Alemtuzumab for ANCA Associated Refractory Vasculitis

Phase 4

• Conditions: Vasculitis; Microscopic Polyangiitis; Granulomatosis With Polyangiitis; Wegener's
• Interventions: Drug: Alemtuzumab

• Registration Number: NCT01405807
• Lead Sponsor: Cambridge University Hospitals NHS Foundation Trust

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-02
• Status Verified: 2011-07
• Study First Submitted: 2011-07-27
• Study First Submitted QC: 2011-07-28
• Last Update Submitted: 2011-07-28
• Study First Posted: 2011-07-29
• Last Update Posted: 2011-07-29
• Primary Completion: 2014-03
• Study Completion: 2014-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 24

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Alemtuzumab - high dose (60mg)	Alemtuzumab	Alemtuzumab 30mg will be administered on Day 1 and Day 2 at 0 and 6 months
Alemtuzumab - low dose (30mg)	Alemtuzumab	Alemtuzumab 15mg will be administered on Day 1 and Day 2 at 0 and 6 months

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
Combined damage assessment (CDA) scores	12 months
Non severe adverse events	12 months
Cumulative dose of corticosteroids	12 months
Time to remission	6 months	Complete and partial
Relapse	12 months
Change in SF-36	12 months

Trial Locations

Locations (1)

Addenbrooke's Hospital, University of Cambridge NHS Foundation Trust; 🇬🇧 Cambridge, United Kingdom