28 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2026.