Clinical Trials/NCT02880956

NCT02880956

Completed

Phase 2

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

AbbVie68 sites in 5 countries453 target enrollmentJanuary 26, 2017

ConditionsAlzheimer's Disease

Interventionsplacebo for ABBV-8E12 ABBV-8E12

DrugsABBV-8E12 placebo for ABBV-8E12

Overview

Phase: Phase 2
Intervention: placebo for ABBV-8E12
Conditions: Alzheimer's Disease
Sponsor: AbbVie
Enrollment: 453
Locations: 68
Primary Endpoint: Change From Baseline Over Time in CDR-SB Score
Status: Completed
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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

Registry

clinicaltrials.gov

Start Date

January 26, 2017

End Date

July 28, 2021

Last Updated

3 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

AbbVie

Responsible Party

Sponsor

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 ≤
•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.

Arms & Interventions

Placebo

Placebo for ABBV-8E12 every 4 weeks for 96 weeks

Intervention: placebo for ABBV-8E12

ABBV-8E12 300 mg

ABBV-8E12 300 mg every 4 weeks for 96 weeks

Intervention: ABBV-8E12

ABBV-8E12 1000 mg

ABBV-8E12 1000 mg every 4 weeks for 96 weeks

Intervention: ABBV-8E12

ABBV-8E12 2000 mg

ABBV-8E12 2000 mg every 4 weeks for 96 weeks

Intervention: ABBV-8E12

Outcomes

Primary Outcomes

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.

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 Outcomes

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.)
Change From Baseline Over Time in ADAS-Cog-14 Constructional Praxis Score(Baseline, Week 24, Week 48, Week 72, Week 96)
Change From Baseline Over Time in ADAS-Cog-14 Maze Task Score(Baseline, Week 24, Week 48, Week 72, Week 96)
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)
Change From Baseline Over Time in ADAS-Cog-14 Commands Score(Baseline, Week 24, Week 48, Week 72, Week 96)
Change From Baseline Over Time in ADAS-Cog-14 Ideational Praxis Score(Baseline, Week 24, Week 48, Week 72, Week 96)
Change From Baseline Over Time in ADAS-Cog-14 Naming Score(Baseline, Week 24, Week 48, Week 72, Week 96)
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.)
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)
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.)
Change From Baseline Over Time in ADAS-Cog-14 Number Cancellation Score(Baseline, Week 24, Week 48, Week 72, Week 96)
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)
Change From Baseline Over Time in ADCS-CGIC-MCI Behavior Score(Baseline, Week 48, Week 96)
Change From Baseline Over Time in ADAS-Cog-14 Delayed Word Recall Score(Baseline, Week 24, Week 48, Week 72, Week 96)
Change From Baseline Over Time in ADAS-Cog-14 Orientation Score(Baseline, Week 24, Week 48, Week 72, Week 96)
Change From Baseline Over Time in ADAS-Cog-14 Remember Word Recognition Instructions Score(Baseline, Week 24, Week 48, Week 72, Week 96)
Change From Baseline Over Time in ADAS-Cog-14 Word Find Difficulty Spontaneous Speech Score(Baseline, Week 24, Week 48, Week 72, Week 96)
Change From Baseline Over Time in ADAS-Cog-14 Word Recognition Score(Baseline, Week 24, Week 48, Week 72, Week 96)
Change From Baseline Over Time in ADAS-Cog-14 Spoken Language Ability Score(Baseline, Week 24, Week 48, Week 72, Week 96)
Change From Baseline Over Time in Functional Activities Questionnaire (FAQ) Score(Baseline, Week 24, Week 48, Week 72, Week 96)
Change From Baseline Over Time in ADCS-CGIC-MCI Cognition Score(Baseline, Week 48, Week 96)
Change From Baseline Over Time in ADCS-CGIC-MCI Functional Abilities Score(Baseline, Week 48, Week 96)
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)
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)
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)
Change From Baseline Over Time in RBANS - Figure Copy Total Score(Baseline, Week 24, Week 48, Week 72, Week 96)
Change From Baseline Over Time in RBANS - Line Orientation Total Score(Baseline, Week 24, Week 48, Week 72, Week 96)
Change From Baseline Over Time in RBANS - Picture Naming Total Score(Baseline, Week 24, Week 48, Week 72, Week 96)
Change From Baseline Over Time in RBANS - Semantic Fluency Total Score(Baseline, Week 24, Week 48, Week 72, Week 96)
Change From Baseline Over Time in RBANS - Story Memory Total Score(Baseline, Week 24, Week 48, Week 72, Week 96)
Change From Baseline Over Time in RBANS - Story Recall Total Score(Baseline, Week 24, Week 48, Week 72, Week 96)
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)
Change From Baseline Over Time in RBANS - Coding Total Score(Baseline, Week 24, Week 48, Week 72, Week 96)
Change From Baseline Over Time in RBANS - List Learning Total Score(Baseline, Week 24, Week 48, Week 72, Week 96)
Change From Baseline Over Time in Alzheimer's Disease Composite Score (ADCOMS) Score(Baseline, Week 24, Week 48, Week 72, Week 96)
Change From Baseline Over Time in RBANS - Digit Span Total Score(Baseline, Week 24, Week 48, Week 72, Week 96)
Change From Baseline Over Time in RBANS - Figure Recall Total Score(Baseline, Week 24, Week 48, Week 72, Week 96)
Change From Baseline Over Time in RBANS - List Recognition Total Score(Baseline, Week 24, Week 48, Week 72, Week 96)
Change From Baseline Over Time in RBANS - List Recall Total Score(Baseline, Week 24, Week 48, Week 72, Week 96)
Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Total Score(Baseline, Week 24, Week 48, Week 72, Week 96)
Change From Baseline Over Time in Neuropsychiatry Inventory (NPI) Total Score(Baseline, Week 24, Week 48, Week 72, Week 96)