Alemtuzumab for ANCA Associated Refractory Vasculitis

Vasculitis Clinical Trial

— ALEVIATE  

Official title:

Alemtuzumab for ANCA Associated Refractory Vasculitis - a Study of Safety and Efficacy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01405807
• Other study ID #: AL1.1
• Secondary ID: 2009-017087-17
• Status: Recruiting
• Phase: Phase 4
• First received: July 27, 2011
• Last updated: July 28, 2011
• Start date: February 2011
• Est. completion date: March 2014

Study information

• Verified date: July 2011
• Source: Cambridge University Hospitals NHS Foundation Trust
• Contact: David RW Jayne, MD FRCP
• Phone: 00441223586796
• Email: dj106[@]cam.ac.uk
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: March 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Granulomatosis With Polyangiitis
• Microscopic Polyangiitis
• Systemic Vasculitis
• Vasculitis
• Wegener Granulomatosis
• Wegener's

Intervention

Drug:
• Alemtuzumab
Alemtuzumab will be administered on Day 1 and Day 2 at 0 and 6 months

Locations

Country	Name	City	State
United Kingdom	Addenbrooke's Hospital, University of Cambridge NHS Foundation Trust	Cambridge

Sponsors (1)

Lead Sponsor	Collaborator
Cambridge University Hospitals NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with a vasculitis response at 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.	6 months	No
Primary	Proportion of patients with a severe adverse event		6 months	Yes
Secondary	Proportion of patients with treatment failure	Treatment failure is defined as the failure to achieve a vasculitis response by six months or a vasculitis relapse between 6 and 12 months	12 months	No
Secondary	Combined damage assessment (CDA) scores		12 months	No
Secondary	Non severe adverse events		12 months	Yes
Secondary	Cumulative dose of corticosteroids		12 months	Yes
Secondary	Time to remission	Complete and partial	6 months	No
Secondary	Relapse		12 months	No
Secondary	Change in SF-36		12 months	No