Safety and Tolerability of Etanercept in Alzheimer's Disease (STEADI-09)

University of Southampton

Status and phase

Completed

Phase 2

Conditions

Alzheimer's Disease

Treatments

Other: Placebo

Biological: Etanercept

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01068353

STEADI-09

2009-013400-31 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment

41 patients

Sex

All

Ages

55+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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 clearly documented.

Exclusion criteria

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 symptoms
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 bowel polyps
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