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

Study Description

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Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Alzheimer's Disease	Biological: GSK933776	Phase 1

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	19 participants
Allocation:	Non-Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Other
Official Title:	Modulation of Beta-amyloid Levels in CSF and Plasma by GSK933776 in Patients With Mild Alzheimer's Disease or Mild Cognitive Impairment
Actual Study Start Date :	May 19, 2010
Actual Primary Completion Date :	December 8, 2011
Actual Study Completion Date :	December 8, 2011

Arms and Interventions

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Arm	Intervention/treatment
Experimental: GSK933776 1mg/kg; single dose	Biological: GSK933776; 1mg/kg dose group
Experimental: GSK933776 0.1 or 3mg/kg; single dose	Biological: GSK933776; 3mg/kg dose group
Experimental: GSK933776 3 or 6mg/kg; single dose	Biological: GSK933776; 6mg/kg dose group

Outcome Measures

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Primary Outcome Measures :

1. 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 [ Time Frame: 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 :

1. 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 [ Time Frame: Two months ]
2. 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 [ Time Frame: 22 hours ]
3. Estimated pharmacokinetic parameters of AUC, Cmax and Tmax in CSF and plasma at multiple time points with various intervals. [ Time Frame: three months ]
4. To assess the safety and tolerability after single dose of GSK933776 administration. [ Time Frame: 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.

Eligibility Criteria

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Ages Eligible for Study:	55 Years to 85 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Locations

Germany
GSK Investigational Site
Mannheim, Baden-Wuerttemberg, Germany, 68159
GSK Investigational Site
Tuebingen, Baden-Wuerttemberg, Germany, 72076
GSK Investigational Site
Ulm, Baden-Wuerttemberg, Germany, 89081
GSK Investigational Site
Muenchen, Bayern, Germany, 81675
GSK Investigational Site
Aachen, Nordrhein-Westfalen, Germany, 52074
Sweden
GSK Investigational Site
Malmö, Sweden, SE-212 24
GSK Investigational Site
Stockholm, Sweden, se-141 86

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:	GSK Clinical Trials	GlaxoSmithKline

More Information

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Additional Information:

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.  Results for study 113043 can be found on the GSK Clinical Study Register. 

Study Data/Documents: Study Protocol 

Identifier: 113043
For additional information about this study please refer to the GSK Clinical Study Register

Dataset Specification 

Identifier: 113043
For additional information about this study please refer to the GSK Clinical Study Register

Individual Participant Data Set 

Identifier: 113043
For additional information about this study please refer to the GSK Clinical Study Register

Statistical Analysis Plan 

Identifier: 113043
For additional information about this study please refer to the GSK Clinical Study Register

Informed Consent Form 

Identifier: 113043
For additional information about this study please refer to the GSK Clinical Study Register

Annotated Case Report Form 

Identifier: 113043
For additional information about this study please refer to the GSK Clinical Study Register

Clinical Study Report 

Identifier: 113043
For additional information about this study please refer to the GSK Clinical Study Register

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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-β 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.

Leyhe T, Andreasen N, Simeoni M, Reich A, von Arnim CA, Tong X, Yeo A, Khan S, Loercher A, Chalker M, Hottenstein C, Zetterberg H, Hilpert J, Mistry P. Modulation of β-amyloid by a single dose of GSK933776 in patients with mild Alzheimer's disease: a phase I study. Alzheimers Res Ther. 2014 Apr 9;6(2):19. doi: 10.1186/alzrt249. eCollection 2014.

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT01424436 History of Changes
Other Study ID Numbers:	113043
First Posted:	August 29, 2011
Last Update Posted:	June 14, 2017
Last Verified:	June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
Plan Description:	Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Keywords provided by GlaxoSmithKline:

CSF sampling; Alzheimer's disease; Amyloid beta levels

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases	Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders