Randomized Study of SIR9900 for Safety and Effectiveness in Patients with VEXAS Syndrome

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What is this study about?

The study focuses on VEXAS Syndrome, a rare condition that causes inflammation, fever, anemia and problems with blood cells. The investigational medicine is an oral tablet called SIR9900, which will be tested at two different strengths and compared with a dummy pill, known as a placebo. All participants will take the tablets by mouth.

The purpose of the trial is to determine whether SIR9900 is safe and works better than the placebo, first by finding the best dose and then by seeing if it improves overall health in people with the disease. In the first part, participants are randomly assigned to receive either a low dose, a higher dose, or the placebo, and safety information such as side effects and lab test results is collected. In the second part, the dose that showed the most promise is given to a new group of participants, again compared with the placebo, to see if it leads to a better overall clinical response, meaning a noticeable improvement in symptoms.

During the study, participants will visit the clinic regularly for check‑ups, blood draws, and simple examinations, and they will be asked to report any new symptoms or problems. The study follows participants for several months, allowing researchers to watch for side effects, track changes in blood tests, and assess how well the medication controls the disease while participants continue any standard treatments they may be using.

1 baseline assessments

After joining the study, you will attend an initial visit where your medical history, current symptoms, and vital signs are recorded.

Blood samples will be taken to measure inflammation markers such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), ferritin, and other laboratory values.

An electrocardiogram (ECG) may be performed to check heart rhythm.

2 randomization and assignment

Based on the study design, you will be randomly assigned to receive either a 20 mg dose of SIR9900, a 30 mg dose of SIR9900, or a placebo tablet that looks the same.

The tablets are taken by mouth (oral route).

3 start of daily medication

You will begin taking one tablet each day as instructed by the study team.

The assigned dose (20 mg, 30 mg, or placebo) will be continued for the duration of the trial unless you experience a serious side effect or the study physician decides to stop the medication.

4 first safety check (week 1)

One week after starting the medication, you will return for a safety visit.

Blood will be drawn again to check for any early changes in laboratory values and to record any side effects that may have appeared.

5 mid‑study evaluation (week 12)

At twelve weeks, a follow‑up visit will be scheduled.

The same set of blood tests (CRP, ESR, ferritin, and other labs) will be repeated, and an ECG may be performed again.

Your overall health and any adverse events will be reviewed.

6 efficacy assessment (week 24)

The primary effectiveness measurement, called overall clinical response (OCR), will be evaluated at the end of week 24.

During this visit, the study team will also assess whether the dose of glucocorticoids (GC) you are taking has been successfully reduced to 10 mg per day or lower.

Blood tests and ECG will be repeated as part of the safety monitoring.

7 extended safety monitoring (week 48)

A safety visit at week 48 will include repeat laboratory testing and ECG to continue monitoring for any late‑appearing side effects.

8 final study visit (week 52)

The last scheduled visit occurs at week 52.

All remaining blood tests, ECG, and a final assessment of safety and any lasting benefits will be performed.

The study medication will be discontinued after this visit.

9 study completion

After the final visit, you will no longer be required to take study medication or attend scheduled visits.

Any further medical care will be managed by your regular healthcare provider.

Who Can Join the Study?

Must understand the study, agree to take part, and sign a written informed consent (a document showing you agree voluntarily).
Must be at least 18 years old when signing the consent form, and can be male or female.
Must have a confirmed genetic change (a pathogenic mutation) in the UBA1 gene at a specific spot (methionine‑41 or nearby). This must be shown by a lab test such as next‑generation sequencing, droplet digital PCR, or Sanger sequencing done on a blood or bone‑marrow sample.
Must have recent (within the past 6 months) signs that VEXAS is affecting at least one body system, such as skin problems, blood‑vessel inflammation, joint or cartilage inflammation, eye inflammation, swelling around the eyes, urinary‑tract inflammation, or lung inflammation.
Must be taking a steady dose of a steroid medicine (glucocorticoid, like prednisone or prednisolone) at 15‑45 mg per day for at least 10 days before joining the study. If you are on a lower steroid dose but have had a recent flare, you may be allowed after adjusting the dose.
Must have a Karnofsky Performance Status score of 50 % or higher, meaning you are able to care for yourself and carry out most daily activities.
Must have adequate organ function, which means:
- Liver enzymes (AST and ALT) not more than three times the normal upper limit;
- Total bilirubin not more than two times the normal limit (up to four times if you have Gilbert’s syndrome);
- Kidney function (creatinine clearance) at least 30 mL/min;
- White blood cell count (absolute neutrophil count) at least 500 per microliter;
- Blood clotting times (prothrombin time/INR and partial thromboplastin time/activated PTT) not more than 1.5 times the normal limit unless you are on blood thinners;
- Platelet count at least 25 × 10⁹ per liter;
- Less than 5 % immature blood cells (peripheral blasts) in the blood.
Must follow contraception rules: women who could become pregnant must use birth control, cannot be breastfeeding, and must have a negative pregnancy test. Women are considered able to become pregnant unless they are post‑menopausal (no periods for 12 months) or have had surgical sterilization.

