A randomised, single-blind, placebo-controlled study to investigate the safety, tolerability, immunogenicity, pharmacokinetics and pharmacodynamics of intravenous infusion of GSK933776A in patients with Alzheimer’s disease

• Conditions: Mild Alzheimer's disease; MedDRA version: 8.1Level: LLTClassification code 10001896Term: Alzheimer's disease

• Registration Number: EUCTR2006-004014-41-SE
• Lead Sponsor: GlaxoSmithKline Research and Development

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-10-03
• Last Update Posted: 1 May 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 122

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 < 2 years must undertake pregnancy testing (ßhCG) at Visit 1, which must be negative and must use an adequate form of non-hormonal contraceptive (e.g. barrier method).
4. Males whose partner is of child-bearing potential or have been menopausal for <2 years must use an adequate form of contraception (e.g. barrier method).
5. Subject has the ability to comply with procedures for cognitive and other testing, including MRI scans, and is fluent in the language used for the administration of the cognitive tests.
6. Subject lives with (or has substantial periods of contact with) a permanent caregiver who is willing to oversee the subject's compliance with protocol-specified procedures and study medication, and report on subject's status.
7. Fluency in local language and evidence of adequate pre-morbid intellectual functioning. Subject must have adequate visual and auditory abilities to perform all aspects of the cognitive and functional assessments.
8. In the opinion of the Investigator, the subject and the caregiver will be compliant and have a high probability of completing the study.
9. Subject has provided full written informed consent prior to the performance of any protocol-specified procedure.
10. Caregiver has provided a full written informed consent on his/her own behalf prior to the performance of any protocol-specified procedure.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified