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

• ClinicalTrials.gov Identifier: NCT02880956
• Recruitment Status: Completed
• First Posted: August 26, 2016
• Results First Posted: August 26, 2022
• Last Update Posted: August 26, 2022
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Alzheimer's Disease	Drug: ABBV-8E12; Drug: placebo for ABBV-8E12	Phase 2

Expanded Access : An investigational treatment associated with this study is no longer available outside the clinical trial.   More info ...

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 453 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: January 26, 2017
• Actual Primary Completion Date: March 30, 2021
• Actual Study Completion Date: July 28, 2021

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; Placebo for ABBV-8E12 every 4 weeks for 96 weeks	Drug: placebo for ABBV-8E12; placebo solution for intravenous (IV) infusion
Experimental: ABBV-8E12 300 mg; ABBV-8E12 300 mg every 4 weeks for 96 weeks	Drug: ABBV-8E12; ABBV-8E12 solution for IV infusion; Other Name: Tilavonemab
Experimental: ABBV-8E12 1000 mg; ABBV-8E12 1000 mg every 4 weeks for 96 weeks	Drug: ABBV-8E12; ABBV-8E12 solution for IV infusion; Other Name: Tilavonemab
Experimental: ABBV-8E12 2000 mg; ABBV-8E12 2000 mg every 4 weeks for 96 weeks	Drug: ABBV-8E12; ABBV-8E12 solution for IV infusion; Other Name: Tilavonemab

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline Over Time in CDR-SB Score [ Time Frame: 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.
2. Number of Participants With Treatment Emergent Adverse Events (TEAEs) [ Time Frame: 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 :

1. Maximum Observed Serum Concentration (Cmax) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses [ Time Frame: 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. ]
2. Time to Cmax (Tmax) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses [ Time Frame: 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. ]
3. Serum Concentration at the End of a Dose Interval (Ctrough) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses [ Time Frame: 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. ]
4. Half-Life (T1/2) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses [ Time Frame: 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.
5. 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 [ Time Frame: 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).
6. Cmax/Dose for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses [ Time Frame: 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. ]
7. AUC0-28/Dose for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses [ Time Frame: 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).
8. Change From Baseline Over Time in Alzheimer's Disease Assessment Scale (14-Item) Cognition Portion (ADAS-Cog-14) Total Score [ Time Frame: 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.
9. Change From Baseline Over Time in ADAS-Cog-14 Comprehension of Spoken Language Score [ Time Frame: 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.
10. Change From Baseline Over Time in ADAS-Cog-14 Constructional Praxis Score [ Time Frame: 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.
11. Change From Baseline Over Time in ADAS-Cog-14 Commands Score [ Time Frame: 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.
12. Change From Baseline Over Time in ADAS-Cog-14 Delayed Word Recall Score [ Time Frame: 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.
13. Change From Baseline Over Time in ADAS-Cog-14 Ideational Praxis Score [ Time Frame: 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.
14. Change From Baseline Over Time in ADAS-Cog-14 Maze Task Score [ Time Frame: 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.
15. Change From Baseline Over Time in ADAS-Cog-14 Number Cancellation Score [ Time Frame: 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.
16. Change From Baseline Over Time in ADAS-Cog-14 Naming Score [ Time Frame: 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.
17. Change From Baseline Over Time in ADAS-Cog-14 Orientation Score [ Time Frame: 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.
18. Change From Baseline Over Time in ADAS-Cog-14 Word Recall - Number of Words Not Recalled Score [ Time Frame: 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.
19. Change From Baseline Over Time in ADAS-Cog-14 Remember Word Recognition Instructions Score [ Time Frame: 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.
20. Change From Baseline Over Time in ADAS-Cog-14 Spoken Language Ability Score [ Time Frame: 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.
21. Change From Baseline Over Time in ADAS-Cog-14 Word Find Difficulty Spontaneous Speech Score [ Time Frame: 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.
22. Change From Baseline Over Time in ADAS-Cog-14 Word Recognition Score [ Time Frame: 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.
23. Change From Baseline Over Time in Functional Activities Questionnaire (FAQ) Score [ Time Frame: 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.
24. 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 [ Time Frame: 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.
25. Change From Baseline Over Time in ADCS-CGIC-MCI Cognition Score [ Time Frame: 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.
26. Change From Baseline Over Time in ADCS-CGIC-MCI Behavior Score [ Time Frame: 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.
27. Change From Baseline Over Time in ADCS-CGIC-MCI Functional Abilities Score [ Time Frame: 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.
28. Change From Baseline Over Time in University of California's Performance Based Skills Assessment, Brief Version (UPSA-Brief) - Total Score [ Time Frame: 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.
29. 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 [ Time Frame: 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.
30. Change From Baseline Over Time in Repeatable Battery for Assessment of Neuropsychological Status (RBANS) - Total Scale Score [ Time Frame: 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.
31. Change From Baseline Over Time in RBANS - Coding Total Score [ Time Frame: 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.
32. Change From Baseline Over Time in RBANS - Digit Span Total Score [ Time Frame: 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.
33. Change From Baseline Over Time in RBANS - Figure Copy Total Score [ Time Frame: 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.
34. Change From Baseline Over Time in RBANS - Figure Recall Total Score [ Time Frame: 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.
35. Change From Baseline Over Time in RBANS - List Recognition Total Score [ Time Frame: 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.
36. Change From Baseline Over Time in RBANS - List Learning Total Score [ Time Frame: 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.
37. Change From Baseline Over Time in RBANS - Line Orientation Total Score [ Time Frame: 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.
38. Change From Baseline Over Time in RBANS - List Recall Total Score [ Time Frame: 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.
39. Change From Baseline Over Time in RBANS - Picture Naming Total Score [ Time Frame: 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.
40. Change From Baseline Over Time in RBANS - Semantic Fluency Total Score [ Time Frame: 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.
41. Change From Baseline Over Time in RBANS - Story Memory Total Score [ Time Frame: 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.
42. Change From Baseline Over Time in RBANS - Story Recall Total Score [ Time Frame: 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.
43. Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Total Score [ Time Frame: 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.
44. Change From Baseline Over Time in Neuropsychiatry Inventory (NPI) Total Score [ Time Frame: 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.
45. Change From Baseline Over Time in Alzheimer's Disease Composite Score (ADCOMS) Score [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 55 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Arizona

