A Study to Evaluate the Efficacy and Safety of ABBV-8E12 in Participants With Early Alzheimer's Disease

Alzheimer's Disease Clinical Trial

Official title:

A Phase 2 Multiple Dose, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of ABBV-8E12 in Subjects With Early Alzheimer's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02880956
• Other study ID #: M15-566
• Secondary ID: 2016-001634-10
• Status: Completed
• Phase: Phase 2
• Start date: January 26, 2017
• Est. completion date: July 28, 2021

Study information

• Verified date: August 2022
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study seeks to evaluate the efficacy and safety of ABBV-8E12 in participants with early Alzheimer's disease (AD).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 453
• Est. completion date: July 28, 2021
• Est. primary completion date: March 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 85 Years

Eligibility

Inclusion Criteria:

• Subject who meets the National Institute on Aging and the Alzheimer's Association

(NIA-AA) clinical criteria for mild cognitive impairment or probable AD, and have:

• Clinical Dementia Rating (CDR)-Global Score of 0.5
• Mini-Mental State Examination (MMSE) score of 22 to 30, inclusive
• Repeatable Battery for the Assessment of Neuropsychological Status-Delayed Memory Index (RBANS - DMI) score of 85 or lower
• Subject has a positive amyloid positron emission tomography (PET) scan.
• Subject has a Modified Hachinski Ischemic Scale (MHIS) score of = 4.
• The subject has an identified, reliable, study partner (e.g., family member).
• If using medications to treat symptoms related to AD, doses must be stable for at least 12 weeks prior to randomization.

Exclusion Criteria:

• Subject has any contraindications or inability to tolerate brain magnetic resonance imaging (MRI), PET scans or lumbar puncture.
• Subject has evidence of any other clinically significant neurological disorder other than early AD.
• In the opinion of the investigator, the subject has any clinically significant or uncontrolled medical or psychiatric illness, or has had an infection requiring medical intervention in the past 30 days.
• Subject has had a myocardial infarction, unstable angina, stroke, transient ischemic attack or required intervention for any of these conditions within 6 months of Screening.

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• ABBV-8E12
ABBV-8E12 solution for IV infusion
• placebo for ABBV-8E12
placebo solution for intravenous (IV) infusion

