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

Phase 2

Completed

Conditions: Alzheimer's Disease

Interventions: Drug: ABBV-8E12
Drug: placebo for ABBV-8E12

Registration Number: NCT02880956

Lead Sponsor: AbbVie

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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 453

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ABBV-8E12 2000 mg	ABBV-8E12	ABBV-8E12 2000 mg every 4 weeks for 96 weeks
Placebo	placebo for ABBV-8E12	Placebo for ABBV-8E12 every 4 weeks for 96 weeks
ABBV-8E12 300 mg	ABBV-8E12	ABBV-8E12 300 mg every 4 weeks for 96 weeks
ABBV-8E12 1000 mg	ABBV-8E12	ABBV-8E12 1000 mg every 4 weeks for 96 weeks

Primary Outcome Measures

Name	Time	Method
Change From Baseline Over Time in CDR-SB Score	Baseline, Week 24, Week 48, Week 72, Week 96	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.
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	From first dose of study drug up to last dose of study drug plus 20 weeks (up to Week 112)	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.

Secondary Outcome Measures

Name	Time	Method
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.
AUC0-28/Dose for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses	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.	* 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).
Change From Baseline Over Time in ADAS-Cog-14 Constructional Praxis Score	Baseline, Week 24, Week 48, Week 72, Week 96	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.
Change From Baseline Over Time in ADAS-Cog-14 Maze Task Score	Baseline, Week 24, Week 48, Week 72, Week 96	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.
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.
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.
Change From Baseline Over Time in ADAS-Cog-14 Comprehension of Spoken Language Score	Baseline, Week 24, Week 48, Week 72, Week 96	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.
Change From Baseline Over Time in ADAS-Cog-14 Commands Score	Baseline, Week 24, Week 48, Week 72, Week 96	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.
Change From Baseline Over Time in ADAS-Cog-14 Ideational Praxis Score	Baseline, Week 24, Week 48, Week 72, Week 96	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.
Change From Baseline Over Time in ADAS-Cog-14 Naming Score	Baseline, Week 24, Week 48, Week 72, Week 96	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.
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.
Half-Life (T1/2) 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.	Harmonic mean is presented in the data table.
Change From Baseline Over Time in Alzheimer's Disease Assessment Scale (14-Item) Cognition Portion (ADAS-Cog-14) Total Score	Baseline, Week 24, Week 48, Week 72, Week 96	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.
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	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.	* 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).
Change From Baseline Over Time in ADAS-Cog-14 Number Cancellation Score	Baseline, Week 24, Week 48, Week 72, Week 96	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.
Change From Baseline Over Time in ADAS-Cog-14 Word Recall - Number of Words Not Recalled Score	Baseline, Week 24, Week 48, Week 72, Week 96	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.
Change From Baseline Over Time in ADCS-CGIC-MCI Behavior Score	Baseline, Week 48, Week 96	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.
Change From Baseline Over Time in ADAS-Cog-14 Delayed Word Recall Score	Baseline, Week 24, Week 48, Week 72, Week 96	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.
Change From Baseline Over Time in ADAS-Cog-14 Orientation Score	Baseline, Week 24, Week 48, Week 72, Week 96	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.
Change From Baseline Over Time in ADAS-Cog-14 Remember Word Recognition Instructions Score	Baseline, Week 24, Week 48, Week 72, Week 96	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.
