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Trial registered on ANZCTR


Registration number
ACTRN12625000619448
Ethics application status
Approved
Date submitted
8/05/2025
Date registered
13/06/2025
Date last updated
13/06/2025
Date data sharing statement initially provided
13/06/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy of assigning treatment for participants with VEXAS syndrome with lenzilumab plus azacitidine
Scientific title
Targeted Immunotherapy for VEXAS syndrome: A Phase II Trial Exploring the Efficacy of Lenzilumab in Combination with Azacitidine
Secondary ID [1] 314153 0
VEXAS1
Universal Trial Number (UTN)
U1111-1321-3031
Trial acronym
LENAVEX (LENzilumab + Azacitidine for improving outcomes in VEXAS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
V - vacuoles are often seen in cells identified in bone marrow biopsies from patients with VEXAS syndrome. E - E1 ubiquitin activating enzyme, encoded by the UBA1 gene which is mutated in patients X - the UBA1 gene is located on the X chromosome. A - patients have autoinflammation. S - the mutations are somatic, meaning they are acquired at some point in life and not inherited. (VEXAS) 336986 0
Condition category
Condition code
Inflammatory and Immune System 333447 333447 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
VEXAS is an adult-onset autoinflammatory disease, caused by a genetic mutation (UBA1). The name is an acronym for features of the disease: Vacuoles in bone marrow cells, E1 ubiquitin conjugating enzyme

This prospective study will assess whether treatment responses for participants with VEXAS can be improved by targeting certain mutation sub-groups based on individual molecular profiling.

Lenzilumab 552 mg will be administered intravenously on days 1 & 15 of Cycle 1 and Day 1 only for the remaining 5 cycles.

Azacitidine will be administered subcutaneously at 75 mg/m2. Doses will be administered daily on 7 days out of the first 9 days of each cycle. Azacitidine will be administered for a total of 6 cycles.
Intervention code [1] 330748 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 341379 0
To evaluate the safety and tolerability of Lenzilumab (GM-CSF antibody) and azacitidine in patients with VEXAS as a composite primary outcome.
Timepoint [1] 341379 0
Baseline, after 3 months of treatment and end of study (6 months after commencement of treatment).
Secondary outcome [1] 447357 0
To evaluate the response rate in patients with VEXAS syndrome.
Timepoint [1] 447357 0
At baseline, after 3 months of treatment, at end of study (6 months after commencement of treatment).
Secondary outcome [2] 447779 0
To evaluate the durability of the response rate in patients with VEXAS syndrome.
Timepoint [2] 447779 0
At baseline, after 3 months of treatment, at end of study (6 months after commencement of treatment).

Eligibility
Key inclusion criteria
Inclusion criteria
1. Confirmed diagnosis VEXAS with documented evidence of mutation in UBA1
2. Aged 18 or older.
3. Documented evidence of current or past involvement of at least one of the following organ systems in VEXAS syndrome:
(a) cutaneous ( skin rash eg. neutrophilic dermatosis, cutaneous vasculitis, periorbital inflammation);
(b) vasculature (e.g., vasculitis);
(c) musculoskeletal (e.g., arthralgia, arthritis, articular chondritis);
(d) ocular (e.g., uveitis);
(e) genitourinary (e.g., epididymitis);
(f) pulmonary (e.g., pulmonary infiltrates, alveolitis), or
(g) fever.
(h) other Patients with sensorineural hearing loss, pleural effusion, thrombosis, splenomegaly, hepatomegaly, myocarditis, weight loss.
Other inflammatory signs may be considered for enrolment at the discretion of the trial management committee.
4. Chronic glucocorticoid therapies (More than or equal to 3 consecutive months leading up to enrolment) for treatment of VEXAS syndrome
OR
5. Documented prednisolone threshold dose >10 mg daily (highest prednisolone monotherapy dose at which CRP >25 mg/L (except patients on tocilizumab, anti-IL6 therapy) or at which new or worsening objectives clinical manifestations of VEXAS syndrome emerge)
6. Baseline prednisolone dose 15-60 mg/day and that has been stable for >10 days prior to enrolment
7. Willing and able to switch to prednisone from other glucocorticoids for the duration of the study.
8. ECOG greater than or equal to 2
9. Must have the following local laboratory results:
i. Liver function (total bilirubin greater than or equal to 4 x upper limit of normal [ULN], aspartate aminotransferase [AST] greater than or equal to 3 x ULN).:
ii. Kidney function: creatinine clearance >30 mL/min using Cockcroft-Gault formula. Note: the Adjusted Body Weight formula should be used for participants with a BMI of > 30. Actual Body weight should be used when BMI is < 30.
10. Ability to understand the requirements of the study and informed consent.
11. Reproductive status
(a)Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 8 days prior to the start of study drug.
(b)Women must not be breastfeeding.
(c) WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug, until 90 days post-treatment completion.
(d) Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug until 90 days post-treatment completion (duration of sperm turnover).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:
1. Major surgery within 2 weeks or having not recovered from surgery.
2. Treatment with G-CSF within 7 days of screening.
3. Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
4. Other concurrent uncontrolled medical conditions. These include, but are not limited to:, uncontrolled infections, acute or chronic liver and renal disease (not considered disease related), uncontrolled cardiovascular conditions, including ongoing cardiac arrhythmias (e.g., ventricular arrhythmias, Torsades de Pointes, or third-degree heart block without pacemaker insertion) or uncontrolled congestive cardiac failure.
5. Myocardial infarction or clinically significant pericardial effusion within the past month.
6. Stroke or transient ischemic attack within 3 months prior to treatment.
7. Active malignancy with and expected survival <3 months prior to enrolment.
8. Acute or chronic liver disease (including chronic hepatitis B and C infections). Hepatitis B Virus core antibody positivity is not an automatic exclusion and should be discussed with Trial Management Committee.
9. Patients with known active Hepatitis A infection. Testing for Hepatitis A is not required as part of screening for this study.
10. Participants with known human immunodeficiency viruses (HIV). Screening for HIV is not required for this study.
11. Participants who are unable to comply with requirements for contraception as per study requirements.
12. Current participation in another therapeutic clinical trial (participation in clinical trials that do not involve active interventions is not an exclusion for the study).
13. Prior treatment with an investigational agent within 28 days before Cycle 1 Day 1 (or within 5 half-lives of the investigational agent, whichever is longer). Participants must have recovered from any toxic effects of that therapy to greater than or equal to grade 1 or baseline grade.
14. Known presence of antibodies against Lenzilumab
15. Previous or pre-existing diagnosis of pulmonary alveolar proteinosis.
16. Hypoxaemia at screening (oxygen saturation on room air <94%).
17. Known active tuberculosis (TB), history of incompletely treated TB or suspected or known extrapulmonary TB. Screening for TB is not required for this study.
18. Prior allogeneic haematopoietic stem cell transplant (allo-HSCT) or solid organ transplant (other than corneal)

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/08/2025
Actual
Date of last participant enrolment
Anticipated
1/08/2026
Actual
Date of last data collection
Anticipated
1/06/2028
Actual
Sample size
Target
10
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 27915 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 44109 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 318664 0
Government body
Name [1] 318664 0
Australian Department of Health and Aged Care, Medical Research Future Fund (MRFF)
Country [1] 318664 0
Australia
Primary sponsor type
Other
Name
South Australian Health & Medical Research Institute Ltd
Address
Country
Australia
Secondary sponsor category [1] 321085 0
None
Name [1] 321085 0
Address [1] 321085 0
Country [1] 321085 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 317277 0
Central Adelaide Local Health Network HREC
Ethics committee address [1] 317277 0
Ethics committee country [1] 317277 0
Australia
Date submitted for ethics approval [1] 317277 0
25/11/2024
Approval date [1] 317277 0
22/01/2025
Ethics approval number [1] 317277 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 140542 0
A/Prof Devendra Hiwase
Address 140542 0
Haematology Clinical Trials Royal Adelaide Hospital Port Road Adelaide SA 5000
Country 140542 0
Australia
Phone 140542 0
+61 871742709
Fax 140542 0
Email 140542 0
[email protected]
Contact person for public queries
Name 140543 0
Joanna Cole
Address 140543 0
South Australian Health and Medical Research Institute PO Box 11060 Adelaide, South Australia 5001
Country 140543 0
Australia
Phone 140543 0
+61 8 81284374
Fax 140543 0
Email 140543 0
[email protected]
Contact person for scientific queries
Name 140544 0
Daniel Thomas
Address 140544 0
South Australian Health and Medical Research Institute PO Box 11060 Adelaide, South Australia 5001
Country 140544 0
Australia
Phone 140544 0
+61 8 8128 4317
Fax 140544 0
Email 140544 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No
No IPD sharing reason/comment: Individual patient data will not be shared publicly. Aggregate patient data and final results will be presented in the final report (de-identified).



What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.