Clinical trial NCT02880956: A Study to Evaluate the Efficacy and Safety of ABBV-8E12 in Participants With Early Alzheimer's Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alzheimer's Disease
Keywords: 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
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2016-08-26
Enrollment: 453
Sex: ALL
Minimum age (years): 55
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Change From Baseline Over Time in CDR-SB Score
timeFrame: Baseline, Week 24, Week 48, Week 72, Week 96
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: From first dose of study drug up to last dose of study drug plus 20 weeks (up to Week 112)
Secondary outcomes:
measure: Maximum Observed Serum Concentration (Cmax) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses
timeFrame: 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.
measure: Time to Cmax (Tmax) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses
timeFrame: 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.
measure: Serum Concentration at the End of a Dose Interval (Ctrough) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses
timeFrame: 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.
measure: Half-Life (T1/2) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses
timeFrame: 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.
measure: 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
timeFrame: 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.
measure: Cmax/Dose for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses
timeFrame: 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.
measure: AUC0-28/Dose for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses
timeFrame: 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.
measure: Change From Baseline Over Time in Alzheimer's Disease Assessment Scale (14-Item) Cognition Portion (ADAS-Cog-14) Total Score
timeFrame: Baseline, Week 24, Week 48, Week 72, Week 96
measure: Change From Baseline Over Time in ADAS-Cog-14 Comprehension of Spoken Language Score
timeFrame: Baseline, Week 24, Week 48, Week 72, Week 96
measure: Change From Baseline Over Time in ADAS-Cog-14 Constructional Praxis Score
timeFrame: Baseline, Week 24, Week 48, Week 72, Week 96
measure: Change From Baseline Over Time in ADAS-Cog-14 Commands Score
timeFrame: Baseline, Week 24, Week 48, Week 72, Week 96
measure: Change From Baseline Over Time in ADAS-Cog-14 Delayed Word Recall Score
timeFrame: Baseline, Week 24, Week 48, Week 72, Week 96
measure: Change From Baseline Over Time in ADAS-Cog-14 Ideational Praxis Score
timeFrame: Baseline, Week 24, Week 48, Week 72, Week 96
measure: Change From Baseline Over Time in ADAS-Cog-14 Maze Task Score
timeFrame: Baseline, Week 24, Week 48, Week 72, Week 96
measure: Change From Baseline Over Time in ADAS-Cog-14 Number Cancellation Score
timeFrame: Baseline, Week 24, Week 48, Week 72, Week 96
measure: Change From Baseline Over Time in ADAS-Cog-14 Naming Score
timeFrame: Baseline, Week 24, Week 48, Week 72, Week 96
measure: Change From Baseline Over Time in ADAS-Cog-14 Orientation Score
timeFrame: Baseline, Week 24, Week 48, Week 72, Week 96
measure: Change From Baseline Over Time in ADAS-Cog-14 Word Recall - Number of Words Not Recalled Score
timeFrame: Baseline, Week 24, Week 48, Week 72, Week 96
measure: Change From Baseline Over Time in ADAS-Cog-14 Remember Word Recognition Instructions Score
timeFrame: Baseline, Week 24, Week 48, Week 72, Week 96
measure: Change From Baseline Over Time in ADAS-Cog-14 Spoken Language Ability Score
timeFrame: Baseline, Week 24, Week 48, Week 72, Week 96
measure: Change From Baseline Over Time in ADAS-Cog-14 Word Find Difficulty Spontaneous Speech Score
timeFrame: Baseline, Week 24, Week 48, Week 72, Week 96
measure: Change From Baseline Over Time in ADAS-Cog-14 Word Recognition Score
timeFrame: Baseline, Week 24, Week 48, Week 72, Week 96
measure: Change From Baseline Over Time in Functional Activities Questionnaire (FAQ) Score
timeFrame: Baseline, Week 24, Week 48, Week 72, Week 96
measure: 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
timeFrame: Baseline, Week 48, Week 96
measure: Change From Baseline Over Time in ADCS-CGIC-MCI Cognition Score
timeFrame: Baseline, Week 48, Week 96
