Pacritinib for VEXAS Syndrome

Recruiting at 40 trial locations

Overseen By Study Physician

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Swedish Orphan Biovitrum

Must be taking: Glucocorticoids

Must not be taking: CYP3A4 inhibitors/inducers

Disqualifiers: Transplant, MDS, Malignancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

78 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you must be on a stable dose of certain medications like prednisone or prednisolone. Some medications, like strong CYP3A4 inhibitors or inducers, must be stopped before joining the trial.

What data supports the effectiveness of the drug Pacritinib for VEXAS Syndrome?

Pacritinib has shown effectiveness in reducing spleen size and improving symptoms in patients with myelofibrosis, a blood disorder, and has been studied for its potential in treating other blood-related conditions. It works by inhibiting specific proteins (JAK2 and FLT3) involved in these diseases, which might also be relevant for VEXAS Syndrome. ^{1 2 3 4 5}

How is the drug pacritinib unique for treating VEXAS Syndrome?

Pacritinib is unique because it is a selective inhibitor of specific enzymes (JAK2 and FLT3) involved in blood cell growth, which may help manage conditions like VEXAS Syndrome that lack standard treatments. It is taken orally and has shown promising results in treating other blood-related disorders with a good safety profile. ^{1 4 5 6 7}

What is the purpose of this trial?

This study 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. 78 patients will be enrolled, randomized to either pacritinib dose A, pacritinib dose B + placebo, or placebo. Randomization will be stratified by prescribed GC dose on the day of randomization.

Research Team

Study Physician

Principal Investigator

Sobi, Inc.

Eligibility Criteria

This trial is for patients with VEXAS syndrome, a rare inflammatory condition. Participants must meet specific health criteria to join, but the provided information doesn't detail these requirements. Those eligible will be randomly assigned to different treatment groups.

Inclusion Criteria

My tests show a specific genetic mutation in my blood or bone marrow.

I am currently on a stable dose of steroids for my condition.

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

Exclusion Criteria

I have HIV that is not well-controlled, with or without medication.

I am not on steroids for conditions other than VEXAS syndrome that would affect the study.

I've been in ICU more than once for VEXAS Syndrome flare-ups in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-blind Treatment

Participants receive either pacritinib dose A, pacritinib dose B plus placebo, or placebo for up to 24 weeks

24 weeks

Open-label Treatment

Participants receive pacritinib in an open-label setting for up to 48 weeks

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Pacritinib

Trial Overview The study tests pacritinib's effectiveness and safety in treating VEXAS syndrome. A total of 78 patients will receive either one of two doses of pacritinib or a placebo, with their group determined by chance and adjusted based on their current medication dosage.

Participant Groups

Group I: Pacritinib + placebo Experimental Treatment 2 Interventions

To receive oral administration of pacritinib dose B plus placebo for up to 24 weeks

Group II: Pacritinib Experimental Treatment 1 Intervention

To receive oral administration of pacritinib dose A for up to 24 weeks.

Group III: Placebo Placebo Group 1 Intervention

To receive oral administration of placebo for up to 24 weeks.

Who Is Running the Clinical Trial?

Swedish Orphan Biovitrum

Lead 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

PSI CRO

Industry Sponsor

Trials

13

Recruited

2,800+

Findings from Research

Pacritinib, particularly at a dose of 200 mg twice per day, showed significant efficacy in treating advanced myelofibrosis in patients who were intolerant or resistant to ruxolitinib, with a spleen volume response rate of 9.3%.

The study demonstrated an acceptable safety profile for pacritinib, with no increase in severe hemorrhagic or cardiac events at the highest dose, making it a promising option for patients with severe thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determining the recommended dose of pacritinib: results from the PAC203 dose-finding trial in advanced myelofibrosis. Gerds, AT., Savona, MR., Scott, BL., et al.[2021]

In a study involving 536 myelofibrosis patients, pacritinib demonstrated superior efficacy in reducing spleen size and improving symptoms compared to best available therapy, particularly in patients with low or absent JAK2V617F allele burden.

Pacritinib was effective across all JAK2V617F allele burden quartiles, showing significant spleen response rates in patients with low allele burden (0%-25% and 25%-50%), while no responses were observed in the best available therapy group for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pacritinib demonstrates spleen volume reduction in patients with myelofibrosis independent of JAK2V617F allele burden. Tremblay, D., Mesa, R., Scott, B., et al.[2022]

Pacritinib was found to be well tolerated in patients with myelofibrosis, with a maximum tolerated dose established at 500 mg once daily and a recommended phase 2 dose of 400 mg once daily, showing manageable side effects and a low incidence of severe myelosuppression.

In the phase 2 part of the study, 23.5% of patients achieved a significant reduction in spleen volume after 24 weeks, indicating clinical activity, while 38.9% reported improved quality of life, highlighting its potential as an effective treatment for myelofibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1/2 study of pacritinib, a next generation JAK2/FLT3 inhibitor, in myelofibrosis or other myeloid malignancies. Verstovsek, S., Odenike, O., Singer, JW., et al.[2022]

Pacritinib is a selective inhibitor of Janus kinase 2 and FMS-related tyrosine kinase 3, showing potential for treating blood cancers like myeloproliferative neoplasias and acute myeloid leukemia, with strong antiproliferative effects and the ability to induce cell death.

In early-phase clinical trials, pacritinib demonstrated promising efficacy and an acceptable safety profile, with mild to moderate gastrointestinal issues being the most common side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profile of pacritinib and its potential in the treatment of hematologic disorders. Hatzimichael, E., Tsolas, E., Briasoulis, E.[2022]

Pacritinib has shown promising efficacy in treating myelofibrosis (MF), with 31% of patients experiencing a significant reduction in spleen volume and 42% showing improvement in spleen size through physical examination after 24 weeks.

The treatment demonstrated a favorable safety profile, particularly for patients with preexisting anemia and thrombocytopenia, although common side effects included diarrhea and nausea, leading to treatment discontinuation in 26% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a phase 2 study of pacritinib (SB1518), a JAK2/JAK2(V617F) inhibitor, in patients with myelofibrosis. Komrokji, RS., Seymour, JF., Roberts, AW., et al.[2022]

Pacritinib is a potent inhibitor of JAK2 and FLT3 that shows clinical efficacy in treating myelofibrosis without causing myelosuppression, which is a common side effect of other JAK inhibitors.

The drug selectively inhibits JAK2 while sparing JAK1, and it also reduces harmful cytokines, suggesting potential therapeutic benefits in other blood cancers and inflammatory diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive kinase profile of pacritinib, a nonmyelosuppressive Janus kinase 2 inhibitor. Singer, JW., Al-Fayoumi, S., Ma, H., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Pacritinib (SB1518), a JAK2/FLT3 inhibitor for the treatment of acute myeloid leukemia. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Determining the recommended dose of pacritinib: results from the PAC203 dose-finding trial in advanced myelofibrosis. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Pacritinib demonstrates spleen volume reduction in patients with myelofibrosis independent of JAK2V617F allele burden. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Phase 1/2 study of pacritinib, a next generation JAK2/FLT3 inhibitor, in myelofibrosis or other myeloid malignancies. [2022]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Profile of pacritinib and its potential in the treatment of hematologic disorders. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Results of a phase 2 study of pacritinib (SB1518), a JAK2/JAK2(V617F) inhibitor, in patients with myelofibrosis. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Comprehensive kinase profile of pacritinib, a nonmyelosuppressive Janus kinase 2 inhibitor. [2022]