Clinical trial • Phase II • Haematology
AZACITIDINE for VEXAS syndrome
Phase II trial of AZACITIDINE for VEXAS syndrome. open-label, none/not specified-controlled. 60 participants.
Overview
- Trial Therapeutic Area
- Haematology
- Trial Disease
- VEXAS syndrome
- Trial Stage
- Phase II
- Drug Modality
- Small molecule
Key dates
- Initial CTIS Submission Date
- 13-02-2024
- First CTIS Authorization Date
- 07-05-2024
Trial design
open-label, none/not specified-controlled Phase II trial across 12 sites in Denmark, Sweden, Norway and others.
- Open Label
- Yes
- Comparator
- None/Not specified
- Target Sample Size
- 60
Eligibility
Recruits 60 Participants must be at least 18 years old and possess the cognitive capacity to provide informed consent. No vulnerable population selected (isVulnerablePopulationSelected = false)..
- Pregnancy Exclusion
- Patients who have a condition where Azacitidine is contraindicated, including hypersensitivity to Azacitidine, advanced malignant hepatic tumors, pregnancy, and breastfeeding individuals.
- Vulnerable Population
- Participants must be at least 18 years old and possess the cognitive capacity to provide informed consent. No vulnerable population selected (isVulnerablePopulationSelected = false).
Inclusion criteria
- {"criterion_text":"- Participants must possess one of the currently described UBA1 mutations with a VAF > 10%. The currently described UBA1 mutations are: p.Met41Leu (c.121A.C), p.Met41Val (c.121A.G), p.Met41Thr (c.122T.C), p.Ser56Phe (c.167C>T), p.(splice)(c.118-1G>C) or intronic deletions like (c.118-9_118-2del) affecting the splice site\n- Participants must meet one of the following conditions: (1) Present with any degree of cytopenia, or (2) Exhibit inflammatory symptoms of VEXAS with/without cytopenia.\n- Participants must be at least 18 years old and possess the cognitive capacity to provide informed consent.\n- It is mandatory that male participants, who engage in sex with pre-menopausal (i.e. fertile) women, are willing to use barrier contraceptives (i.e condoms), during treatment with Azacitidine, and until three months after the last treatment. Additionally, it is highly recommended that their fertile partner also uses highly effective contraceptives during and for three months after the participants last treatment. Fertile female participants must exhibit a negative result on a pregnancy test before inclusion, demonstrate a commitment to monthly pregnancy testing and employment of safe contraceptive measures during treatment with Azacitidine, and until three months after the last treatment."}
Exclusion criteria
- {"criterion_text":"- Patients having received Prior therapy with hypomethylating agents (i.e., Azacitidine, Decitabine).\n- Patients having received or is planned to receive alloHSCT.\n- Patients with active cancer requiring treatment are excluded from participation in this study. Active cancer is defined as a diagnosis of cancer for which the patient is currently receiving treatment, such as chemotherapy, radiation therapy, immunotherapy, targeted therapy, or any other curative or disease-controlling intervention.\n- Concomitant treatment with Disease modifying antirheumatic drugs (DMARDs), Chemotherapy/Cytostatic agents, Immunosuppressives, Radiotherapy any novel biological response modifying agents, is not allowed in the trials regardless of the underlying condition for which they are used. These treatments must be discontinued at least 14 days prior to inclusion.\n- Failure to obtain bone marrow examination maximum 8 weeks prior to initiating Azacitidine treatment.