Clinical trial NCT00459550: A Clinical Study to Assess Single and Repeat Doses of a New Medication (GSK933776) in Patients With Alzheimer's Disease
Official title: A Randomised, Single-Blind, Placebo-Controlled Study to Investigate the Safety, Tolerability, Immunogenicity, Pharmacokinetics and Pharmacodynamics of Intravenous Infusion of GSK933776 in Patients With Alzheimer's Disease.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alzheimer's Disease
Keywords: Alzheimer's Disease
First Time in Human (FTIH) Study
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-04-12
Enrollment: 50
Sex: ALL
Minimum age (years): 55
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A study to investigate the safety and tolerability of both single and multiple intravenous administration of GSK933776 in patients with Alzheimer's Disease.


Eligibility criteria: Inclusion criteria:

* Male or female subject with a clinical diagnosis of probable Alzheimer's disease
* Subject has mild AD with Mini Mental State Examination (MMSE) score 18-26 inclusive at the screening visit.
* Age between 55 and 80 years.
* Female subjects must be post-menopausal or surgically sterile.
* Male subjects whose partner is of child-bearing potential or have been menopausal for \<2 years must use an adequate form of contraception.
* Subject has the ability to comply with procedures for cognitive and other testing \& is fluent in the language used for the administration of the cognitive tests.
* 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.
* Subject has provided full written informed consent prior to the performance of any protocol-specified procedure.
* Caregiver has provided a full written informed consent on his/her own behalf prior to the performance of any protocol-specified procedure.

Exclusion criteria:

* History and/or evidence of any other central nervous system (CNS) disorder that could be interpreted as a cause of dementia.
* Subjects currently living in a nursing home.
* Subjects who are unable to provide informed consent due to cognitive status
* Screening brain MRI with 1 or more of the following conditions: not consistent with AD, evidence of other CNS conditions, shows more than minimal vascular changes, more than 3 microhaemorrhage lesions.
* Focal findings on the neurological exam.
* Any contraindication to lumbar puncture.
* History or evidence of significant psychiatric illness such as schizophrenia or bipolar affective disorder or significant neurological disease other than AD.
* TIA/stroke in the last 3 years, type 1 or type 2 diabetes mellitus, active cardiovascular disease, or other uncontrolled risk factors for stroke.
* Current or recent drug or alcohol abuse or dependence or recent or remote history of the same if that could be a contributing factor to the dementia.
* History or evidence of any significant autoimmune disease or disorder.
* History of seizures (excluding febrile seizures in childhood), current blood clotting or bleeding disorder or conditions that predispose to these (e.g. cancer), current clinically significant systemic illness or significant infection within 30 days that is likely to result in deterioration of the subject's condition or affect the subject's safety during the study.
* History of cerebral amyloid antiopathy and/or hypertensive cerebral haemorrhage or with a known risk of intercerebral haemorrhage/microhaemorrhage.
* Treatment which cholinesterase inhibitors, memantine or selegiline unless the therapy was instituted at least 3 months prior to the administration of GSK933776, at a stable dosage in the 2 months prior and the same regimen will be continued for the duration of the trial and the subject is free from any clinically significant side effects attributable to the drug.
* Subjects who have discontinued cholinesterase inhibitors, memantine, cognitive enhancing agents, or drugs that potentially affect cognition in the 60 days prior to screening.
* Unless maintained on a stable dose regimen for at least 30 days prior to screening, any other medications with the potential to affect cognition.
* Use of drugs with platelet anti-aggregant or anti-coagulant properties (excluding the use of aspirin 325 mg/day or less), anticonvulsants for seizures or narcotic medication.
* History of or current chronic use of systemic steroids or other immunosuppressants.
* 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.
* Contraindications for MRI: pacemaker, aneurysm clips, artificial heart valves, other metal foreign body, claustrophobia, etc.
* Smoking more than 20 cigarettes or equivalent per day.

Primary outcomes:
measure: Adverse events. Changes suggesting potential adverse events detected in the physical & neurological examination, brain MRI, cognitive status, laboratory parameters, ECG & vital signs.
timeFrame: 12 weeks for Part A; 34 weeks in Part B
Secondary outcomes:
measure: Plasma pharmacokinetic parameters of GSK933776. Pharmacodynamic effects of GSK 933776. CSF detectable levels of GSK933776. Effects of GSK933776 on plasma and CSF biomarkers. Titre & neutralising activity of anti-GSK933776 antibodies. Exploratory PET scan
timeFrame: 12 weeks for Part A; 34 weeks in Part B
Other outcomes:
Locations:
city: Herston
country: Australia
facility: GSK Investigational Site
state: Queensland
city: Heidelberg Heights
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Fremantle
country: Australia
facility: GSK Investigational Site
state: Western Australia
city: Lørenskog
country: Norway
facility: GSK Investigational Site
city: Malmö
country: Sweden
facility: GSK Investigational Site
city: Mölndal
country: Sweden
facility: GSK Investigational Site
city: Stockholm
country: Sweden
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Andreasen N, Simeoni M, Ostlund H, Lisjo PI, Fladby T, Loercher AE, Byrne GJ, Murray F, Scott-Stevens PT, Wallin A, Zhang YY, Bronge LH, Zetterberg H, Nordberg AK, Yeo AJ, Khan SA, Hilpert J, Mistry PC. First administration of the Fc-attenuated anti-beta amyloid antibody GSK933776 to patients with mild Alzheimer's disease: a randomized, placebo-controlled study. PLoS One. 2015 Mar 19;10(3):e0098153. doi: 10.1371/journal.pone.0098153. eCollection 2015.