ANCA-associated vasculitis Circulatory System
Conditions
Interventions
ObiVas is a randomised, phase II, double-blind controlled trial. Participants will be randomised to one of two treatment groups in a 1:1 ratio and receive obinutuzumab (2 x 1000 mg iv infusions, two w
Sponsors
Cambridge Clinical Trials Unit
Eligibility
Sex/Gender
All
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Capable of giving signed informed consent 2. Participants must be aged 18 years old and over at the time of signing the informed consent form. 3. Have a diagnosis of AAV (granulomatosis with polyangiitis or microscopic polyangiitis), according to the definitions of the Chapel Hill Consensus Conference (35). 4. PR3 ANCA positivity by ELISA at screening. 5. Have active disease defined by one major or three minor disease activity items on the Birmingham Vasculitis Activity Score for Wegener’s (BVAS/WG). 6. Women of child-bearing potential (WOCBP) must agree to use effective contraception methods and agree to follow these methods for at least 18 months after the last dose of rituximab or obinutuzumab. 7. Has received at least two doses of any COVID-19 vaccination.
Exclusion criteria
Exclusion criteria: 1. Women who are pregnant, plan to become pregnant or breast feed during the trial. 2. Current participation in any other interventional treatment trials. 3. Compliance: is unlikely to comply with trial visits based on investigator judgment. 4. MPO ANCA or anti–GBM antibody positivity by ELISA during screening. 5. Presence of pulmonary haemorrhage with hypoxia. 6. Estimated glomerular filtration rate (eGFR) 2.5x upper limit of normal (ULN). 17. Active bleeding disorders, and/or inability to support interruption to anticoagulant or anti-platelet therapies for nasal biopsy. 18. Severe nasal deformity precluding endoscopic assessment/biopsy of postnasal space 19. Severe heart failure (New York Heart Association Class IV) or other severe, uncontrolled cardiac disease. 20. Have a history of a major organ transplant or hematopoietic stem cell/marrow transplant. 21. Have an acute or chronic infection requiring management as follows: 21.1. Currently on any treatment for a chronic infection such as pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster, or atypical mycobacteria 21.2. Hospitalisation solely for treatment of proven infection requiring parenteral (IV or IM) antibiotics (antibacterials, antivirals, antifungals, or anti-parasitic agents) within 60 days of Day 1. NB Hospitalisation for a participant with active vasculitis with co-existent infection requiring IV or IM antibiotics is permitted. 21.3. Proven severe infection requiring outpatient treatment with parenteral (IV or IM) antibiotics (antibacterials, antivirals, antifungals, or anti-parasitic agents) within 60 days of Day 1. Prophylactic anti-infective treatment is allowed. Precautionary PO/IV antibiotics in a participant with active vasculitis is permitted. 22. Positive human immunodeficiency virus (HIV) antibody test. 23. Positive serology for Hepatitis B (HB), defined as: (i) HB surface antigen positive (HBsAg+) OR (ii) HB core antibody positive (HBcAb+). 24. Positive Hepatitis C (HCV) antibody test. 25. Have clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to vasculitis which, in the opinion of the principal investigator, could confound the results of the trial or put the participant at undue risk. 26. Have a planned surgical procedure, laboratory abnormality, or condition that, in the opinion of the principal investigator, makes the participant unsuitable for the trial. Prior/Concomitant Therapy: 27. Live vaccine(s) within 30 days prior to Day 1, or plans to receive live vaccines during the trial. 28. Have received any anti-CD20 (or any other B cell depleting therapies including alemtuzumab) within 12 months of Day 1. 29.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measure as of 21/06/2024: Relative percentage change in live single nasal CD19+ B cells in the nasal lymphoid compartment measured using spectral flow cytometry between baseline and week 26 Previous primary outcome measure: Relative percentage change in nasal CD19+ B cell number measured using flow cytometry at baseline and at week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 21/06/2024: 1. Relative percentage change in nasal B and T cell subsets measured using spectral flow cytometry between baseline and week 26 2. Relative percentage change from baseline in blood B, T, NK cells and subsets of interest measured using spectral flow cytometry at weeks 12, 26, 39, 52, 65 and 78 3. Incidence of participants with detectable peripheral B cells measured using spectral flow cytometry at weeks 12, 26, 39, 52, 65 and 78 4. Incidence of participants with PR3-ANCA negativity measured using ELISA at weeks 12, 26, 39, 52, 65 and 78 5. Time to PR3-ANCA rise measured using ELISA 6. Incidence of participants in sustained remission (relapse-free) at weeks 12, 26, 39, 52, 65 and 78 (remission defined as a Birmingham Vasculitis Activity Score for Wegener’s Granulomatosis (BVAS-WG) =1 with daily prednisone dose =7.5 mg) 7. Time to remission defined using BVAS-WG 8. Time to first relapse in those who have achieved remission defined using BVAS-WG 9. Time to first major or second minor relapse in those who have achieved remission defined using BVAS-WG 10. Cumulative exposure to corticosteroids between groups (steroid dose calculations) from baseline to week 78 11. Incidence of participants with serious adverse events (SAEs) reported at week 78 12. Incidence of SAEs reported from consent to week 78 13. Incidence and severity of AEs of special interest (AESIs) reported from consent to week 78 Previous secondary outcome measures: 1. Tissue B and T cell subsets measured using flow cytometry at baseline and at week 12 2. Blood B and T cell subsets measured using flow cytometry at baseline and at weeks 12, 26, 39, 52, 65 and 78 3. B cell reconstitution in the blood measured by flow cytometry at weeks 12, 26, 39, 52, 65 and 78 in all patients 4. PR3 ANCA titres measured using enzyme-linked immunosorbent assays (ELISA) at baseline and at weeks 12, 26, 39, 52, 65 and 78 5. Clinical efficacy measured during patient consultati | — |
Countries
United Kingdom
Contacts
Public ContactKim Mynard
Outcome results
None listed