Granulomatosis With Polyangiitis, Microscopic Polyangiitis, Vasculitis, Wegener's
Conditions
Keywords
Vasculitis, ANCA, Refractory
Brief summary
Overview: This open label, randomized, multi-centre study will enroll and treat 24 patients with refractory AAV. Aims: To determine the clinical response and severe adverse event rates associated with alemtuzumab therapy among patients with relapsing or refractory ANCA associated vasculitis (AAV). Hypothesis: Treatment with alemtuzumab induces sustained remission in AAV and will reduce immunosuppressive and steroid exposure.
Interventions
DRUGAlemtuzumab
Alemtuzumab will be administered on Day 1 and Day 2 at 0 and 6 months
Sponsors
Cambridge University Hospitals NHS Foundation Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. A diagnosis of AAV, according to a standardized definition 2. Active vasculitis with at least one severe or three non severe items of BVAS/WG activity (equivalent to BVAS/WG\>3) 3. Previous therapy with either cyclophosphamide or methotrexate, in combination with prednisolone for at least 3 months.
Exclusion criteria
1. Age less than 18 or greater than 60 years 2. Creatinine \> 150μmol/l (1.7mg/dl) 3. Total white count \< 4x109/l or lymphocyte count \< 0.5x109/l, or IgG \< 5g/L, or neutrophil count \< 1.5x109/l. 4. Severe lung haemorrhage with hypoxia (\<85% on room air) 5. Severe gastrointestinal, central nervous system or cardiac vasculitis 6. Previous therapy with: 1. Alemtuzumab at any time 2. IVIg, infliximab, etanercept, adalimumab, abatacept, anti-thymocyte globulin or plasma exchange in past three months 3. Rituximab within the past 6 months 7. Intensive care unit requirement 8. Active infection with HIV, hepatitis B or hepatitis C or other infection requiring parenteral or long-term oral antibiotics 9. History of ITP or platelet count at screening below 50,000 x 106/l 10. Pregnancy or inadequate contraception in pre-menopausal women 11. Breast feeding 12. Any condition judged by the investigator that would cause the study to be detrimental to the patient. 13. Any other multisystem autoimmune disease including Churg Strauss angiitis, systemic lupus erythematosus, anti-GBM disease and cryoglobulinaemia 14. Any previous or current history of malignancy (other than resected basal cell carcinoma)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients with a vasculitis response at 6 months | 6 months | Response includes patients in complete and partial remission. Complete remission (CR) is defined as a BVAS/WG of 0 for at least one month. Partial response (PR) is the absence of severe BVAS/WG items and at least 50% fall in BVAS/WG score from baseline. |
| Proportion of patients with a severe adverse event | 6 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Non severe adverse events | 12 months | — |
| Cumulative dose of corticosteroids | 12 months | — |
| Proportion of patients with treatment failure | 12 months | Treatment failure is defined as the failure to achieve a vasculitis response by six months or a vasculitis relapse between 6 and 12 months |
| Relapse | 12 months | — |
| Change in SF-36 | 12 months | — |
| Time to remission | 6 months | Complete and partial |
| Combined damage assessment (CDA) scores | 12 months | — |
Countries
United Kingdom
Contacts
Primary ContactDavid RW Jayne, MD FRCP
Backup ContactRona M Smith, MA MRCP
Outcome results
None listed