Ongoing Clinical Trials for VEXAS Syndrome
VEXAS syndrome is a rare genetic disorder that causes inflammation throughout the body and affects blood cell production. Currently, there are 3 ongoing clinical trials testing different medications for patients with this condition. These studies are taking place across several European countries and are investigating treatments that may help reduce symptoms and improve quality of life for patients who have not responded well to standard steroid therapy.
Clinical trial locations
- Denmark
- Finland
- France
- Germany
- Italy
- Spain
- Sweden
Study of Azacitidine Treatment in Patients with VEXAS Syndrome
This Phase II clinical trial is testing azacitidine, a medication typically used to treat blood disorders, in patients with VEXAS syndrome. The study aims to determine whether this treatment can reduce the amount of abnormal genetic material present in the body.
Who can participate: This trial is open to adults aged 18 years and older who have a confirmed genetic mutation in the UBA1 gene with a variant frequency greater than 10%. Participants must have either low blood cell counts of any severity, or inflammatory symptoms related to VEXAS syndrome. Both male and female participants must agree to use effective contraception during treatment and for three months afterward. Women who can become pregnant must have negative pregnancy tests before starting and agree to monthly testing throughout the study.
Who cannot participate: The trial excludes anyone under 18 years old, pregnant or breastfeeding women, and people with a history of severe allergic reactions to azacitidine. Other exclusion criteria include active uncontrolled infections, severe liver problems, severe kidney problems with creatinine clearance below 30 mL/min, active cancer other than VEXAS, recent major surgery within four weeks, unstable heart disease or recent heart attack within the last six months, life expectancy less than three months, bone marrow failure, or history of organ transplantation.
Treatment approach: Participants will receive azacitidine through injections under the skin for six treatment cycles, lasting up to 10 months. The medication will be given at doses up to 200 milligrams per day, with a maximum total dose of 10,000 milligrams over the treatment period. Throughout the study, doctors will monitor blood values to track changes in the UBA1 mutation levels, with the main goal being a 50% reduction in these abnormal genetic markers after completing all six cycles.
Investigational drug: Azacitidine is a medication that helps bone marrow produce normal blood cells and works by modifying how genes function in the body. It belongs to a class of drugs known as DNA methyltransferase inhibitors, which interfere with DNA production to help correct blood cell production in the bone marrow.
Study of pacritinib effectiveness and safety compared to placebo in patients with VEXAS syndrome
This clinical trial is examining whether pacritinib can effectively treat VEXAS syndrome, particularly in patients who require ongoing steroid treatment. The study will compare two different doses of pacritinib against a placebo to determine the best treatment approach.
Who can participate: The trial is open to adults aged 18 and older with confirmed genetic mutation in the UBA1 gene. Participants must have current or recent inflammation affecting at least one area of the body, such as skin, blood vessels, joints, eyes, reproductive organs, or lungs. They must be currently taking prednisone or prednisolone at a stable dose of 15-45 mg per day for at least 10 days, following at least four consecutive weeks of steroid treatment. Participants must have a Karnofsky Performance Status of 50% or higher, meaning they can care for themselves, and must have adequate organ function as shown through blood tests. Both men and women must agree to use effective birth control during the study and for 30 days afterward.
Who cannot participate: Exclusion criteria include prior treatment with pacritinib, active severe infections requiring treatment, history of severe allergic reactions to similar medications, significant heart problems or uncontrolled high blood pressure, severe liver or kidney problems, active cancer requiring treatment, pregnancy or breastfeeding, participation in other clinical trials within the past 30 days, mental health conditions that could interfere with study procedures, use of medications that could interact with the study drug, blood disorders that could affect results, planned major surgery during the study period, or any condition that the study doctor believes would make participation unsafe.
Treatment approach: The study consists of two phases lasting up to 52 weeks total. During the first phase, participants will not know whether they are receiving pacritinib or placebo. They will continue taking their current dose of prednisone or prednisolone, which will be adjusted according to a fixed schedule. Participants will need to maintain a daily diary recording medication use and complete quality of life questionnaires. In the second phase, all participants will receive pacritinib. Throughout the study, regular monitoring will include blood tests, heart rhythm checks through ECG tests, and assessment of symptoms and side effects.