Change From Baseline Over Time in ADAS-Cog-14 Word Find Difficulty Spontaneous Speech Score	Baseline, Week 24, Week 48, Week 72, Week 96	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.
Change From Baseline Over Time in ADAS-Cog-14 Word Recognition Score	Baseline, Week 24, Week 48, Week 72, Week 96	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.
Change From Baseline Over Time in ADAS-Cog-14 Spoken Language Ability Score	Baseline, Week 24, Week 48, Week 72, Week 96	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.
Change From Baseline Over Time in Functional Activities Questionnaire (FAQ) Score	Baseline, Week 24, Week 48, Week 72, Week 96	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.
Change From Baseline Over Time in ADCS-CGIC-MCI Cognition Score	Baseline, Week 48, Week 96	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.
Change From Baseline Over Time in ADCS-CGIC-MCI Functional Abilities Score	Baseline, Week 48, Week 96	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.
Change From Baseline Over Time in University of California's Performance Based Skills Assessment, Brief Version (UPSA-Brief) - Total Score	Baseline, Week 48, Week 96	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.
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	Baseline, Week 48, Week 96	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.
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	Baseline, Week 48, Week 96	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.
Change From Baseline Over Time in RBANS - Figure Copy Total Score	Baseline, Week 24, Week 48, Week 72, Week 96	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.
Change From Baseline Over Time in RBANS - Line Orientation Total Score	Baseline, Week 24, Week 48, Week 72, Week 96	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.
Change From Baseline Over Time in RBANS - Picture Naming Total Score	Baseline, Week 24, Week 48, Week 72, Week 96	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.
Change From Baseline Over Time in RBANS - Semantic Fluency Total Score	Baseline, Week 24, Week 48, Week 72, Week 96	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.
Change From Baseline Over Time in RBANS - Story Memory Total Score	Baseline, Week 24, Week 48, Week 72, Week 96	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.
Change From Baseline Over Time in RBANS - Story Recall Total Score	Baseline, Week 24, Week 48, Week 72, Week 96	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.
Change From Baseline Over Time in Repeatable Battery for Assessment of Neuropsychological Status (RBANS) - Total Scale Score	Baseline, Week 24, Week 48, Week 72, Week 96	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.
Change From Baseline Over Time in RBANS - Coding Total Score	Baseline, Week 24, Week 48, Week 72, Week 96	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.
Change From Baseline Over Time in RBANS - List Learning Total Score	Baseline, Week 24, Week 48, Week 72, Week 96	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.
Change From Baseline Over Time in Alzheimer's Disease Composite Score (ADCOMS) Score	Baseline, Week 24, Week 48, Week 72, Week 96	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.
Change From Baseline Over Time in RBANS - Digit Span Total Score	Baseline, Week 24, Week 48, Week 72, Week 96	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.
Change From Baseline Over Time in RBANS - Figure Recall Total Score	Baseline, Week 24, Week 48, Week 72, Week 96	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.
Change From Baseline Over Time in RBANS - List Recognition Total Score	Baseline, Week 24, Week 48, Week 72, Week 96	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.
Change From Baseline Over Time in RBANS - List Recall Total Score	Baseline, Week 24, Week 48, Week 72, Week 96	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.
Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Total Score	Baseline, Week 24, Week 48, Week 72, Week 96	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.
Change From Baseline Over Time in Neuropsychiatry Inventory (NPI) Total Score	Baseline, Week 24, Week 48, Week 72, Week 96	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.