Banner University of Arizona Medical Center Phoenix /ID# 151536

Phoenix, Arizona, United States, 85006

Banner Sun Health Res Inst /ID# 151895

Sun City, Arizona, United States, 85351

United States, California

Irvine Clinical Research /ID# 162331

Irvine, California, United States, 92614

Ucsd /Id# 152467

La Jolla, California, United States, 92037

Ray Dolby Brain Health Center /ID# 154965

San Francisco, California, United States, 94113

Univ California, San Francisco /ID# 152053

San Francisco, California, United States, 94143-2204

United States, Florida

Brain Matters Research /ID# 147796

Delray Beach, Florida, United States, 33445

Neuropsychiatric Research Center of Southwest Florida /ID# 162332

Fort Myers, Florida, United States, 33912

Mayo Clinic /ID# 151236

Jacksonville, Florida, United States, 32224

Synexus Clinical Research US, Inc. /ID# 147804

Orlando, Florida, United States, 32806-1044

University of South Florida /ID# 151890

Tampa, Florida, United States, 33612

Synexus Clinical Research US, Inc /ID# 151633

The Villages, Florida, United States, 32162-7116

United States, Georgia

Emory Midtown Infectious Disease Clinic /ID# 151492

Atlanta, Georgia, United States, 30322

Atlanta Center for Medical Research /ID# 151550

Atlanta, Georgia, United States, 30331

NeuroStudies.net, LLC /ID# 152746

Decatur, Georgia, United States, 30030

United States, Illinois

Great Lakes Clinical Trials /ID# 152754

Chicago, Illinois, United States, 60640

Advocate Lutheran General Hospital /ID# 152052

Park Ridge, Illinois, United States, 60068

Southern IL Univ School of Med /ID# 151769

Springfield, Illinois, United States, 62702

United States, Indiana

Indiana University /ID# 151861

Indianapolis, Indiana, United States, 46202

United States, Kansas

University of Kansas Medical Center - Alzheimer's Disease Center /ID# 151554

Fairway, Kansas, United States, 66205

United States, Kentucky

University of Kentucky Chandler Medical Center /ID# 152753

Lexington, Kentucky, United States, 40536

United States, Maryland

Johns Hopkins Bayview Med Cnt /ID# 151893

Baltimore, Maryland, United States, 21224

United States, Massachusetts

Massachusetts General Hospital /ID# 151770

Boston, Massachusetts, United States, 02114

Brigham and Women's Physicians /ID# 151882

Boston, Massachusetts, United States, 02115

United States, Mississippi

Hattiesburg Clinic /ID# 202388

Hattiesburg, Mississippi, United States, 39401

United States, New Jersey

Princeton Medical Institute /ID# 152934

Princeton, New Jersey, United States, 08540

United States, New York

Scott Research Inc. /ID# 151880

Laurelton, New York, United States, 11413

North Shore University Hospital /ID# 151632

New Hyde Park, New York, United States, 11040

United States, North Carolina

Duke Cancer Center /ID# 147828

Durham, North Carolina, United States, 27710-3000

United States, Oregon

Oregon Health and Science University /ID# 151690

Portland, Oregon, United States, 97239

United States, Pennsylvania

Keystone Clinical Studies LLC /ID# 202305

Plymouth Meeting, Pennsylvania, United States, 19462

United States, Rhode Island

Rhode Island Hospital /ID# 151538

Providence, Rhode Island, United States, 02903

United States, Tennessee

Vanderbilt University Medical Center /ID# 154547

Nashville, Tennessee, United States, 37232-0011

United States, Texas

Kerwin Research Center /ID# 147815

Dallas, Texas, United States, 75231-4316

Houston Methodist Hospital /ID# 154810

Houston, Texas, United States, 77030

McGovern Medical School /ID# 204860

Houston, Texas, United States, 77054

United States, Utah

University of Utah /ID# 151858

Salt Lake City, Utah, United States, 84112-5500

United States, Virginia

Integrated Neurology Services /ID# 154863

