Alemtuzumab for ANCA Associated Refractory Vasculitis

NCT01405807 | Unknown Phase 4

• 2 other identifiers: AL1.12009-017087-17
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Vasculitis; ANCA; Refractory

Outcome Measures

Primary Outcomes (2)

• 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

• Proportion of patients with a severe adverse event

  6 months

Secondary Outcomes (7)

• Proportion of patients with treatment failure

  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

Study Arms (2)

Alemtuzumab - high dose (60mg)

EXPERIMENTAL

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

Drug: Alemtuzumab

Alemtuzumab - low dose (30mg)

EXPERIMENTAL

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

Drug: Alemtuzumab

Interventions

Alemtuzumab DRUG

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

Also known as: Campath 1H

Alemtuzumab - high dose (60mg); Alemtuzumab - low dose (30mg)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• A diagnosis of AAV, according to a standardized definition
• Active vasculitis with at least one severe or three non severe items of BVAS/WG activity (equivalent to BVAS/WG\>3)
• Previous therapy with either cyclophosphamide or methotrexate, in combination with prednisolone for at least 3 months.

You may not qualify if:

• Age less than 18 or greater than 60 years
• Creatinine \> 150μmol/l (1.7mg/dl)
• Total white count \< 4x109/l or lymphocyte count \< 0.5x109/l, or IgG \< 5g/L, or neutrophil count \< 1.5x109/l.
• Severe lung haemorrhage with hypoxia (\<85% on room air)
• Severe gastrointestinal, central nervous system or cardiac vasculitis
• Previous therapy with:
• Alemtuzumab at any time
• IVIg, infliximab, etanercept, adalimumab, abatacept, anti-thymocyte globulin or plasma exchange in past three months
• Rituximab within the past 6 months
• Intensive care unit requirement
• Active infection with HIV, hepatitis B or hepatitis C or other infection requiring parenteral or long-term oral antibiotics
• History of ITP or platelet count at screening below 50,000 x 106/l
• Pregnancy or inadequate contraception in pre-menopausal women
• Breast feeding
• Any condition judged by the investigator that would cause the study to be detrimental to the patient.

Sponsors & Collaborators

• Cambridge University Hospitals NHS Foundation Trust: lead

Study Sites (1)

Addenbrooke's Hospital, University of Cambridge NHS Foundation Trust

Cambridge, CB20QQ, United Kingdom

RECRUITING

Related Publications (1)

• 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.

  PMID: 35365179 DERIVED

MeSH Terms

Conditions

Vasculitis; Microscopic Polyangiitis; Granulomatosis with Polyangiitis

Interventions

Alemtuzumab

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Systemic Vasculitis; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• David RW Jayne, MD MRCP

  Cambridge University Hospitals NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David RW Jayne, MD FRCP

CONTACT

00441223586796; dj106@cam.ac.uk

Rona M Smith, MA MRCP

CONTACT

00441223217259; ronasmith@doctors.net.uk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 27, 2011
• First Posted: July 29, 2011
• Study Start: February 1, 2011
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: July 29, 2011

Record last verified: 2011-07

Locations

GB (1)