Locations

Country	Name	City	State
Australia	The Kinghorn Cancer Centre /ID# 152632	Darlinghurst	New South Wales
Australia	Austin Health /ID# 152637	Heidelberg	Victoria
Australia	Australian Alzheimer's Res Fou /ID# 152634	Nedlands	Western Australia
Australia	The Royal Melbourne Hospital /ID# 202633	Parkville	Victoria
Australia	Griffith University /ID# 152635	Southport	Queensland
Australia	Neurodegenerative Disorders Research /ID# 152826	West Perth	Western Australia
Belgium	Universitair Ziekenhuis Leuven /ID# 152642	Leuven	Vlaams-Brabant
Belgium	Groupe Sante CHC - Clinique du MontLegia /ID# 152846	Liege
Belgium	UCL Saint-Luc /ID# 152847	Woluwe-Saint-Lambert	Bruxelles-Capitale
Canada	Parkwood Institute /ID# 164204	London	Ontario
Canada	Toronto Memory Program /ID# 147863	Toronto	Ontario
Denmark	Rigshospitalet /ID# 153192	Copenhagen Ø	Hovedstaden
Finland	Ita-Suomen Yliopisto /ID# 152959	Kuopio
Finland	Clinical Research Services Turku /ID# 152845	Turku	Varsinais-Suomi
Italy	IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli /ID# 152395	Brescia
Italy	Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico /ID# 152401	Milan
Italy	ASST Grande Ospedale Metropolitano Niguarda /ID# 152391	Milano
Italy	AOU di Modena /ID# 152394	Modena	Emilia-Romagna
Italy	Azienda Ospedaliera di Perugia /ID# 152397	Perugia	Umbria
Italy	Duplicate_AOU Policlinico Umberto I /ID# 163144	Rome	Lazio
Italy	Policlinico Agostino Gemelli /ID# 152396	Rome	Lazio
Netherlands	Universitair Medisch Centrum Utrecht /ID# 163576	Utrecht
New Zealand	CGM Research Trust /ID# 152827	Burwood
Spain	Fundacio ACE /ID# 152643	Barcelona
Spain	Hospital Clinic de Barcelona /ID# 152646	Barcelona
Spain	Fundacion CITA Alzheimer Fundazioa /ID# 152645	Donostia	Pais Vasco
Spain	Hospital Clinico Universitario San Carlos /ID# 153703	Madrid
Spain	Hospital Universitario 12 de Octubre /ID# 152647	Madrid
Sweden	Sahlgrenska University Hospital Molndal /ID# 154465	Molndal	Vastra Gotalands Lan
Sweden	Karolinska University Hospital Huddinge /ID# 156705	Stockholm	Stockholms Lan
United States	Integrated Neurology Services /ID# 154863	Alexandria	Virginia
United States	Atlanta Center for Medical Research /ID# 151550	Atlanta	Georgia
United States	Emory Midtown Infectious Disease Clinic /ID# 151492	Atlanta	Georgia
United States	Johns Hopkins Bayview Med Cnt /ID# 151893	Baltimore	Maryland
United States	Brigham and Women's Physicians /ID# 151882	Boston	Massachusetts
United States	Massachusetts General Hospital /ID# 151770	Boston	Massachusetts
United States	Great Lakes Clinical Trials /ID# 152754	Chicago	Illinois
United States	Kerwin Research Center /ID# 147815	Dallas	Texas
United States	NeuroStudies.net, LLC /ID# 152746	Decatur	Georgia
United States	Brain Matters Research /ID# 147796	Delray Beach	Florida
United States	Duke Cancer Center /ID# 147828	Durham	North Carolina
United States	University of Kansas Medical Center - Alzheimer's Disease Center /ID# 151554	Fairway	Kansas
United States	Neuropsychiatric Research Center of Southwest Florida /ID# 162332	Fort Myers	Florida
United States	Hattiesburg Clinic /ID# 202388	Hattiesburg	Mississippi
United States	Houston Methodist Hospital /ID# 154810	Houston	Texas
United States	McGovern Medical School /ID# 204860	Houston	Texas
United States	Indiana University /ID# 151861	Indianapolis	Indiana
United States	Irvine Clinical Research /ID# 162331	Irvine	California
United States	Mayo Clinic /ID# 151236	Jacksonville	Florida
United States	Ucsd /Id# 152467	La Jolla	California
United States	Scott Research Inc. /ID# 151880	Laurelton	New York
United States	University of Kentucky Chandler Medical Center /ID# 152753	Lexington	Kentucky
United States	Vanderbilt University Medical Center /ID# 154547	Nashville	Tennessee
United States	North Shore University Hospital /ID# 151632	New Hyde Park	New York
United States	Synexus Clinical Research US, Inc. /ID# 147804	Orlando	Florida
United States	Advocate Lutheran General Hospital /ID# 152052	Park Ridge	Illinois
United States	Banner University of Arizona Medical Center Phoenix /ID# 151536	Phoenix	Arizona
United States	Keystone Clinical Studies LLC /ID# 202305	Plymouth Meeting	Pennsylvania
United States	Oregon Health and Science University /ID# 151690	Portland	Oregon
United States	Princeton Medical Institute /ID# 152934	Princeton	New Jersey
United States	Rhode Island Hospital /ID# 151538	Providence	Rhode Island
United States	University of Utah /ID# 151858	Salt Lake City	Utah
United States	Ray Dolby Brain Health Center /ID# 154965	San Francisco	California
United States	Univ California, San Francisco /ID# 152053	San Francisco	California
United States	Southern IL Univ School of Med /ID# 151769	Springfield	Illinois
United States	Banner Sun Health Res Inst /ID# 151895	Sun City	Arizona
United States	University of South Florida /ID# 151890	Tampa	Florida
United States	Synexus Clinical Research US, Inc /ID# 151633	The Villages	Florida

