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

NCT01424436 | Completed Phase 1

• 1 other identifier: 113043
• Study Type: interventional
• Target: 19
• Locations: 2 countries
• Sites: 7

Brief Summary

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

Conditions

Alzheimer's Disease

Keywords

CSF sampling; Alzheimer's disease; Amyloid beta levels

Outcome Measures

Primary Outcomes (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

  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 Outcomes (4)

• 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.

  three months

Study Arms (3)

GSK933776 1mg/kg

EXPERIMENTAL

single dose

Biological: GSK933776

GSK933776 0.1 or 3mg/kg

EXPERIMENTAL

single dose

Biological: GSK933776

GSK933776 3 or 6mg/kg

EXPERIMENTAL

single dose

Biological: GSK933776

Interventions

GSK933776 BIOLOGICAL

1mg/kg dose group

GSK933776 1mg/kg

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (7)

GSK Investigational Site

Mannheim, Baden-Wurttemberg, 68159, Germany

Location

GSK Investigational Site

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

GSK Investigational Site

Ulm, Baden-Wurttemberg, 89081, Germany

Location

GSK Investigational Site

Munich, Bavaria, 81675, Germany

Location

GSK Investigational Site

Aachen, North Rhine-Westphalia, 52074, Germany

Location

GSK Investigational Site

Malmo, SE-212 24, Sweden

Location

GSK Investigational Site

Stockholm, se-141 86, Sweden

Location

Related Publications (2)

• 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.

  PMID: 25789616 DERIVED

• 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.

  PMID: 24716469 DERIVED

Related 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.
• Results for study 113043 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

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

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2011
• First Posted: August 29, 2011
• Study Start: May 19, 2010
• Primary Completion: December 8, 2011
• Study Completion: December 8, 2011
• Last Updated: June 14, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will share

Locations

DE (5); SE (2)