Who Cannot Join the Study?

Prior allogenic hematopoietic stem cell transplant (allo‑HSCT) or solid organ transplant (except corneal) – a donor bone‑marrow transplant or organ transplant that makes participation unsafe.
Current use of systemic glucocorticoids (steroids) for other illnesses that might interfere with tapering the dose or measuring the study drug’s effect.
More than one stay in an intensive care unit (ICU) because of a VEXAS flare in the past 6 months.
Received nine or more units of red blood cell (RBC) transfusions in the 90 days before joining the study.
Has myelodysplastic syndrome (MDS) that needs cancer‑directed treatment, a bone‑marrow transplant, or is classified as high‑risk or very high‑risk by the Revised International Prognostic Scoring System (IPSS‑R). (Lower‑risk MDS may enroll.)
Had any malignancy (cancer) within the past year, except for cured non‑melanoma skin cancer or carcinoma in situ, and not including MDS as above. (Pre‑cancerous blood conditions like MGUS are allowed.)
Used hypomethylating agents (HMAs) – a type of cancer drug – within the last 6 months, or has taken more than four cycles of these drugs at any time.
Took non‑steroid anti‑inflammatory therapy or blood‑support treatments within the required wash‑out periods before enrollment.
Used anti‑platelet therapy (drugs that prevent clotting) other than low‑dose aspirin (≤100 mg daily) within the last 28 days.
Has multiple myeloma or high levels of abnormal proteins: serum M‑protein ≥3 g/dL, involved‑to‑uninvolved free light‑chain ratio ≥100, or involved free light‑chain level ≥100 mg/dL. (People with MGUS may enroll.)
Is taking prescription medicines that are strong inhibitors or inducers of liver enzymes CYP1A2, CYP3A, or CYP2C8 or have a narrow therapeutic window, within five drug half‑lives before the first dose; these drugs are also not allowed during the study.
Has a recent significant bleeding event, defined as a CTCAE grade ≥2 (moderate or worse) within the past 3 months, unless caused by a clear incident.
Has a history of serious heart disease or abnormal heart rhythm on a screening electrocardiogram (ECG), including a severe cardiac event (CTCAE grade ≥3) within the past 3 months or heart failure that limits normal activity.
Had a blood clot or embolism – such as deep vein thrombosis, pulmonary embolism, stroke, or transient ischemic attack – within the past 60 days.
Has moderate or severe liver disease classified as Child‑Pugh Class B or C, or active viral hepatitis.
Has uncontrolled human immunodeficiency virus (HIV) infection (not on treatment or with detectable virus despite treatment).
Tests positive for tuberculosis infection on a QuantiFERON or other interferon‑gamma release assay during screening.
Is currently enrolled in another interventional clinical study or has used an experimental therapy within the past 28 days or five drug half‑lives, whichever is longer.
Has an acute, active infection that requires systemic antimicrobial (antibiotic) treatment at the time of enrollment (except for preventive or chronic non‑acute use).
Is known to be allergic (hypersensitive) to SIR9900 or any of its inactive ingredients.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
IRCCS Humanitas Research Hospital	Rozzano	Italy
Policlinico “Tor Vergata”, Università degli Studi di Roma TOR VERGATA	Rome	Italy
Azienda Ospedaliera Universitaria Federico II Di Napoli	Naples	Italy

Other Sites

Site Name	City	Country
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico	Milan	Italy
Ospedale San Raffaele S.r.l.	Milan	Italy
Fondazione IRCCS Policlinico San Matteo	Pavia	Italy
Universita’ Politecnica Delle Marche	Ancona	Italy
Azienda Ospedaliera Ordine Mauriziano Di Torino	Turin	Italy
Azienda Ospedaliera Universitaria Di Cagliari	Monserrato	Italy

Trial status

Country	Status	Recruitment Start
Italy	Not yet recruiting	15.04.2026

Trial locations

SIR9900 is an experimental oral tablet being tested to see if it can help people with VEXAS syndrome, a rare inflammatory disease. In the study participants take the tablet by mouth, and researchers are looking at how safe it is, how well patients can tolerate it, and whether it improves the signs and symptoms of the condition compared with no active treatment. The trial aims to find the dose that provides the best benefit while keeping side effects low.

Investigated Diseases:

VEXAS syndrome

VEXAS syndrome – VEXAS syndrome is a rare inflammatory condition that begins in adulthood and mainly affects the blood and bone marrow. It causes episodes of fever, skin rashes, and joint pain that can come and go. Over time, blood counts may become low, leading to anemia or reduced platelets. The disease often requires ongoing steroid use, and patients may find it harder to lower the dose. Some people experience repeated flare‑ups that can affect daily activities. The condition can evolve slowly, with symptoms changing in intensity over months to years.

Trial ID:

2025-524918-28-00

Protocol code:

SIR9900-GLB-202

Trial Phase:

Therapeutic exploratory (Phase II)

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Randomized Study of SIR9900 for Safety and Effectiveness in Patients with VEXAS Syndrome

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?