Clinical trial NCT01405807: Alemtuzumab for ANCA Associated Refractory Vasculitis
Official title: Alemtuzumab for ANCA Associated Refractory Vasculitis - a Study of Safety and Efficacy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Vasculitis
Microscopic Polyangiitis
Granulomatosis With Polyangiitis
Wegener's
Keywords: Vasculitis
ANCA
Refractory
Lead sponsor: Cambridge University Hospitals NHS Foundation Trust
Sponsor class: OTHER
First posted: 2011-07-29
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Proportion of patients with a vasculitis response at 6 months
timeFrame: 6 months
measure: Proportion of patients with a severe adverse event
timeFrame: 6 months
Secondary outcomes:
measure: Proportion of patients with treatment failure
timeFrame: 12 months
measure: Combined damage assessment (CDA) scores
timeFrame: 12 months
measure: Non severe adverse events
timeFrame: 12 months
measure: Cumulative dose of corticosteroids
timeFrame: 12 months
measure: Time to remission
timeFrame: 6 months
measure: Relapse
timeFrame: 12 months
measure: Change in SF-36
timeFrame: 12 months
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital, University of Cambridge NHS Foundation Trust
Study officials:
affiliation: Cambridge University Hospitals NHS Foundation Trust
name: David RW Jayne, MD MRCP
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gopaluni S, Smith R, Goymer D, Cahill H, Broadhurst E, Wallin E, McClure M, Chaudhry A, Jayne D. Alemtuzumab for refractory primary systemic vasculitis-a randomised controlled dose ranging clinical trial of efficacy and safety (ALEVIATE). Arthritis Res Ther. 2022 Apr 1;24(1):81. doi: 10.1186/s13075-022-02761-6.