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Denmark,  Finland,  Italy,  Netherlands,  New Zealand,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline Over Time in CDR-SB Score	The CDR-SB is a numeric scale used to quantify the severity of symptoms of dementia. A qualified health professional assesses a participant's cognitive and functional performance in 6 areas: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. The CDR scale gives a score from 0 to 3 for each of the 6 areas, with a lower value being desirable. The sum of these 6 areas, the CDR-SB score, can range from 0 to 18, with a lower value being desirable.	Baseline, Week 24, Week 48, Week 72, Week 96
Primary	Number of Participants With Treatment Emergent Adverse Events (TEAEs)	A TEAE was defined as an adverse event (AE) that began on or after the first study drug dose date and no more than 20 weeks after the last dose of study drug. An adverse event (AE) was defined as any untoward medical occurrence which does not necessarily have a causal relationship with this treatment. Serious AEs (SAEs) were defined as an event that results in death, is life-threatening, results in hospitalization or prolongs hospitalization, is a congenital abnormality, results in persistent or significant disability/incapacity, or is an important medical event. Events were rated in severity as mild, moderate, or severe, and were categorized as having a reasonable possibility or no reasonable possibility of relationship to study drug.	From first dose of study drug up to last dose of study drug plus 20 weeks (up to Week 112)
Secondary	Maximum Observed Serum Concentration (Cmax) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses		Day 1 (Dose 1): Pre-infusion, post-infusion (within 15 minutes), 1 and 2 hours post-infusion; Days 5 and 15. Day 85 (Dose 4): Pre-infusion (0 hour), post-infusion (within 15 minutes) and 1 and 2 hours post-infusion; Days 89 and 99.
Secondary	Time to Cmax (Tmax) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses		Day 1 (Dose 1): Pre-infusion, post-infusion (within 15 minutes), 1 and 2 hours post-infusion; Days 5 and 15. Day 85 (Dose 4): Pre-infusion (0 hour), post-infusion (within 15 minutes) and 1 and 2 hours post-infusion; Days 89 and 99.
Secondary	Serum Concentration at the End of a Dose Interval (Ctrough) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses		Day 1 (Dose 1): Pre-infusion, post-infusion (within 15 minutes), 1 and 2 hours post-infusion; Days 5 and 15. Day 85 (Dose 4): Pre-infusion (0 hour), post-infusion (within 15 minutes) and 1 and 2 hours post-infusion; Days 89 and 99.
Secondary	Half-Life (T1/2) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses	Harmonic mean is presented in the data table.	Day 1 (Dose 1): Pre-infusion, post-infusion (within 15 minutes), 1 and 2 hours post-infusion; Days 5 and 15. Day 85 (Dose 4): Pre-infusion (0 hour), post-infusion (within 15 minutes) and 1 and 2 hours post-infusion; Days 89 and 99.
Secondary	Area Under the Concentration-Time Curve From Dosing (Time 0) to Day 28 (AUC0-28) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses	The AUC0-28 for Dose 1 included the following timepoints: pre-infusion, post-infusion (within 15 min), 1 and 2 hours post-infusion, Day 5, Day 15 and Day 29 (trough level before Dose 2).; The AUC0-28 for Dose 4 included the following timepoints: Day 85 pre-infusion, post-infusion (within 15 min), 1 and 2 hours post-infusion, Day 89, Day 99 and Day 113 (trough level before Dose 5).	Day 1 (Dose 1): pre-infusion, up to Day 29 (trough level before Dose 2). Day 85 (Dose 4): pre-infusion, up to Day 113 (trough level before Dose 5). See Outcome Measure description above for complete time point details.
Secondary	Cmax/Dose for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses		Day 1 (Dose 1): Pre-infusion, post-infusion (within 15 minutes), 1 and 2 hours post-infusion; Days 5 and 15. Day 85 (Dose 4): Pre-infusion (0 hour), post-infusion (within 15 minutes) and 1 and 2 hours post-infusion; Days 89 and 99.
Secondary	AUC0-28/Dose for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses	The AUC0-28/dose for Dose 1 included the following timepoints: pre-infusion, post-infusion (within 15 min), 1 and 2 hours post-infusion, Day 5, Day 15 and Day 29 (trough level before Dose 2).; The AUC0-28/dose for Dose 4 included the following timepoints: Day 85 pre-infusion, post-infusion (within 15 min), 1 and 2 hours post-infusion, Day 89, Day 99 and Day 113 (trough level before Dose 5).	Day 1 (Dose 1): pre-infusion, up to Day 29 (trough level before Dose 2). Day 85 (Dose 4): pre-infusion, up to Day 113 (trough level before Dose 5). See Outcome Measure description above for complete time point details.
