Alemtuzumab for ANCA Associated Refractory Vasculitis (ALEVIATE)

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

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.

Study Overview

Study Type

Interventional

Enrollment (Anticipated)

24

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: David RW Jayne, MD FRCP
  • Phone Number: 00441223586796
  • Email: dj106@cam.ac.uk

Study Contact Backup

Study Locations

      • Cambridge, United Kingdom, CB20QQ
        • Recruiting
        • Addenbrooke's Hospital, University of Cambridge NHS Foundation Trust
        • Contact:
          • David RW Jayne, MD FRCP
          • Phone Number: 00441223586796
          • Email: dj106@cam.ac.uk
        • Principal Investigator:
          • David RW Jayne, MD FRCP

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 58 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Alemtuzumab - high dose (60mg)
Alemtuzumab 30mg will be administered on Day 1 and Day 2 at 0 and 6 months
Alemtuzumab will be administered on Day 1 and Day 2 at 0 and 6 months
Other Names:
  • Campath 1H
Experimental: Alemtuzumab - low dose (30mg)
Alemtuzumab 15mg will be administered on Day 1 and Day 2 at 0 and 6 months
Alemtuzumab will be administered on Day 1 and Day 2 at 0 and 6 months
Other Names:
  • Campath 1H

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patients with a vasculitis response at 6 months
Time Frame: 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
Proportion of patients with a severe adverse event
Time Frame: 6 months
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relapse
Time Frame: 12 months
12 months
Proportion of patients with treatment failure
Time Frame: 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
12 months
Combined damage assessment (CDA) scores
Time Frame: 12 months
12 months
Non severe adverse events
Time Frame: 12 months
12 months
Cumulative dose of corticosteroids
Time Frame: 12 months
12 months
Time to remission
Time Frame: 6 months
Complete and partial
6 months
Change in SF-36
Time Frame: 12 months
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: David RW Jayne, MD MRCP, Cambridge University Hospitals NHS Foundation Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2011

Primary Completion (Anticipated)

March 1, 2014

Study Completion (Anticipated)

March 1, 2014

Study Registration Dates

First Submitted

July 27, 2011

First Submitted That Met QC Criteria

July 28, 2011

First Posted (Estimate)

July 29, 2011

Study Record Updates

Last Update Posted (Estimate)

July 29, 2011

Last Update Submitted That Met QC Criteria

July 28, 2011

Last Verified

July 1, 2011

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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