ALEVIATE.

Study name	Alemtuzumab for ANCA Associated Refractory Vasculitis ‐ a Study of Safety and Efficacy
Methods	A open label, randomised, multi‐centre study with two arms: 1. arm: Alemtuzumab ‐ high dose (60mg) 2. arm: Alemtuzumab ‐ low dose (30mg)
Participants	Inclusion criteria: Active AAV with >=one severe or >=three non severe items of BVAS/WG (BVAS/WG>3). Previous treatment with cyclophosphamide or methotrexate, and prednisolone for >= three months. Exclusion criteria: Age < 18 or > 60 years. Creatinine above 150μmol/l (1.7mg/dl). Total white blood cells count below 4x109/l or lymphocyte count below 0.5x109/l, or Immunoglobulin G below 5g/L, or neutrophil count below 1.5x109/l. Severe lung haemorrhage with hypoxia (<85% on room air). Severe gastrointestinal, central nervous system or cardiac vasculitis. Previous therapy with: Any alemtuzumab Within the past 3 months: IVIg, infliximab, etanercept, adalimumab, abatacept, anti‐thymocyte globulin or plasma exchange Within the past 6 months: rituximab. 7. Required intensive care unit treatment. 8. Active infection with HIV, hepatitis B or hepatitis C or other infection which requires parenteral or long‐term oral antibiotics. 9. History of idiopathic thrombocytopenic purpura or platelet count below 50,000 x 106/l at screening. 10. Pregnancy or nursing or not adequate contraception in pre‐menopausal women. 11. Any condition which can be associated with detrimental effect of the study to the participant. 12. Any other multisystem autoimmune disease, such as Churg Strauss angiitis, systemic lupus erythematosus,anti‐glomerular basement membrane disease and cryoglobulinaemia. 13. Any previous or current history of cancer (other than resected basal cell carcinoma).
Interventions	Arm 1: Alemtuzumab (Campath 1H)‐ high dose (60mg) ‐ Alemtuzumab will be administered on Day 1 and Day 2 at 0 and 6 months. Arm 2: Alemtuzumab (Campath 1H)‐ low dose (30mg) ‐ Alemtuzumab will be administered on Day 1 and Day 2 at 0 and 6 months.
Outcomes	Major outcome: Proportion of patients with a vasculitis response at 6 months ‐ includes patients in complete and partial remission. Complete remission is defined as a BVAS/WG of 0 for >=one month. Partial response is defined as the absence of severe BVAS/WG items and >= 50% fall in BVAS/WG score from baseline. Minor outcomes: Proportion of patients with treatment failure within 12 months defined as the failure to achieve a response by six months or a relapse between 6 and 12 months. Combined damage assessment scores within 12 months. Non severe AEs within 12 months. Cumulative dose of corticosteroids within 12 months. Time to complete and partial remission within 6 months . Relapse within 12 months. Change in SF‐36 within 12 months.
Starting date	February 2011
Contact information	David Jayne FMedSci Professor of Clinical Autoimmunity Department of Medicine School of Clinical Medicine University of Cambridge CB2 2QQ Tel 01223 325039 dj106@cam.ac.uk
Notes	We received information that the trial has completed recruitment but follow‐up is ongoing.