- Trials closed
A study of the immune response to vaccination in MS patients treated with alemtuzumab.
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system that affects as many as 2.5 million people worldwide and 90,000 people in the United Kingdom. It is believed to arise from the interplay of polygenic inherited susceptibility and environmental agents that remain unidentified. It is approximately twice as common among women as men. Worldwide, its prevalence varies geographically and, within the same country, between different racial groups. Prevalence is highest amongst Caucasians in countries distant from the Equator, for instance Scotland and Scandinavia. Peak incidence is within the third and fourth decades.
This is a study of the efficacy of vaccination in patients with multiple sclerosis who have been treated with the investigational medicine, alemtuzumab. Alemtuzumab (previously known as Campath-1H) is a therapeutic monoclonal antibody that causes long lasting depletion of T lymphocytes. It is licensed for the treatment of chronic lymphocytic leukaemia (CLL), but has also been used in various autoimmune diseases, and in transplantation medicine. It has been used as an experimental treatment of multiple sclerosis in Cambridge, UK, since 1991. The latest phase 2 trial, published in the NEJM in October 2008, demonstrated that it is the most effective treatment of multiple sclerosis to date, when given early in the relapsing-remitting phase of the illness. The principal adverse effect is autoimmunity (thyroid in 20% and immune thrombocytopenia purpura in 3%). There was also a slightly increased risk of infections, especially viral, after alemtuzumab treatment. Two phase 3 trials, comparing alemtuzumab with standard licensed therapies, recruiting a total of 1500 patients are currently on-going.
The issue of the effectiveness of vaccination and retained immunological memory to infections is important for patients with multiple sclerosis treated with alemtuzumab because: (i) they are young adults who may well be exposed to infections in young children or who require vaccinations for travel abroad however (ii) alemtuzumab produces a dramatic and profound lymphopaenia, which may compromise immunological memory or the ability to respond appropriately to a vaccination. It takes a median of 6 years before CD4+ numbers are fully restored 2. There has been no previous study of the effectiveness of vaccinations after alemtuzumab treatment.
We propose to test the effectiveness of three vaccines in patients who have received alemtuzumab as part of the approved phase 2 or phase 3 trials:
Menitorix; a Haemophilus influenzae type b and Meningococcal group C vaccine (T-dependent neo-antigens)
Pneumovax II; a pneumococcal capsular polysaccharide vaccine (T-cell independent antigen)
Revaxis; a vaccine containing tetanus toxoid, diphtheria toxoid and inactivated polio (T-dependent recall antigens).
These are inactivated or subunit vaccines, which are considered safe in immunocompromised patients.
Main inclusion criteria
Male or non-pregnant, non-lactating female patients, 18 to 50 years of age (inclusive)
Diagnosis of MS using the McDonald’s criteria
Received alemtuzumab at least 4 weeks previously
If receiving Revaxis must have been previously vaccinated against tetanus (for the tetanus vaccine to stimulate the desired recall response)
Main exclusion criteria
Previously received Haemophilus b or pneumococcal vaccines or have had Haemophilus or pneumococcal disease (these antigens are intended to be novel to the subject’s immune system)
Allergy to a component in any of the vaccines
Previous or current immune thrombocytopaenic purpura (ITP) or haemolytic anaemia.
Received a diphtheria or tetanus toxoid vaccine within the last 5 years; only applicable if the patient will be given Revaxis (vaccination recommended after 5 years to minimise adverse events)
Guillain-Barré syndrome or brachial neuritis due to a previous vaccine
Acute severe febrile illness
Funders and sponsors
Funders: University of Cambridge
Prof Alasdair Coles
Clinical Trials Manager: Dr Paula Kareclas
Telephone: 01223 596473 | Email: firstname.lastname@example.org