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.
Overview
- Phase
- Phase 1
- Intervention
- GSK933776
- Conditions
- Alzheimer's Disease
- Sponsor
- GlaxoSmithKline
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- Adverse events. Changes suggesting potential adverse events detected in the physical & neurological examination, brain MRI, cognitive status, laboratory parameters, ECG & vital signs.
- Status
- Completed
- Last Updated
- 8 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Part A
Part A will be a single-blind, single dose, placebo controlled, dose escalation study in up to five consecutive cohorts of Alzheimers Disease subjects. Each subject will receive a single infusion of GSK933776 or placebo. The dose for the first cohort will be 0.001 mg/kg. The proposed nominal doses for subsequent cohorts are 0.01, 0.1, 0.5 and 3 mg/kg, but these may be altered based on the outcome of the safety, tolerability, pharmacodynamic and pharmacokinetic data of the preceding group(s). The maximum possible dose will be 20 mg/kg, although the planned top dose is 18 mg/kg
Intervention: GSK933776
Part A
Part A will be a single-blind, single dose, placebo controlled, dose escalation study in up to five consecutive cohorts of Alzheimers Disease subjects. Each subject will receive a single infusion of GSK933776 or placebo. The dose for the first cohort will be 0.001 mg/kg. The proposed nominal doses for subsequent cohorts are 0.01, 0.1, 0.5 and 3 mg/kg, but these may be altered based on the outcome of the safety, tolerability, pharmacodynamic and pharmacokinetic data of the preceding group(s). The maximum possible dose will be 20 mg/kg, although the planned top dose is 18 mg/kg
Intervention: Placebo to match GSK933776
Part B
Part B will be a single-blind, repeat dose, placebo controlled dose escalation design. It is proposed that there will be initially 3 cohorts of AD subjects. However up to 5 cohorts may be recruited if required in order to characterise GSK933776 fully.Each cohort will consist of eight subjects (six active, two placebo) who will each receive a maximum of three infusions of GSK933776 or placebo. Dosing in Part B may proceed in parallel with Part A following satisfactory review of minimum data sets as below: First cohort in Part B: at least 3 weeks' data from the Part A dose that is the same dose level as that planned for Part B Second cohort in Part B: at least 3 weeks PK data and 8 weeks safety data following the first dose from all the subjects on active treatment in the preceding Part B cohort plus a satisfactory outcome of the PIB Subsequent cohorts in Part B: at least 3 weeks PK data and 8 weeks safety data follow
Intervention: GSK933776
Part B
Part B will be a single-blind, repeat dose, placebo controlled dose escalation design. It is proposed that there will be initially 3 cohorts of AD subjects. However up to 5 cohorts may be recruited if required in order to characterise GSK933776 fully.Each cohort will consist of eight subjects (six active, two placebo) who will each receive a maximum of three infusions of GSK933776 or placebo. Dosing in Part B may proceed in parallel with Part A following satisfactory review of minimum data sets as below: First cohort in Part B: at least 3 weeks' data from the Part A dose that is the same dose level as that planned for Part B Second cohort in Part B: at least 3 weeks PK data and 8 weeks safety data following the first dose from all the subjects on active treatment in the preceding Part B cohort plus a satisfactory outcome of the PIB Subsequent cohorts in Part B: at least 3 weeks PK data and 8 weeks safety data follow
Intervention: Placebo to match GSK933776
Outcomes
Primary Outcomes
Adverse events. Changes suggesting potential adverse events detected in the physical & neurological examination, brain MRI, cognitive status, laboratory parameters, ECG & vital signs.
Time Frame: 12 weeks for Part A; 34 weeks in Part B
Secondary Outcomes
- 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(12 weeks for Part A; 34 weeks in Part B)