Alemtuzumab for ANCA Associated Refractory Vasculitis (ALEVIATE)

NHS Foundation Trust

Status and phase: Unknown; Phase 4

Conditions: Granulomatosis With Polyangiitis; Wegener's; Vasculitis; Microscopic Polyangiitis

Treatments: Drug: Alemtuzumab

Study type: Interventional

Funder types: Other

Identifiers

NCT01405807

AL1.1

2009-017087-17 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 24 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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24 participants in 2 patient groups

Alemtuzumab - high dose (60mg)

Experimental group

Description:

Alemtuzumab 30mg will be administered on Day 1 and Day 2 at 0 and 6 months

Treatment:

Drug: Alemtuzumab

Alemtuzumab - low dose (30mg)

Experimental group

Description:

Alemtuzumab 15mg will be administered on Day 1 and Day 2 at 0 and 6 months

Treatment:

Drug: Alemtuzumab