Secondary	Change From Baseline Over Time in Alzheimer's Disease Assessment Scale (14-Item) Cognition Portion (ADAS-Cog-14) Total Score	The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 [1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task] and includes 3 additional tasks [12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning], for increased sensitivity in mild cognitive impairment (MCI) patients. The Total Score of the ADAS-Cog-14 ranges from 0 to 90, with a higher score representing greater impairment.	Baseline, Week 24, Week 48, Week 72, Week 96
Secondary	Change From Baseline Over Time in ADAS-Cog-14 Comprehension of Spoken Language Score	The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 [1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task] and includes 3 additional tasks [12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning], for increased sensitivity in MCI patients. The Comprehension of Spoken Language score of the ADAS-Cog-14 ranges from 0 to 5, with a higher score representing greater impairment.	Baseline, Week 24, Week 48, Week 72, Week 96
Secondary	Change From Baseline Over Time in ADAS-Cog-14 Constructional Praxis Score	The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 [1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task] and includes 3 additional tasks [12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning], for increased sensitivity in MCI patients. The Constructional Praxis Score of the ADAS-Cog-14 ranges from 0 to 5, with a higher score representing greater impairment.	Baseline, Week 24, Week 48, Week 72, Week 96
Secondary	Change From Baseline Over Time in ADAS-Cog-14 Commands Score	The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 [1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task] and includes 3 additional tasks [12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning], for increased sensitivity in MCI patients. The Commands Score of the ADAS-Cog-14 ranges from 0 to 5, with a higher score representing greater impairment.	Baseline, Week 24, Week 48, Week 72, Week 96
Secondary	Change From Baseline Over Time in ADAS-Cog-14 Delayed Word Recall Score	The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 [1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task] and includes 3 additional tasks [12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning], for increased sensitivity in MCI patients. The Delayed Word Recall Score of the ADAS-Cog-14 ranges from 0 to 10, with a higher score representing greater impairment.	Baseline, Week 24, Week 48, Week 72, Week 96
Secondary	Change From Baseline Over Time in ADAS-Cog-14 Ideational Praxis Score	The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 [1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task] and includes 3 additional tasks [12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning], for increased sensitivity in MCI patients. The Ideational Praxis Score of the ADAS-Cog-14 ranges from 0 to 5, with a higher score representing greater impairment.	Baseline, Week 24, Week 48, Week 72, Week 96
Secondary	Change From Baseline Over Time in ADAS-Cog-14 Maze Task Score	The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 [1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task] and includes 3 additional tasks [12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning], for increased sensitivity in MCI patients. The Maze Task Score of the ADAS-Cog-14 ranges from 0 to 5, with a higher score representing greater impairment.	Baseline, Week 24, Week 48, Week 72, Week 96
Secondary	Change From Baseline Over Time in ADAS-Cog-14 Number Cancellation Score	The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 [1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task] and includes 3 additional tasks [12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning], for increased sensitivity in MCI patients. The Number Cancellation Score of the ADAS-Cog-14 ranges from 0 to 5, with a higher score representing greater impairment.	Baseline, Week 24, Week 48, Week 72, Week 96
Secondary	Change From Baseline Over Time in ADAS-Cog-14 Naming Score	The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 [1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task] and includes 3 additional tasks [12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning], for increased sensitivity in MCI patients. The Naming Score of the ADAS-Cog-14 ranges from 0 to 5 with a higher score representing greater impairment.	Baseline, Week 24, Week 48, Week 72, Week 96
