The primary aim of the study is to determine the safety and tolerability of etanercept in
subjects with Alzheimer's Disease. The effects of etanercept on cognitive, behavioural,
functional and immunological outcomes will be examined as secondary aims.
Minimum age: 55 Years.
Maximum age: N/A.
- Male or female patients aged > 54 years
- Have a minimum of 7 years of education
- Be able to hear, read, write and perform study neuropsychological tests in English
- Have adequate visual and auditory acuity to allow neuropsychological testing based on
the research clinician's judgement
- Fulfil Diagnostic & Statistical Manual (DSM-IV-TR)criteria for diagnosis of dementia
of the Alzheimer type
- Have a diagnosis of probable Alzheimer's Disease (National Institute of Neurological
and Communicative Disorders and Stroke and the Alzheimer's Disease and Related
Disorders Association (NINCDS-ADRDA) criteria)
- Mini Mental State Examination (MMSE) score < 27 and > 10 points.
- To be currently taking and have been taking a cholinesterase inhibitor for a minimum
period of 3 months prior to the day of inclusion into the study or to have been not
been taking a cholinesterase inhibitor for a minimum period of 3 months prior to the
day of inclusion into the study
- Have an informant who spends at least 24 hours per week with the patient and may be a
close friend or a neighbour, not necessarily a close relative, spouse, son or
daughter. He/she should be the same throughout the study and should be present at all
visits. If it becomes necessary, a change of informant can be made but this must be
- Inability or refusal to provide informed consent from patient or caregiver
- Absence of informant
- Unlikely to cooperate in the study, not able to attend scheduled examinations and
visits, or not able to follow study instructions
- Participation in another study with administration of any investigational drug in the
previous 3 months or already enrolled in another study
- Parkinson's Disease, Dementia with Lewy Bodies or clinically significant Parkinsonian
- Vascular disorder (modified Hachinski Ischaemic Scale score > 4)
- Recent Transient Ischaemic Attack (TIA) - within the last 3 months
- Signs of major cerebrovascular disease on MRI or CT scan, if performed prior to entry
into study (i. e. presence of infarction in greater than 25% of white matter, more
than 1 lacune within basal ganglia, more than 2 lacunes in white matter)
- Any other previous or ongoing chronic or recurrent disease of the central nervous
system, including demyelinating disease or psychiatric diseases, that may have an
impact on cognitive performance, left to the research clinician's judgement
- Any of the following laboratory abnormalities at the screening visit:
i) Clinically significant Vitamin B12 levels less than the lower limit of normal ii)
Clinically significant folate levels less than the lower limit of normal iii)
Clinically significant thyroid-stimulating hormone (TSH) levels greater than the
upper limit of normal and a clinically significant free thyroxine (FT4) level lower
than the lower limit of normal
- Patients with previous or present history of severe or unstable medical conditions
(e. g. hypertension, diabetes left to the research clinician's judgement)
- Current alcohol >35 units per week for men, or >28 units per week for women, or drug
abuse at the discretion of the research clinician
- Surgical intervention planned during the study period.
- Treatment with immunosuppressive drugs and/or oral prednisone greater than 10mg/day
within the past 90 days
- Treatment with Memantine within the past 3 months
- Vaccination or immunization with any live vaccine (eg: polio, rubella, yellow fever)
or the pneumococcal vaccine within the past 30 days.
- Pregnancy or breast feeding.
- Severe hepatic, renal or cardiac disease.
- Previous use of a Tumour Necrosis Factor-alpha (TNFα) agent.
- Known skin photosensitivity.
- Infection in past 4 weeks or active infection.
- Heart failure: New York Heart Association (NYHA) Grade 3-4.
- History of blood disorders or current WCC ≤ 3. 5 x 109/l; platelet count ≤ 100x109/l ;
Hb ≤ 10g/dl.
- Active or latent tuberculosis
- Rheumatoid arthritis; psoriasis; psoriatic arthritis or ankylosing spondylitis
- Septic arthritis in past 12 months
- Sepsis of prosthesis in past 12 months
- Chronic leg ulcers
- Indwelling urinary catheter
- Pulmonary fibrosis
- History of neoplasms / malignancies in past 5 years
- Pre-malignant conditions including Barrett's oesophagus; cervical dysplasia; large
- Any relevant acute or chronic abnormality detected during the physical and
neurological examinations. Electrocardiogram (ECG) or laboratory tests likely to
interfere with the study evaluations in the research clinician's judgement
- Previous exposure to amyloid vaccines, monoclonal antibodies or intravenous
immunoglobulins meant to treat Alzheimer's disease