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

Modulation of Beta-amyloid Levels in CSF and Plasma by GSK933776 in Patients With Mild Alzheimer's Disease or Mild Cognitive Impairment

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

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Biological: GSK933776; Biological: GSK933776; Biological: GSK933776

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 Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	22 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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.	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.	three months

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2010
• Primary Completion (Actual): December 8, 2011
• Study Completion (Actual): December 8, 2011

Study Registration Dates

• First Submitted: August 4, 2011
• First Submitted That Met QC Criteria: August 25, 2011
• First Posted (Estimate): August 29, 2011

Study Record Updates

• Last Update Posted (Actual): June 14, 2017
• Last Update Submitted That Met QC Criteria: June 13, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Alzheimer's disease; CSF sampling; Amyloid beta levels
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: 113043

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.

Study Data/Documents

1. Study Protocol
   Information identifier: 113043
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Dataset Specification
   Information identifier: 113043
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Individual Participant Data Set
   Information identifier: 113043
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Statistical Analysis Plan
   Information identifier: 113043
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Informed Consent Form
   Information identifier: 113043
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Annotated Case Report Form
   Information identifier: 113043
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Clinical Study Report
   Information identifier: 113043
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register