\n- Patients who are diagnosed with severe comorbidities including decompensated cirrhosis, end-stage kidney disease requiring dialysis, Severe cardiac disease (LVEF <30%), Severe pulmonary disease (FEV1 < 50% of predicted or DLCO < 40%), or a severe immunodeficiency including a diagnosis of HIV. If any of these conditions are suspected but undiagnosed, relevant tests will be ordered prior to screening based on clinical suspicion. However, diagnostic tests for all potential severe comorbidities will not be conducted systematically for every candidate; clinical suspicion will guide the decision to investigate further.\n- Patients with Eastern Cooperative Oncology Group (ECOG) Performance Status > 2\n- Patients who have a condition where Azacitidine is contraindicated, including hypersensitivity to Azacitidine, advanced malignant hepatic tumors, pregnancy, and breastfeeding individuals."}
Endpoints
Primary endpoints
- {"endpoint_text":"- Primary endpoint: to assess the number and percentage of patients who experience a 50% relative reduction in VAF after completing six cycles of Azacitidine treatment.","definition_or_measurement_approach":"Assess number and percentage of patients achieving a 50% relative reduction in UBA1 Variant Allele Frequency (VAF) measured by comparing baseline VAF to VAF after completion of six cycles of Azacitidine."}
Recruitment
- Planned Sample Size
- 60
- Recruitment Window Months
- 114
- Consent Approach
- Participants (age ≥18) must have cognitive capacity to provide informed consent and must provide written informed consent. Country-specific subject information and informed consent form documents are included (examples: 'L1_SIS_and_ICF_description', 'L1_SIS_and_ICF_VEX-AZA_finland', 'D4_ Patient facing documents EORTC QLQ-C30 Norwegian', 'QLQ-C30 Danish'), indicating availability of country/language specific ICFs. No assent procedures for minors (study restricted to ≥18).
Geography
- Total Number Of Sites
- 12
- Total Number Of Participants
- 60
Denmark
- Earliest CTIS Part Ii Submission Date
- 16-04-2024
- Latest Decision Or Authorization Date
- 14-02-2025
- Processing Time Days
- 304
- Number Of Sites
- 3
- Number Of Participants
- 30
Sites
- Site Name
- Rigshospitalet
- Department Name
- Department of Hematology
- Principal Investigator Name
- Jakob Werner Hansen
- Principal Investigator Email
- Jakob.werner.hansen.01@regionh.dk
- Contact Person Name
- Jakob Werner Hansen
- Contact Person Email
- Jakob.werner.hansen.01@regionh.dk
- Site Name
- Aarhus Universitetshospital
- Department Name
- Dept. of Hematology
- Principal Investigator Name
- Marie Bill
- Principal Investigator Email
- maitof@rm.dk
- Contact Person Name
- Marie Bill
- Contact Person Email
- maitof@rm.dk
- Site Name
- Aalborg University Hospital
- Department Name
- Department of Hematology
- Principal Investigator Name
- Marianne Tang Severinsen
- Principal Investigator Email
- m.severinsen@rn.dk
- Contact Person Name
- Marianne Tang Severinsen
- Contact Person Email
- m.severinsen@rn.dk
Sweden
- Earliest CTIS Part Ii Submission Date
- 18-05-2025
- Latest Decision Or Authorization Date
- 05-06-2025
- Processing Time Days
- 18
- Number Of Sites
- 5
- Number Of Participants
- 10
Sites
- Site Name
- Uppsala University Hospital
- Department Name
- Department of Hematology
- Principal Investigator Name
- Daniel Moreno Berggren
- Principal Investigator Email
- Daniel.moreno_berggren@medsci.uu.se
- Contact Person Name
- Daniel Moreno Berggren
- Contact Person Email
- Daniel.moreno_berggren@medsci.uu.se
- Site Name
- Sahlgrenska University Hospital-Vaestra Goetalandsregionen
- Department Name
- Department of Hematology
- Principal Investigator Name
- Lena Von Bahr
- Principal Investigator Email
- lena.von.bahr@vgregion.se
- Contact Person Name
- Lena Von Bahr
- Contact Person Email
- lena.von.bahr@vgregion.se
- Site Name
- Region Oestergoetland (Universitetssjukhuset I)