Secondary	Change From Baseline Over Time in ADAS-Cog-14 Orientation Score	The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 [1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task] and includes 3 additional tasks [12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning], for increased sensitivity in MCI patients. The Orientation Score of the ADAS-Cog-14 ranges from 0 to 8, with a higher score representing greater impairment.	Baseline, Week 24, Week 48, Week 72, Week 96
Secondary	Change From Baseline Over Time in ADAS-Cog-14 Word Recall - Number of Words Not Recalled Score	The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 [1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task] and includes 3 additional tasks [12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning], for increased sensitivity in MCI patients. The Word Recall - Number of Words Not Recalled Score of the ADAS-Cog-14 ranges from 0 to 10, with a higher score representing greater impairment.	Baseline, Week 24, Week 48, Week 72, Week 96
Secondary	Change From Baseline Over Time in ADAS-Cog-14 Remember Word Recognition Instructions Score	The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 [1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task] and includes 3 additional tasks [12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning], for increased sensitivity in MCI patients. The Remember Word Recognition Instructions Score of the ADAS-Cog-14 ranges from 0 to 5, with a higher score representing greater impairment.	Baseline, Week 24, Week 48, Week 72, Week 96
Secondary	Change From Baseline Over Time in ADAS-Cog-14 Spoken Language Ability Score	The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 [1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task] and includes 3 additional tasks [12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning], for increased sensitivity in MCI patients. The Spoken Language Ability Score of the ADAS-Cog-14 ranges from 0 to 5, with a higher score representing greater impairment.	Baseline, Week 24, Week 48, Week 72, Week 96
Secondary	Change From Baseline Over Time in ADAS-Cog-14 Word Find Difficulty Spontaneous Speech Score	The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 [1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task] and includes 3 additional tasks [12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning], for increased sensitivity in MCI patients. The Word Find Difficulty Spontaneous Speech Score of the ADAS-Cog-14 ranges from 0 to 5, with a higher score representing greater impairment.	Baseline, Week 24, Week 48, Week 72, Week 96
Secondary	Change From Baseline Over Time in ADAS-Cog-14 Word Recognition Score	The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 [1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task] and includes 3 additional tasks [12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning], for increased sensitivity in MCI patients. The Word Recognition Score of the ADAS-Cog-14 ranges from 0 to 12, with a higher score representing greater impairment.	Baseline, Week 24, Week 48, Week 72, Week 96
Secondary	Change From Baseline Over Time in Functional Activities Questionnaire (FAQ) Score	The FAQ measures level of assistance (functional disability) needed for carrying out instrumental activities in daily living (iADLs). The FAQ score ranges from 0 - 30 and consists of 10 items (each scored from 0 - 3), which measure a specific iADL in the past 4-weeks: [1) writing checks, paying bills, keeping financial records; 2) assembling tax or business records; 3) shopping alone; 4) playing a game of skill; 5) making coffee or tea; 6) preparing a balanced meal; 7) keeping track of current events; 8) attending to and understanding a television program, book, or magazine; 9) remembering appointments, family occasions, medications; and 10) traveling out of the neighborhood]. Performance in each category is rated from 0 - 3 as follows: 0 - normal; 1 - has difficulty, but does by self; 2 - requires assistance; or 3 - dependent. The FAQ was administered by a trained interviewer. Higher scores indicate a greater requirement of assistance.	Baseline, Week 24, Week 48, Week 72, Week 96
