Effect of LY2062430 on the Progression of Alzheimer's Disease (EXPEDITION2)

• ClinicalTrials.gov Identifier: NCT00904683
• Recruitment Status: Completed
• First Posted: May 20, 2009
• Last Update Posted: December 13, 2012
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: May 18, 2009
• First Posted Date: May 20, 2009
• Last Update Posted Date: December 13, 2012
• Study Start Date: May 2009
• Actual Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: December 11, 2012): Change from Baseline to Week 80 in Alzheimer's Disease Assessment Scale - Cognitive Subscore 14-Item Scale (ADAS-Cog14) [ Time Frame: Baseline, Week 80 ]

Original Primary Outcome Measures (submitted: May 18, 2009)

• 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 ]

Current Secondary Outcome Measures (submitted: December 11, 2012)

• Change from Baseline to Week 80 in Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score [ Time Frame: Baseline, Week 80 ]
• Change from Baseline to Week 80 in Neuropsychiatric Inventory (NPI) Score [ Time Frame: Baseline, Week 80 ]
• Change from Baseline to Week 80 in volumetric Magnetic Resonance Imaging (vMRI) [ Time Frame: Baseline, Week 80 ]
• Change from Baseline to Week 80 in Mini-Mental State Examination (MMSE) Score [ Time Frame: Baseline, Week 80 ]
• Change from Baseline to Week 80 in Resource Utilization in Dementia - Lite (RUD-Lite) Score [ Time Frame: Baseline, Week 80 ]
• Change from Baseline to Week 80 in EuroQol 5-Dimensional Health-related Quality of Life Scale Proxy version (EQ-5D Proxy) Score [ Time Frame: Baseline, Week 80 ]
• Change from Baseline to Week 80 in Quality of Life in Alzheimer's Disease (QoL-AD) Score [ Time Frame: Baseline, Week 80 ]
• Change from Baseline to Week 80 in Plasma Amyloid Beta Levels [ Time Frame: Baseline, Week 80 ]
• Change from Baseline to Week 80 in Alzheimer's Disease Assessment Scale - Cognitive Subscore 11-Item and 12-Item Scale (ADAS-Cog11 and ADAS-Cog12) [ Time Frame: Baseline, Week 80 ]
• Change from Baseline to Week 80 in Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL) Score [ Time Frame: Baseline, Week 80 ]

Original Secondary Outcome Measures (submitted: May 18, 2009)

• 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 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Effect of LY2062430 on the Progression of Alzheimer's Disease
• Official Title: Effect of Passive Immunization on the Progression of Alzheimer's Disease: LY2062430 Versus Placebo

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Alzheimer's Disease

Intervention

• 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

Study Arms

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

Publications *

• Reed C, Belger M, Dell'Agnello G, Kahle-Wrobleski K, Sethuraman G, Hake A, Raskin J, Henley D. Representativeness of European clinical trial populations in mild Alzheimer's disease dementia: a comparison of 18-month outcomes with real-world data from the GERAS observational study. Alzheimers Res Ther. 2018 Apr 3;10(1):36. doi: 10.1186/s13195-018-0360-4.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 11, 2012): 1040
• Original Estimated Enrollment (submitted: May 18, 2009): 1000
• Actual Study Completion Date: June 2012
• Actual Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 55 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, France, Germany, Italy, Japan, Korea, Republic of, Poland, Russian Federation, Spain, Sweden, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT00904683
• Other Study ID Numbers: 11934; H8A-MC-LZAN ( Other Identifier: Eli Lilly and Company )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Eli Lilly and Company
• Original Responsible Party: Chief Medical Officer, Eli Lilly
• Current Study Sponsor: Eli Lilly and Company
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559) Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

• PRS Account: Eli Lilly and Company
• Verification Date: December 2012