- Department Name
- Department of Hematology
- Principal Investigator Name
- Johanna Ungerstedt
- Principal Investigator Email
- region@regionostergotland.se
- Contact Person Name
- Johanna Ungerstedt
- Contact Person Email
- region@regionostergotland.se
- Site Name
- Lund University Hospital
- Department Name
- Department of Hematology
- Principal Investigator Name
- Lars Nilsson
- Principal Investigator Email
- Lars.Nilsson@skane.se
- Contact Person Name
- Lars Nilsson
- Contact Person Email
- Lars.Nilsson@skane.se
- Site Name
- Karolinska University Hospital
- Department Name
- Department of Hematology
- Principal Investigator Name
- Maria Creignou
- Principal Investigator Email
- kta.karolinska@regionstockholm.se
- Contact Person Name
- Maria Creignou
- Contact Person Email
- kta.karolinska@regionstockholm.se
Norway
- Earliest CTIS Part Ii Submission Date
- 05-03-2026
- Latest Decision Or Authorization Date
- 23-03-2026
- Processing Time Days
- 18
- Number Of Sites
- 2
- Number Of Participants
- 10
Sites
- Site Name
- Haukeland University Hospital
- Department Name
- Department of hematology
- Principal Investigator Name
- Håkon Reikvam
- Principal Investigator Email
- hakon.reikvam@helse-bergen.no
- Contact Person Name
- Håkon Reikvam
- Contact Person Email
- hakon.reikvam@helse-bergen.no
- Site Name
- Oslo Universitetssykehus HF
- Department Name
- Department of hematoloy
- Principal Investigator Name
- Synne Thorkildsen
- Principal Investigator Email
- xasyto@ous-hf.no
- Contact Person Name
- Synne Thorkildsen
- Contact Person Email
- xasyto@ous-hf.no
Finland
- Earliest CTIS Part Ii Submission Date
- 29-04-2025
- Latest Decision Or Authorization Date
- 01-04-2026
- Processing Time Days
- 337
- Number Of Sites
- 2
- Number Of Participants
- 10
Sites
- Site Name
- Turku University Hospital
- Department Name
- Department of Hematology
- Principal Investigator Name
- Maija Valta Pauliina
- Principal Investigator Email
- maija.valta@tyks.fi
- Contact Person Name
- Maija Valta Pauliina
- Contact Person Email
- maija.valta@tyks.fi
- Site Name
- HUS-Yhtymae (Helsinki)
- Department Name
- Department of Hematology
- Principal Investigator Name
- Mikko Myllymäki
- Principal Investigator Email
- mikko.myllymaki@helsinki.fi
- Contact Person Name
- Mikko Myllymäki
- Contact Person Email
- mikko.myllymaki@helsinki.fi
Sponsor
Primary sponsor
- Full Name
- Rigshospitalet
- Organisation Type
- Hospital/Clinic/Other health care facility
- Country Of Registered Address
- Denmark
Third parties
- {"country":"Denmark","full_name":"Odense University Hospital","duties_or_roles":"code:1","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"Denmark","full_name":"Frederiksberg Hospital","duties_or_roles":"code:1","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"Denmark","full_name":"Aarhus Universitet","duties_or_roles":"code:1","organisation_type":"Educational Institution"}
Investigational products
- Investigational Product Name
- AZACITIDINE
- Active Substance
- AZACITIDINE
- Modality
- Small molecule
- Routes Of Administration
- SUBCUTANEOUS INJECTION
- Route
- SUBCUTANEOUS INJECTION
- Authorisation Status
- Authorised (SmPC provided)
- Maximum Dose
- 200 mg (max daily dose amount 200 mg)
Related trials
Other published trials that may interest you.
- Pacritinib for VEXAS syndrome
- (S)-4,5-DIHYDRO-2-[2-HYDROXY-4-(3,6-DIOXAHEPTYLOXY)PHENYL]-4-METHYL-4-THIAZOLECARBOXYLIC ACID for Transfusion-dependent alpha thalassemia | Transfusion-dependent beta thalassemia | Low-risk myelodysplastic syndromes
- Luspatercept for Myelofibrosis | Anemia associated with myeloproliferative neoplasm-associated myelofibrosis
- GIVINOSTAT for Chronic myeloproliferative neoplasm
- GOLCADOMIDE for Follicular lymphoma (advanced stage)