Secondary	Change From Baseline Over Time in Alzheimer's Disease Cooperative Study Clinical Global Impression of Change for Mild Cognitive Impairment (ADCS-CGIC-MCI) General Condition Score	The instrument assesses the physician's global impression of change in 4 major cognitive domains. The instrument covers 4 major domains: 1. General condition , 2. Cognition, 3. Behavior, and 4. Social and daily functioning. Scoring is based on a 7-point Likert Scale: 1, marked improvement; 2, moderate improvement; 3, minimal improvement; 4, no change; 5, minimal worsening; 6, moderate worsening; 7, marked worsening. Higher score indicates greater worsening.	Baseline, Week 48, Week 96
Secondary	Change From Baseline Over Time in ADCS-CGIC-MCI Cognition Score	The instrument assesses the physician's global impression of change in 4 major cognitive domains. The instrument covers 4 major domains: 1. General condition , 2. Cognition, 3. Behavior, and 4. Social and daily functioning. Scoring is based on a 7-point Likert Scale: 1, marked improvement; 2, moderate improvement; 3, minimal improvement; 4, no change; 5, minimal worsening; 6, moderate worsening; 7, marked worsening. Higher score indicates greater worsening.	Baseline, Week 48, Week 96
Secondary	Change From Baseline Over Time in ADCS-CGIC-MCI Behavior Score	The instrument assesses the physician's global impression of change in 4 major cognitive domains. The instrument covers 4 major domains: 1. General condition , 2. Cognition, 3. Behavior, and 4. Social and daily functioning. Scoring is based on a 7-point Likert Scale: 1, marked improvement; 2, moderate improvement; 3, minimal improvement; 4, no change; 5, minimal worsening; 6, moderate worsening; 7, marked worsening. Higher score indicates greater worsening.	Baseline, Week 48, Week 96
Secondary	Change From Baseline Over Time in ADCS-CGIC-MCI Functional Abilities Score	The instrument assesses the physician's global impression of change in 4 major cognitive domains. The instrument covers 4 major domains: 1. General condition , 2. Cognition, 3. Behavior, and 4. Social and daily functioning (functional abilities). Scoring is based on a 7-point Likert Scale: 1, marked improvement; 2, moderate improvement; 3, minimal improvement; 4, no change; 5, minimal worsening; 6, moderate worsening; 7, marked worsening. Higher score indicates greater worsening.	Baseline, Week 48, Week 96
Secondary	Change From Baseline Over Time in University of California's Performance Based Skills Assessment, Brief Version (UPSA-Brief) - Total Score	The UPSA-Brief is a performance-based instrument which uses a series of tasks and roleplay scenarios to evaluate a person's functional capacity in two areas of basic living skills (i.e., financial skills and communication skills). Scores range from 0 to 100; a higher score of the UPSA-Brief is desirable.	Baseline, Week 48, Week 96
Secondary	Change From Baseline Over Time in 24-Item Alzheimer's Disease Cooperative Study/Activities of Daily Living Scale Adapted for Patients With Mild Cognitive Impairment (ADCS-MCI-ADL-24) Total Score	The ADCS-MCI-ADL-24 is a 24-item, study partner-based assessment of activities of daily living designed specifically for AD patients and is completed by a trained rater. The scale assesses functional activities such as cooking, household chores, shopping, keeping appointments, social interactions and hobbies. Items are assessed according to whether they were performed in the past 4 weeks and, if so, some items are further assessed as to whether they were performed independently, with supervision, or with physical help. Scores on the ADCS-ADL-MCI range from 0 to 69, where higher score indicates greater capability to carry out activities of daily living.	Baseline, Week 48, Week 96
Secondary	Change From Baseline Over Time in Repeatable Battery for Assessment of Neuropsychological Status (RBANS) - Total Scale Score	The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. Total score can range from 40 to 160 with a higher score representing a better outcome.	Baseline, Week 24, Week 48, Week 72, Week 96
Secondary	Change From Baseline Over Time in RBANS - Coding Total Score	The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The Coding Total Score of the RBANS ranges from 0 to 89, with a higher score representing a better outcome.	Baseline, Week 24, Week 48, Week 72, Week 96
Secondary	Change From Baseline Over Time in RBANS - Digit Span Total Score	The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The Digit Span Total Score of the RBANS ranges from 0 to 8, with a higher score representing a better outcome.	Baseline, Week 24, Week 48, Week 72, Week 96
Secondary	Change From Baseline Over Time in RBANS - Figure Copy Total Score	The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The Figure Copy Total Score of the RBANS ranges from 0 to 20, with a higher score representing a better outcome.	Baseline, Week 24, Week 48, Week 72, Week 96