Investigational drug: Pacritinib is an oral medication that works by targeting specific proteins in cells involved in inflammation. It blocks specific enzymes called JAK2 and IRAK1, which play roles in cellular signaling and inflammatory processes. The medication is taken as oral capsules and is being tested to determine the most effective dose for reducing symptoms associated with VEXAS syndrome.
Study of momelotinib in patients with VEXAS syndrome and myelodysplastic syndrome who are dependent on or do not respond to steroid treatment
This clinical trial is investigating momelotinib in patients with VEXAS syndrome who may also have myelodysplastic syndrome, a blood disorder affecting bone marrow function. The study focuses on patients who have not responded well to steroid treatment or who remain dependent on steroids.
Who can participate: Adults aged 18 and older with VEXAS syndrome confirmed by a UBA1 mutation test are eligible. Participants must have symptoms requiring treatment with immunosuppressive medications and at least 10 mg per day of steroid medications, with symptoms that are not well controlled by previous treatments. They must have a performance status of 0-2, meaning they can perform daily activities and are up and about more than 50% of waking hours. Adequate liver and kidney function is required, with kidney filtration rate above 30 ml/min. Participants can be taking only steroid medication at the time of joining but must stop other immune system medications 28 days before starting the study. Women who can become pregnant must have a negative pregnancy test within 24 hours before starting treatment and use effective birth control from four weeks before treatment until 12 weeks after. Men must use condoms during sexual activity with women who can become pregnant during treatment and for 12 weeks after.
Who cannot participate: The trial excludes anyone under 18 years old, those with active uncontrolled systemic infections, history of cancer within the past five years except successfully treated skin cancer, severe heart conditions including uncontrolled high blood pressure or recent heart attack, severe liver or kidney disease, pregnant or breastfeeding women, those currently participating in other clinical trials, people unable to provide informed consent, those with known allergic reactions to similar medications, significant mental health conditions that could interfere with study participation, or use of prohibited medications that could interact with the study drug.
Treatment approach: The study consists of two parts lasting up to 48 weeks. During the first four weeks, doctors will closely monitor how well participants tolerate the medication to determine the appropriate dose, with an additional four-week observation period if needed. Treatment response will be evaluated at weeks 4, 12, and 24, with regular blood tests to monitor the condition. Steroid medication doses may be adjusted during this period. A comprehensive final assessment will be conducted at 12 months to evaluate overall response to treatment, including blood tests, symptom evaluation, and assessment of steroid use reduction.
Investigational drug: Momelotinib is an oral medication taken in tablet form that works by blocking specific enzymes called Janus kinases (JAK1/JAK2). These enzymes are involved in inflammation and blood cell production pathways in the body. The medication is being tested to help reduce symptoms in patients who have not responded well to steroid treatments and may help manage both inflammatory symptoms and blood cell production issues.
Summary
There are currently three active clinical trials for VEXAS syndrome taking place across Europe. These trials are testing three different medications: azacitidine, pacritinib, and momelotinib. All three studies focus on patients who have confirmed genetic mutations in the UBA1 gene and are experiencing inflammatory symptoms or blood cell production problems.
The trials are distributed across seven European countries, with France participating in two studies, while Denmark, Finland, Sweden, Germany, Spain, and Italy are each hosting one trial. All three medications being tested work through different mechanisms: azacitidine modifies gene function, while pacritinib and momelotinib both block specific inflammatory proteins, though they target different pathways.
A common theme across these trials is the focus on patients who have not responded adequately to standard steroid treatment or who remain dependent on steroids. Two of the three trials specifically require participants to be currently taking steroid medications at stable doses. All studies include comprehensive monitoring protocols with regular blood tests and symptom assessments, and all require participants to use effective contraception during treatment due to potential risks to pregnancy.
These trials represent important research efforts to find more effective treatments for VEXAS syndrome, a condition that currently has limited therapeutic options beyond steroids and other immunosuppressive medications.
