Phase 2 N=453 Randomized Quadruple-blind Treatment

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

Alzheimer's Disease

Bottom Line

View on ClinicalTrials.gov: NCT02880956 ↗

Enrolled (actual)

453

Serious AEs

18.5%

Results posted

Aug 2022

Primary outcome: Primary: Change From Baseline Over Time in CDR-SB Score — 0.60; 0.66; 0.44; 0.63 score on a scale — p=0.740

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: ABBV-8E12 (Drug); placebo for ABBV-8E12 (Drug)
Age: Adult, Older Adult · 55+ yrs
Sex: All
Sponsor: AbbVie
Primary completion: Mar 2021

Outcome Measures

Outcome	Result	p-value
PRIMARY Change From Baseline Over Time in CDR-SB Score	0.60; 0.66; 0.44; 0.63; 1.06; 1.15	0.740
PRIMARY Number of Participants With Treatment Emergent Adverse Events (TEAEs)	108; 94; 108; 104; 12; 13	—
SECONDARY Maximum Observed Serum Concentration (Cmax) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses	108; 284; 528; 168; 426; 806	—
SECONDARY Time to Cmax (Tmax) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses	3; 2.5; 2.7; 2.4; 2.5; 2.3	—
SECONDARY Serum Concentration at the End of a Dose Interval (Ctrough) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses	28.6; 75.1; 163; 56.4; 182; 320	—
SECONDARY Half-Life (T1/2) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses	22.0; 19.4; 33.2; 19.6; 24.0; 37.5	—
SECONDARY Area Under the Concentration-Time Curve From Dosing (Time 0) to Day 28 (AUC0-28) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses	2520; 6090; 14800; 4230; 13100; 30200	—
SECONDARY Cmax/Dose for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses	0.359; 0.284; 0.264; 0.561; 0.426; 0.403	—
SECONDARY AUC0-28/Dose for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses	8.40; 6.09; 7.41; 14.1; 13.1; 15.1	—
SECONDARY Change From Baseline Over Time in Alzheimer's Disease Assessment Scale (14-Item) Cognition Portion (ADAS-Cog-14) Total Score	1.82; 1.42; 0.56; 1.86; 4.50; 3.51	0.562
SECONDARY Change From Baseline Over Time in ADAS-Cog-14 Comprehension of Spoken Language Score	0.01; 0.03; 0.04; 0.08; 0.03; 0.09	0.690
SECONDARY Change From Baseline Over Time in ADAS-Cog-14 Constructional Praxis Score	0.11; 0.05; -0.02; 0.09; 0.07; 0.23	0.456
SECONDARY Change From Baseline Over Time in ADAS-Cog-14 Commands Score	0.09; 0.10; 0.09; 0.09; 0.17; 0.12	0.945
SECONDARY Change From Baseline Over Time in ADAS-Cog-14 Delayed Word Recall Score	0.11; 0.17; -0.04; -0.09; 0.41; 0.30	0.742
SECONDARY Change From Baseline Over Time in ADAS-Cog-14 Ideational Praxis Score	0.05; 0.13; 0.02; 0.18; 0.21; 0.12	0.363
SECONDARY Change From Baseline Over Time in ADAS-Cog-14 Maze Task Score	0.15; -0.04; -0.20; 0.17; 0.37; 0.07	0.291
SECONDARY Change From Baseline Over Time in ADAS-Cog-14 Number Cancellation Score	0.33; 0.33; 0.35; 0.32; 0.43; 0.42	0.976
SECONDARY Change From Baseline Over Time in ADAS-Cog-14 Naming Score	0.02; 0.08; -0.03; 0.05; 0.11; 0.09	0.325
SECONDARY Change From Baseline Over Time in ADAS-Cog-14 Orientation Score	0.08; 0.42; 0.08; 0.49; 0.63; 0.77	0.056
SECONDARY Change From Baseline Over Time in ADAS-Cog-14 Word Recall - Number of Words Not Recalled Score	0.16; 0.03; 0.16; 0.11; 0.39; 0.32	0.325
SECONDARY Change From Baseline Over Time in ADAS-Cog-14 Remember Word Recognition Instructions Score	0.03; 0.03; 0.15; -0.02; 0.27; 0.10	0.975
SECONDARY Change From Baseline Over Time in ADAS-Cog-14 Spoken Language Ability Score	0.07; 0.08; 0.06; 0.11; 0.14; 0.04	0.867
SECONDARY Change From Baseline Over Time in ADAS-Cog-14 Word Find Difficulty Spontaneous Speech Score	0.21; 0.14; 0.11; 0.23; 0.25; 0.19	0.479