Secondary	Change From Baseline Over Time in RBANS - Figure Recall Total Score	The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The Figure Recall Total Score of the RBANS ranges from 0 to 18, with a higher score representing a better outcome.	Baseline, Week 24, Week 48, Week 72, Week 96
Secondary	Change From Baseline Over Time in RBANS - List Recognition Total Score	The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The List Recognition Total Score of the RBANS ranges from 0 to 20, with a higher score representing a better outcome.	Baseline, Week 24, Week 48, Week 72, Week 96
Secondary	Change From Baseline Over Time in RBANS - List Learning Total Score	The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The List Learning Total Score of the RBANS ranges from 0 to 40, with a higher score representing a better outcome.	Baseline, Week 24, Week 48, Week 72, Week 96
Secondary	Change From Baseline Over Time in RBANS - Line Orientation Total Score	The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The Line Orientation Total Score of the RBANS ranges from 0 to 20, with a higher score representing a better outcome.	Baseline, Week 24, Week 48, Week 72, Week 96
Secondary	Change From Baseline Over Time in RBANS - List Recall Total Score	The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The List Recall Total Score of the RBANS ranges from 0 to 10, with a higher score representing a better outcome.	Baseline, Week 24, Week 48, Week 72, Week 96
Secondary	Change From Baseline Over Time in RBANS - Picture Naming Total Score	The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The Picture Naming Total Score of the RBANS ranges from 0 to 10, with a higher score representing a better outcome.	Baseline, Week 24, Week 48, Week 72, Week 96
Secondary	Change From Baseline Over Time in RBANS - Semantic Fluency Total Score	The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The Semantic Fluency Total Score of the RBANS ranges from 0 to 40, with a higher score representing a better outcome.	Baseline, Week 24, Week 48, Week 72, Week 96
Secondary	Change From Baseline Over Time in RBANS - Story Memory Total Score	The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The Story Memory Total Score of the RBANS ranges from 0 to 24, with a higher score representing a better outcome.	Baseline, Week 24, Week 48, Week 72, Week 96
Secondary	Change From Baseline Over Time in RBANS - Story Recall Total Score	The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The Story Recall Total Score of the RBANS ranges from 0 to 12, with a higher score representing a better outcome.	Baseline, Week 24, Week 48, Week 72, Week 96
Secondary	Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Total Score	The MMSE is a brief, 30-point questionnaire, administered by a trained rater, which provides a quantitative measure of cognitive status in adults and is widely used to screen for cognitive impairment and to estimate the severity of cognitive impairment at a given point in time in AD participants. The MMSE ranges from 0 to 30, with lower scores indicating greater impairment.	Baseline, Week 24, Week 48, Week 72, Week 96
Secondary	Change From Baseline Over Time in Neuropsychiatry Inventory (NPI) Total Score	The NPI is used to assess changes in the participant's behavior that occurred in a defined period of time (4 weeks). The NPI assesses 12 behavioral domains on the dimensions of frequency and severity. Frequency is rated on a scale where 0 = absent, 1 = occasionally, 2 = often, 3 = frequently, 4 = very frequently. Severity is rated on a scale where 0 = absent, 1 = mild, 2 = moderate, 3 = severe. For each of the domains, 3 scores are obtained: frequency, severity, and total (product of frequency and severity; ranges from 0 to 12, with a lower score desirable). A total NPI score can be calculated by summing the domain total scores. Total Score ranges from 0 to 144 with a lower score desirable.	Baseline, Week 24, Week 48, Week 72, Week 96
Secondary	Change From Baseline Over Time in Alzheimer's Disease Composite Score (ADCOMS) Score	ADCOMS score is a composite score which is a weighted linear combination of the selected individual scale items from ADAS-Cog-14 (see description in Outcome Measure 10) , MMSE (see description in Outcome Measure 45), and CDR-SB (see description in Outcome Measure 1) scales. The ADCOMS score ranges from 0 to 1.97, with a lower score desirable.	Baseline, Week 24, Week 48, Week 72, Week 96