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

Primary Purpose

Alzheimer's Disease

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
GSK933776
GSK933776
GSK933776
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Alzheimer's Disease focused on measuring CSF sampling, Alzheimer's disease, Amyloid beta levels

Eligibility Criteria

55 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

GSK933776 1mg/kg

GSK933776 0.1 or 3mg/kg

GSK933776 3 or 6mg/kg

Arm Description

single dose

single dose

single dose

Outcomes

Primary Outcome Measures

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
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

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
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
Estimated pharmacokinetic parameters of AUC, Cmax and Tmax in CSF and plasma at multiple time points with various intervals.
To assess the safety and tolerability after single dose of GSK933776 administration.
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.

Full Information

First Posted
August 4, 2011
Last Updated
June 13, 2017
Sponsor
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT01424436
Brief Title
Modulation of Abeta Levels by GSK933776 in Alzheimer's Disease Patient
Official Title
Modulation of Beta-amyloid Levels in CSF and Plasma by GSK933776 in Patients With Mild Alzheimer's Disease or Mild Cognitive Impairment
Study Type
Interventional

2. Study Status

Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
May 19, 2010 (Actual)
Primary Completion Date
December 8, 2011 (Actual)
Study Completion Date
December 8, 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease
Keywords
CSF sampling, Alzheimer's disease, Amyloid beta levels

7. Study Design

Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
GSK933776 1mg/kg
Arm Type
Experimental
Arm Description
single dose
Arm Title
GSK933776 0.1 or 3mg/kg
Arm Type
Experimental
Arm Description
single dose
Arm Title
GSK933776 3 or 6mg/kg
Arm Type
Experimental
Arm Description
single dose
Intervention Type
Biological
Intervention Name(s)
GSK933776
Intervention Description
1mg/kg dose group
Intervention Type
Biological
Intervention Name(s)
GSK933776
Intervention Description
3mg/kg dose group
Intervention Type
Biological
Intervention Name(s)
GSK933776
Intervention Description
6mg/kg dose group
Primary Outcome Measure Information:
Title
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
Description
To compare the changes of amyloid beta levels between the baseline (9 hours) and after single dose of GSK933776 iv administration of 13 hours
Time Frame
22 hours
Secondary Outcome Measure Information:
Title
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
Title
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
Title
Estimated pharmacokinetic parameters of AUC, Cmax and Tmax in CSF and plasma at multiple time points with various intervals.
Time Frame
three months
Title
To assess the safety and tolerability after single dose of GSK933776 administration.
Description
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.
Time Frame
three months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Mannheim
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
68159
Country
Germany
Facility Name
GSK Investigational Site
City
Tuebingen
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
72076
Country
Germany
Facility Name
GSK Investigational Site
City
Ulm
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
89081
Country
Germany
Facility Name
GSK Investigational Site
City
Muenchen
State/Province
Bayern
ZIP/Postal Code
81675
Country
Germany
Facility Name
GSK Investigational Site
City
Aachen
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
52074
Country
Germany
Facility Name
GSK Investigational Site
City
Malmö
ZIP/Postal Code
SE-212 24
Country
Sweden
Facility Name
GSK Investigational Site
City
Stockholm
ZIP/Postal Code
se-141 86
Country
Sweden

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
Citations:
PubMed Identifier
25789616
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.
Results Reference
derived
PubMed Identifier
24716469
Citation
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 beta-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.
Results Reference
derived
Links:
URL
https://www.clinicalstudydatarequest.com
Description
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
Available IPD and Supporting Information:
Available IPD/Information Type
Study Protocol
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
113043
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Dataset Specification
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
113043
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Individual Participant Data Set
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
113043
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Statistical Analysis Plan
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
113043
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Informed Consent Form
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
113043
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Annotated Case Report Form
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
113043
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Clinical Study Report
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
113043
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register

Learn more about this trial

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

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