Pacritinib for VEXAS Syndrome

Overseen By Meagan A Jacoby, M.D., Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Washington University School of Medicine

Must not be taking: Immunosuppressants, DMARDs, Biologics, others

Disqualifiers: Recent thrombotic events, Active infection, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

15 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires a 28-day washout period (time without taking certain medications) for those currently on another JAK inhibitor or investigational agents. If you're on immunosuppressants, DMARDs, biologic cytokine inhibitors, or strong CYP3A4 inhibitors/inducers, you may also need a 28-day washout. A stable corticosteroid dose must be maintained for at least 14 days before starting pacritinib.

What is the purpose of this trial?

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.

Research Team

Meagan Jacoby, M.D., Ph.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for patients with VEXAS syndrome, a severe autoinflammatory disorder without standard treatment options. Participants must have specific genetic changes in the UBA1 gene and suffer from related hematologic and rheumatologic issues.

Inclusion Criteria

I can understand and am willing to sign the consent form.

I have VEXAS syndrome and haven't used JAK inhibitors. I've been on a stable dose of corticosteroids for 2 weeks.

I've used a JAK inhibitor other than pacritinib, but it didn't control my symptoms or let me reduce steroids.

Exclusion Criteria

I have previously taken pacritinib.

I haven't taken any JAK inhibitor drugs in the last 28 days.

Currently receiving any other investigational agents. Patients may be eligible after 28 day washout.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-in

Initial safety run-in phase with 6 patients treated with pacritinib 200mg BID on days 1-28 of a continuous 28-day cycle

4 weeks

1 visit (in-person) per cycle

Expansion

Expansion cohort to gain additional toxicity and efficacy data, with treatment up to 12 cycles

12 months

1 visit (in-person) per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Pacritinib

Trial Overview The study tests pacritinib, a drug thought to help with VEXAS syndrome symptoms due to its action on certain enzymes. It's a Phase 1 trial starting with six people taking the drug daily for four weeks to check safety before possibly expanding to fifteen patients.

Participant Groups

Group I: Safety Run-in: Pacritinib Experimental Treatment 1 Intervention

Assigned dose of pacritinib by mouth twice per day. Each cycle is 28 days and participants can receive up to 12 cycles of treatment.

Group II: Expansion: Pacritinib Experimental Treatment 1 Intervention

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.

Pacritinib is already approved in United States for the following indications:

Approved in United States as Vonjo for:

• Intermediate or high-risk primary or secondary myelofibrosis with platelet counts below 50 × 10^9/L

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Swedish Orphan Biovitrum

Industry Sponsor

Trials

103

Recruited

13,300+

Dr. Guido Oelkers

Swedish Orphan Biovitrum

Chief Executive Officer since 2017

PhD in Economics

Dr. Lydia Abad-Franch

Swedish Orphan Biovitrum

Chief Medical Officer since 2023

MD, MBA