Modulation of Abeta Levels by GSK933776 in Alzheimer's Disease Patient

Phase 1

Completed

• Conditions: Alzheimer's Disease
• Interventions: Biological: GSK933776

• Registration Number: NCT01424436
• Lead Sponsor: GlaxoSmithKline

Brief Summary

Modulation of beta-amyloid levels in CSF and plasma by GSK933776 in patients with mild Alzheimer's disease or mild cognitive impairment

Detailed Description

This is a phase I, an open label, single dose and parallel group study to assess short term pharmacodynamics and safety of GSK933776. The effect on the beta amyloid levels will be assessed in early (MCI) and mild Alzheimer's disease (AD) patients after a single dose of GSK933776 by i.v. administration.

Study Timeline

• Study Start: 2010-05-19
• Study First Submitted: 2011-08-04
• Study First Submitted QC: 2011-08-25
• Study First Posted: 2011-08-29
• Primary Completion: 2011-12-08
• Study Completion: 2011-12-08
• Status Verified: 2017-06
• Last Update Submitted: 2017-06-13
• Last Update Posted: 2017-06-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

Inclusion Criteria

• Probable mild Alzheimer's disease (MMSE 20-26) or mild cognitive impairment
• Increase in total tau or p-tau in CSF
• Decrease in amyloid beta in CSF
• Stable dose of cholinesterase inhibitors, memantine or selegine or no treatment
• Body weight less than 120 kg
• Willingness to comply with contraceptive methods if self or partner is of child-bearing potential

Exclusion Criteria

• Any other cause of dementia
• Other significant neurologic or psychiatric illness
• Hachinski Ischemia Score >4
• More than 3 microbleeds on MRI
• Type 2 diabetes not controlled by diet
• Risk of cerebrovascular disease, cerebral haemorrhage or stroke
• History of systemic autoimmune disease
• Use of platelet anti-aggregates or anti-coagulants (Aspirin up to 325 mg/day is allowable)
• Use of chronic corticosteroids
• Uncontrolled hypertension in spite of antihypertensive medications
• Renal or hepatic insufficiency or clinically significant anaemia
• In nursing home care
• Contraindications to lumbar puncture or MRI
• Prior participation in therapeutic studies only after adequate wash-out period

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GSK933776 0.1 or 3mg/kg	GSK933776	single dose
GSK933776 3 or 6mg/kg	GSK933776	single dose
GSK933776 1mg/kg	GSK933776	single dose

Primary Outcome Measures

Name	Time	Method
The temporal changes of amyloid beta levels in CSF after GSK933776 single dose administration in the patients with Alzheimer's disease and Mild Cognitive impairment	22 hours	To compare the changes of amyloid beta levels between the baseline (9 hours) and after single dose of GSK933776 iv administration of 13 hours

Secondary Outcome Measures

Name	Time	Method
The temporal changes of total and free amyloid beta levels in plasma after GSK933776 single dose administration in the patients with Alzheimer's disease and Mild Cognitive impairment	Two months
Estimated pharmacokinetic parameters of AUC, Cmax and Tmax in CSF and plasma at multiple time points with various intervals.	three months
To assess the safety and tolerability after single dose of GSK933776 administration.	three months	The safety and tolerability measures are performed at screening, dosing day and follow up. The assessments included: • Adverse event reporting and safety laboratory data. • CNS Safety: MRI and MMSE. • CVS safety: ECG and vital signs. •Anti-GSK933776 antibodies.
The temporal changes of Tau and phosphor Tau - 181 levels in CSF after GSK933776 single dose administration in the patients with Alzheimer's disease and Mild Cognitive impairment	22 hours

Trial Locations

Locations (1)

GSK Investigational Site; 🇸🇪 Stockholm, Sweden