Trial Locations

Locations (68): Irvine Clinical Research /ID# 162331
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Irvine, California, United States
Brain Matters Research /ID# 147796
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Delray Beach, Florida, United States
Neuropsychiatric Research Center of Southwest Florida /ID# 162332
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Fort Myers, Florida, United States
Emory Midtown Infectious Disease Clinic /ID# 151492
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Atlanta, Georgia, United States
Atlanta Center for Medical Research /ID# 151550
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Atlanta, Georgia, United States
NeuroStudies.net, LLC /ID# 152746
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Decatur, Georgia, United States
Great Lakes Clinical Trials /ID# 152754
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Chicago, Illinois, United States
Advocate Lutheran General Hospital /ID# 152052
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Park Ridge, Illinois, United States
Princeton Medical Institute /ID# 152934
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Princeton, New Jersey, United States
Kerwin Research Center /ID# 147815
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Dallas, Texas, United States
McGovern Medical School /ID# 204860
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Houston, Texas, United States
Toronto Memory Program /ID# 147863
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Toronto, Ontario, Canada
Indiana University /ID# 151861
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Indianapolis, Indiana, United States
Duke Cancer Center /ID# 147828
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Durham, North Carolina, United States
University of Kansas Medical Center - Alzheimer's Disease Center /ID# 151554
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Fairway, Kansas, United States
Neurodegenerative Disorders Research /ID# 152826
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West Perth, Western Australia, Australia
Australian Alzheimer's Res Fou /ID# 152634
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Nedlands, Western Australia, Australia
Azienda Ospedaliera di Perugia /ID# 152397
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Perugia, Umbria, Italy
Universitair Ziekenhuis Leuven /ID# 152642
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Leuven, Vlaams-Brabant, Belgium
Ita-Suomen Yliopisto /ID# 152959
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Kuopio, Finland
Hattiesburg Clinic /ID# 202388
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Hattiesburg, Mississippi, United States
Banner Sun Health Res Inst /ID# 151895
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Sun City, Arizona, United States
Austin Health /ID# 152637
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Heidelberg, Victoria, Australia
The Royal Melbourne Hospital /ID# 202633
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Parkville, Victoria, Australia
Massachusetts General Hospital /ID# 151770
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Boston, Massachusetts, United States
UCL Saint-Luc /ID# 152847
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Woluwe-Saint-Lambert, Bruxelles-Capitale, Belgium
Groupe Sante CHC - Clinique du MontLegia /ID# 152846
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Liege, Belgium
Clinical Research Services Turku /ID# 152845
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Turku, Varsinais-Suomi, Finland
Universitair Medisch Centrum Utrecht /ID# 163576
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Utrecht, Netherlands
Brigham and Women's Physicians /ID# 151882
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Boston, Massachusetts, United States
Duplicate_AOU Policlinico Umberto I /ID# 163144
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Rome, Lazio, Italy
IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli /ID# 152395
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Brescia, Italy
AOU di Modena /ID# 152394
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Modena, Emilia-Romagna, Italy
Banner University of Arizona Medical Center Phoenix /ID# 151536
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Phoenix, Arizona, United States
Univ California, San Francisco /ID# 152053
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San Francisco, California, United States
Oregon Health and Science University /ID# 151690
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Portland, Oregon, United States
Vanderbilt University Medical Center /ID# 154547
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Nashville, Tennessee, United States
University of Utah /ID# 151858
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Salt Lake City, Utah, United States
Ray Dolby Brain Health Center /ID# 154965
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San Francisco, California, United States
Ucsd /Id# 152467
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La Jolla, California, United States
Mayo Clinic /ID# 151236
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Jacksonville, Florida, United States
Synexus Clinical Research US, Inc /ID# 151633
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The Villages, Florida, United States
Southern IL Univ School of Med /ID# 151769
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Springfield, Illinois, United States
Johns Hopkins Bayview Med Cnt /ID# 151893
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Baltimore, Maryland, United States
University of Kentucky Chandler Medical Center /ID# 152753
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Lexington, Kentucky, United States
North Shore University Hospital /ID# 151632
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New Hyde Park, New York, United States
Scott Research Inc. /ID# 151880
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Laurelton, New York, United States
Rhode Island Hospital /ID# 151538
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Providence, Rhode Island, United States
Keystone Clinical Studies LLC /ID# 202305
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Plymouth Meeting, Pennsylvania, United States
Houston Methodist Hospital /ID# 154810
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Houston, Texas, United States
Integrated Neurology Services /ID# 154863
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Alexandria, Virginia, United States
The Kinghorn Cancer Centre /ID# 152632
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Darlinghurst, New South Wales, Australia
Griffith University /ID# 152635
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Southport, Queensland, Australia
Parkwood Institute /ID# 164204
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London, Ontario, Canada
Rigshospitalet /ID# 153192
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Copenhagen Ø, Hovedstaden, Denmark
Policlinico Agostino Gemelli /ID# 152396
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Rome, Lazio, Italy
ASST Grande Ospedale Metropolitano Niguarda /ID# 152391
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Milano, Italy
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico /ID# 152401
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Milan, Italy
CGM Research Trust /ID# 152827
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Burwood, New Zealand
Fundacion CITA Alzheimer Fundazioa /ID# 152645
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Donostia, Pais Vasco, Spain
Fundacio ACE /ID# 152643
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Barcelona, Spain
Hospital Clinic de Barcelona /ID# 152646
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Barcelona, Spain
Karolinska University Hospital Huddinge /ID# 156705
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Stockholm, Stockholms Lan, Sweden
Sahlgrenska University Hospital Molndal /ID# 154465
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Molndal, Vastra Gotalands Lan, Sweden
Hospital Clinico Universitario San Carlos /ID# 153703
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Madrid, Spain
Hospital Universitario 12 de Octubre /ID# 152647
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Madrid, Spain
Synexus Clinical Research US, Inc. /ID# 147804
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Orlando, Florida, United States
University of South Florida /ID# 151890
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Tampa, Florida, United States