Mild Alzheimer's disease MedDRA version: 8.1 Level: LLT Classification code 10001896 Term: Alzheimer's disease
Conditions
Interventions
Product Code: GSK933776A
Pharmaceutical Form: Injection*
Pharmaceutical form of the placebo: Injection*
Route of administration of the placebo: Intravenous use
Sponsors
GlaxoSmithKline Research and Development
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female subject with mild Alzheimer's Disease (AD) with MMSE score 18-26 inclusive at the screening visit. 2. Age 55 to = 80 years 3. Females must be post-menopausal (i.e. >24 months without menstrual period) or surgically sterile. Female subjects who have been post-menopausal for =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. History and/or evidence of any other central nervous system (CNS) disorder that could be interpreted as a cause of dementia 2. Hachinski Ischaemia Score >4 3. Subjects currently living in a nursing home. 4. Subjects who are unable to provide informed consent due to cognitive status 5. Screening brain MRI with one or more of the following conditions: a) not consistent with AD b) has evidence of other CNS conditions listed in criterion 1 c) shows more than minimal vascular changes d) shows more than 3 microhaemorrage lesions 6. Focal findings on the neurological exam (excluding changes attributable to peripheral injury or AD). 7. Untreated abnormal result of any of the following tests: vitamin B12, syphilis serology, thyroid stimulating hormone (TSH), where this is thought to be the cause of, or to contribute to the severity of, the subject’s dementia. 8. Any contraindications to lumbar puncture. 9. History or evidence of significant psychiatric illness such as schizophrenia or bipolar affective disorder or significant neurological disease other than AD, including epilepsy, that in the opinion of the Investigator may affect cognition or would interfere with participation in the study, or Hamilton Psychiatric Rating Scale for Depression (HAM D) (17 item) score >12. 10. TIA/stroke in the last 3 years, type 1 or type 2 diabetes mellitus, active cardiovascular disease or other uncontrolled risk factors for stroke. 11. History or evidence of any significant autoimmune disease or disorder. 12. History of seizures (excluding febrile seizures in childhood), current blood clotting or bleeding disorder or conditions that predispose to these, current clinically significant systemic illness or significant infection within 30 days (e.g. chronic persistent or acute infection). 13. Treatment with cholinesterase inhibitors is prohibited unless therapy was instituted at least 3 months prior to the administration of GSK933776A, was at stable dosage in the 2 months preceding, subject is free from any clinically significant side effects attributable to the drug that, in the opinion of the investigator, would preclude participation in the trial and that subject and caregiver agree that, barring unforeseen circumstances, the same regimen will be continued for the duration of the trial. 14. Subjects who have discontinued cholinesterase inhibitors, memantine, cognitive enhancing agents, or drugs that potentially affect cognition in the 60 days prior to screening. 15. Unless maintained on a stable dose regimen for at least 30 days prior to screening, any other medications with the potential to affect cognition other than those mentioned in #13.A single dose of a short acting benzodiazepine is allowed at MRI and PET screening provided that the dose is given more than 24 hours before cognitive testing. 16. Use of drugs with platelet antiaggregant or anti-coagulant properties (excluding the use of aspirin 325 mg/day or less 18. History of or current chronic use of systemic steroids or other immunosuppressants. 19. Prior participation in clinical investigations involving therapeutic monoclonal antibodies or proteins derived from monoclonal antibodies or any investigations of treatments or use of experimental medications for AD or any other investigational medication or device within 60 days prior to screening or within 5 half-lives of use of such a medication prior to screening, whichever is longer. 20. Systolic blood pressure >165 mmHg or d
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety and tolerability of GSK933776A after single and multiple dose intravenous administration in patients with Alzheimer’s disease;Secondary Objective: • To assess the pharmacokinetics of GSK933776A in plasma after single and multiple dose (3) administration in patients with Alzheimer’s disease. • To assess the pharmacodynamic activity effect of GSK933776A on free Abeta42 and total Abeta42 in plasma and CSF after single and multiple dose (3) administration in patients with Alzheimer’s disease. • To investigate the ability of GSK933776A to alter the expression of markers previously reported to reflect disease progression or severity in plasma and/or CSF, in response to GSK933776A administration. • To identify new biomarkers associated with pharmacodynamic drug response and/or toxicity. • To assess the immunogenicity of GSK933776A after single and multiple dose (3) intravenous administration in patients with Alzheimer’s disease.;Primary end point(s): •Adverse events. • Changes suggesting potential adverse events detected in the physical and neurological examination, brain MRI, cognitive status, laboratory parameters, ECG and vital signs. | — |
Countries
Sweden
Outcome results
None listed