Alexandria, Virginia, United States, 22310

Australia, New South Wales

The Kinghorn Cancer Centre /ID# 152632

Darlinghurst, New South Wales, Australia, 2010

Australia, Queensland

Griffith University /ID# 152635

Southport, Queensland, Australia, 4222

Australia, Victoria

Austin Health /ID# 152637

Heidelberg, Victoria, Australia, 3084

The Royal Melbourne Hospital /ID# 202633

Parkville, Victoria, Australia, 3050

Australia, Western Australia

Australian Alzheimer's Res Fou /ID# 152634

Nedlands, Western Australia, Australia, 6009

Neurodegenerative Disorders Research /ID# 152826

West Perth, Western Australia, Australia, 6005

Belgium

UCL Saint-Luc /ID# 152847

Woluwe-Saint-Lambert, Bruxelles-Capitale, Belgium, 1200

Universitair Ziekenhuis Leuven /ID# 152642

Leuven, Vlaams-Brabant, Belgium, 3000

Groupe Sante CHC - Clinique du MontLegia /ID# 152846

Liege, Belgium, 4000

Canada, Ontario

Parkwood Institute /ID# 164204

London, Ontario, Canada, N6C 0A7

Toronto Memory Program /ID# 147863

Toronto, Ontario, Canada, M3B 2S7

Denmark

Rigshospitalet /ID# 153192

Copenhagen Ø, Hovedstaden, Denmark, 2100

Finland

Clinical Research Services Turku /ID# 152845

Turku, Varsinais-Suomi, Finland, 20520

Ita-Suomen Yliopisto /ID# 152959

Kuopio, Finland, 70210

Italy

AOU di Modena /ID# 152394

Modena, Emilia-Romagna, Italy, 41126

Policlinico Agostino Gemelli /ID# 152396

Rome, Lazio, Italy, 00168

Duplicate_AOU Policlinico Umberto I /ID# 163144

Rome, Lazio, Italy, 00185

Azienda Ospedaliera di Perugia /ID# 152397

Perugia, Umbria, Italy, 06129

IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli /ID# 152395

Brescia, Italy, 25125

ASST Grande Ospedale Metropolitano Niguarda /ID# 152391

Milano, Italy, 20162

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico /ID# 152401

Milan, Italy, 20122

Netherlands

Universitair Medisch Centrum Utrecht /ID# 163576

Utrecht, Netherlands, 3584 CX

New Zealand

CGM Research Trust /ID# 152827

Burwood, New Zealand, 8083

Spain

Fundacion CITA Alzheimer Fundazioa /ID# 152645

Donostia, Pais Vasco, Spain, 20009

Fundacio ACE /ID# 152643

Barcelona, Spain, 08028

Hospital Clinic de Barcelona /ID# 152646

Barcelona, Spain, 08036

Hospital Clinico Universitario San Carlos /ID# 153703

Madrid, Spain, 28040

Hospital Universitario 12 de Octubre /ID# 152647

Madrid, Spain, 28041

Sweden

Karolinska University Hospital Huddinge /ID# 156705

Stockholm, Stockholms Lan, Sweden, 171 77

Sahlgrenska University Hospital Molndal /ID# 154465

Molndal, Vastra Gotalands Lan, Sweden, 431 80

Sponsors and Collaborators

AbbVie

Investigators

• Study Director: ABBVIE INC.; AbbVie

  Study Documents (Full-Text)

Documents provided by AbbVie:

Study Protocol  [PDF] October 2, 2020

Statistical Analysis Plan  [PDF] May 19, 2020

More Information

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT02880956
• Other Study ID Numbers: M15-566; 2016-001634-10 ( EudraCT Number )
• First Posted: August 26, 2016
• Results First Posted: August 26, 2022
• Last Update Posted: August 26, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)
• Time Frame: For details on when studies are available for sharing, please refer to the link below.
• Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Use Agreement (DUA). For more information on the process, or to submit a request, visit the following link.
• URL: https://vivli.org/ourmember/abbvie/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by AbbVie:

Early Alzheimer's Disease (AD); Mild Cognitive Impairment (MCI); Mild Alzheimer's Disease (AD); Tau; Early dementia; Tauopathies; AD; Neurodegenerative diseases; Memory loss; Nervous system diseases

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Tilavonemab; Nootropic Agents