Effect of LY2062430 on the Progression of Alzheimer's Disease (EXPEDITION)

• Change from baseline to endpoint in Alzheimer's Disease Assessment Scale—Cognitive subscore (ADAS-Cog11) [ Time Frame: Baseline, 80 weeks ]
• Change from baseline to endpoint in Alzheimer's Disease Cooperative Study—Activities of Daily Living Inventory (ADCS-ADL) [ Time Frame: Baseline, 80 weeks ]

• Change from baseline to endpoint in Clinical Dementia Rating—Sum of Boxes (CDR-SB) [ Time Frame: Baseline, 80 weeks ]
• Change from baseline to endpoint in Neuropsychiatric Inventory (NPI) [ Time Frame: Baseline, 80 weeks ]
• Change from baseline to endpoint in volumetric magnetic resonance imaging (vMRI) [ Time Frame: Baseline, 80 weeks ]
• Change from baseline to endpoint in Mini-Mental State Examination (MMSE) [ Time Frame: Baseline, 80 weeks ]
• Change from baseline to endpoint in Resource Utilization in Dementia—Lite (RUD-Lite) [ Time Frame: Baseline, 80 weeks ]
• Change from baseline to endpoint in EuroQol 5-Dimensional Health-related Quality of Life Scale Proxy version (EQ-5D Proxy) [ Time Frame: Baseline, 80 weeks ]
• Change from baseline to endpoint in Quality of Life in Alzheimer's Disease (QoL-AD) [ Time Frame: Baseline, 80 weeks ]
• Change from baseline to endpoint in plasma LY2062430 to investigate a relationship between plasma LY2062430 and plasma A Beta levels. [ Time Frame: Baseline, 80 weeks ]
• Change from baseline to endpoint in plasma A Beta [ Time Frame: Baseline, 80 weeks ]

Alzheimer's disease (AD) is an age-related degenerative disorder of the brain, characterized by progressive decline in cognitive function and ability to perform activities of daily living, and ultimately can lead to death due to complications of the disease. AD is thought to be caused by an excess of A-Beta amyloid, a sticky protein in the brain that forms amyloid plaques. Treatments that slow the synthesis or deposition of A-Beta amyloid, or that increase clearance, might be expected to slow the progression of AD.

LY2062430 (solanezumab) is a humanized anti-A Beta peptide immunoglobulin G-1 (IgG1) monoclonal antibody being developed for the treatment of AD. The primary hypothesis being tested is that LY2062430 will slow cognitive and functional decline in AD as compared with placebo. Each patient's participation will last approximately 19 months. Patients taking approved AD medications may participate in this study and continue taking these medications during the study.

• Drug: LY2062430
  400 mg intravenously (IV) every 4 weeks for 80 weeks
  Other Names:

  • A Beta Antibody
  • Solanezumab (*USAN adopted name, INN pending)
• Drug: Placebo
  intravenously (IV) every 4 weeks for 80 weeks

• Experimental: LY2062430
  Intervention: Drug: LY2062430
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

• Liu-Seifert H, Siemers E, Price K, Han B, Selzler KJ, Henley D, Sundell K, Aisen P, Cummings J, Raskin J, Mohs R; Alzheimer’s Disease Neuroimaging Initiative. Cognitive Impairment Precedes and Predicts Functional Impairment in Mild Alzheimer's Disease. J Alzheimers Dis. 2015;47(1):205-14. doi: 10.3233/JAD-142508.
• Henley DB, Dowsett SA, Chen YF, Liu-Seifert H, Grill JD, Doody RS, Aisen P, Raman R, Miller DS, Hake AM, Cummings J. Alzheimer's disease progression by geographical region in a clinical trial setting. Alzheimers Res Ther. 2015 Jun 25;7(1):43. doi: 10.1186/s13195-015-0127-0. eCollection 2015.
• Liu-Seifert H, Siemers E, Sundell K, Price K, Han B, Selzler K, Aisen P, Cummings J, Raskin J, Mohs R. Cognitive and functional decline and their relationship in patients with mild Alzheimer's dementia. J Alzheimers Dis. 2015;43(3):949-55. doi: 10.3233/JAD-140792.
• Doody RS, Thomas RG, Farlow M, Iwatsubo T, Vellas B, Joffe S, Kieburtz K, Raman R, Sun X, Aisen PS, Siemers E, Liu-Seifert H, Mohs R; Alzheimer's Disease Cooperative Study Steering Committee; Solanezumab Study Group. Phase 3 trials of solanezumab for mild-to-moderate Alzheimer's disease. N Engl J Med. 2014 Jan 23;370(4):311-21. doi: 10.1056/NEJMoa1312889.

Inclusion Criteria:

• Meets criteria for mild to moderate Alzheimer's Disease (AD) with Mini-Mental State Examination score of 16 through 26 at screening
• Modified Hachinski Ischemia Scale score of less than or equal to 4
• Geriatric Depression Scale score of less than or equal to 6
• A magnetic resonance imaging (MRI) or computerized tomography (CT) scan in the last 2 years with no findings inconsistent with a diagnosis of AD
• If receiving concurrent AD treatment, must be on the medication for at least 4 months at a stable dose for at least 2 months prior to randomization

Exclusion Criteria:

• Has serious or unstable illness(es)
• Does not have a reliable caregiver who is in frequent contact with patient (at least 10 hours per week)
• Meets National Institute of Neurological Disorders and Stroke/Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS/AIREN) criteria for vascular dementia
• Does not have good venous access, such that intravenous (IV) drug delivery would be difficult
• Has had multiple episodes of head trauma or history within the last 5 years of a serious infectious disease affecting the brain
• Has allergies to humanized monoclonal antibodies
• Chronic alcohol and/or drug abuse within the past 5 years
• Has any contraindications for MRI studies
• Requires treatment with another monoclonal antibody