SECONDARY Change From Baseline Over Time in ADAS-Cog-14 Word Recognition Score	0.53; 0.25; -0.20; -0.02; 1.35; 0.92	0.423
SECONDARY Change From Baseline Over Time in Functional Activities Questionnaire (FAQ) Score	1.63; 1.84; 1.19; 2.06; 3.37; 3.53	0.720
SECONDARY Change From Baseline Over Time in Alzheimer's Disease Cooperative Study Clinical Global Impression of Change for Mild Cognitive Impairment (ADCS-CGIC-MCI) General Condition Score	4.91; 4.86; 4.80; 4.87; 5.29; 5.28	0.651
SECONDARY Change From Baseline Over Time in ADCS-CGIC-MCI Cognition Score	4.85; 4.81; 4.83; 4.92; 5.30; 5.29	0.722
SECONDARY Change From Baseline Over Time in ADCS-CGIC-MCI Behavior Score	4.30; 4.31; 4.28; 4.33; 4.61; 4.49	0.903
SECONDARY Change From Baseline Over Time in ADCS-CGIC-MCI Functional Abilities Score	4.59; 4.58; 4.46; 4.59; 4.97; 4.95	0.931
SECONDARY Change From Baseline Over Time in University of California's Performance Based Skills Assessment, Brief Version (UPSA-Brief) - Total Score	-4.47; -6.04; -4.10; -8.96; -13.36; -12.74	0.470
SECONDARY Change From Baseline Over Time in 24-Item Alzheimer's Disease Cooperative Study/Activities of Daily Living Scale Adapted for Patients With Mild Cognitive Impairment (ADCS-MCI-ADL-24) Total Score	-3.72; -4.51; -2.91; -3.65; -9.21; -10.25	0.438
SECONDARY Change From Baseline Over Time in Repeatable Battery for Assessment of Neuropsychological Status (RBANS) - Total Scale Score	-3.52; -4.83; -5.04; -5.17; -1.85; -1.37	0.148
SECONDARY Change From Baseline Over Time in RBANS - Coding Total Score	-0.39; -1.29; -1.40; -1.40; -1.98; -1.17	0.287
SECONDARY Change From Baseline Over Time in RBANS - Digit Span Total Score	-0.48; -0.50; -0.78; -0.64; -0.75; -0.65	0.946
SECONDARY Change From Baseline Over Time in RBANS - Figure Copy Total Score	0.29; 0.03; -0.12; -0.20; 0.07; -0.60	0.520
SECONDARY Change From Baseline Over Time in RBANS - Figure Recall Total Score	-0.23; -0.65; 0.06; -0.60; -0.97; -0.70	0.261
SECONDARY Change From Baseline Over Time in RBANS - List Recognition Total Score	0.09; -0.64; -0.38; -0.79; 0.31; 0.29	0.027 sig
SECONDARY Change From Baseline Over Time in RBANS - List Learning Total Score	-0.57; -0.67; -0.98; -1.14; -1.27; -0.36	0.854
SECONDARY Change From Baseline Over Time in RBANS - Line Orientation Total Score	0.20; 0.24; -0.05; 0.03; -0.84; 0.05	0.926
SECONDARY Change From Baseline Over Time in RBANS - List Recall Total Score	0.04; -0.15; -0.01; -0.08; 0.07; 0.05	0.202
SECONDARY Change From Baseline Over Time in RBANS - Picture Naming Total Score	-0.68; -0.87; -0.85; -0.86; -0.21; -0.10	0.303
SECONDARY Change From Baseline Over Time in RBANS - Semantic Fluency Total Score	-1.47; -1.90; -1.48; -1.65; -1.03; -1.00	0.297
SECONDARY Change From Baseline Over Time in RBANS - Story Memory Total Score	-3.06; -3.13; -2.93; -2.99; -1.62; -1.07	0.861
SECONDARY Change From Baseline Over Time in RBANS - Story Recall Total Score	-0.93; -1.01; -0.93; -0.95; -0.70; -0.95	0.683
SECONDARY Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Total Score	-0.60; -0.83; -0.48; -1.56; -1.78; -1.81	0.534
SECONDARY Change From Baseline Over Time in Neuropsychiatry Inventory (NPI) Total Score	0.93; 0.96; 0.80; 1.92; -0.03; 0.84	0.966
SECONDARY Change From Baseline Over Time in Alzheimer's Disease Composite Score (ADCOMS) Score	0.05; 0.08; 0.05; 0.08; 0.13; 0.15	0.147

Summary

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

Eligibility 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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02880956). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.