measure: Change From Baseline Over Time in ADCS-CGIC-MCI Behavior Score
timeFrame: Baseline, Week 48, Week 96
measure: Change From Baseline Over Time in ADCS-CGIC-MCI Functional Abilities Score
timeFrame: Baseline, Week 48, Week 96
measure: Change From Baseline Over Time in University of California's Performance Based Skills Assessment, Brief Version (UPSA-Brief) - Total Score
timeFrame: Baseline, Week 48, Week 96
measure: 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
timeFrame: Baseline, Week 48, Week 96
measure: Change From Baseline Over Time in Repeatable Battery for Assessment of Neuropsychological Status (RBANS) - Total Scale Score
timeFrame: Baseline, Week 24, Week 48, Week 72, Week 96
measure: Change From Baseline Over Time in RBANS - Coding Total Score
timeFrame: Baseline, Week 24, Week 48, Week 72, Week 96
measure: Change From Baseline Over Time in RBANS - Digit Span Total Score
timeFrame: Baseline, Week 24, Week 48, Week 72, Week 96
measure: Change From Baseline Over Time in RBANS - Figure Copy Total Score
timeFrame: Baseline, Week 24, Week 48, Week 72, Week 96
measure: Change From Baseline Over Time in RBANS - Figure Recall Total Score
timeFrame: Baseline, Week 24, Week 48, Week 72, Week 96
measure: Change From Baseline Over Time in RBANS - List Recognition Total Score
timeFrame: Baseline, Week 24, Week 48, Week 72, Week 96
measure: Change From Baseline Over Time in RBANS - List Learning Total Score
timeFrame: Baseline, Week 24, Week 48, Week 72, Week 96
measure: Change From Baseline Over Time in RBANS - Line Orientation Total Score
timeFrame: Baseline, Week 24, Week 48, Week 72, Week 96
measure: Change From Baseline Over Time in RBANS - List Recall Total Score
timeFrame: Baseline, Week 24, Week 48, Week 72, Week 96
measure: Change From Baseline Over Time in RBANS - Picture Naming Total Score
timeFrame: Baseline, Week 24, Week 48, Week 72, Week 96
measure: Change From Baseline Over Time in RBANS - Semantic Fluency Total Score
timeFrame: Baseline, Week 24, Week 48, Week 72, Week 96
measure: Change From Baseline Over Time in RBANS - Story Memory Total Score
timeFrame: Baseline, Week 24, Week 48, Week 72, Week 96
measure: Change From Baseline Over Time in RBANS - Story Recall Total Score
timeFrame: Baseline, Week 24, Week 48, Week 72, Week 96
measure: Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Total Score
timeFrame: Baseline, Week 24, Week 48, Week 72, Week 96
measure: Change From Baseline Over Time in Neuropsychiatry Inventory (NPI) Total Score
timeFrame: Baseline, Week 24, Week 48, Week 72, Week 96
measure: Change From Baseline Over Time in Alzheimer's Disease Composite Score (ADCOMS) Score
timeFrame: Baseline, Week 24, Week 48, Week 72, Week 96
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Banner University of Arizona Medical Center Phoenix /ID# 151536
state: Arizona
city: Sun City
country: United States
facility: Banner Sun Health Res Inst /ID# 151895
state: Arizona
city: Irvine
country: United States
facility: Irvine Clinical Research /ID# 162331
state: California
city: La Jolla
country: United States
facility: Ucsd /Id# 152467
state: California
city: San Francisco
country: United States
facility: Ray Dolby Brain Health Center /ID# 154965
state: California
city: San Francisco
country: United States
facility: Univ California, San Francisco /ID# 152053
state: California
city: Delray Beach
country: United States
facility: Brain Matters Research /ID# 147796
state: Florida
city: Fort Myers
country: United States
facility: Neuropsychiatric Research Center of Southwest Florida /ID# 162332
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic /ID# 151236
state: Florida
city: Orlando
country: United States
facility: Synexus Clinical Research US, Inc. /ID# 147804
state: Florida
city: Tampa
country: United States
facility: University of South Florida /ID# 151890
state: Florida
city: The Villages
country: United States
facility: Synexus Clinical Research US, Inc /ID# 151633
state: Florida
city: Atlanta
country: United States
facility: Emory Midtown Infectious Disease Clinic /ID# 151492
state: Georgia
city: Atlanta
country: United States
facility: Atlanta Center for Medical Research /ID# 151550
state: Georgia
city: Decatur
country: United States
facility: NeuroStudies.net, LLC /ID# 152746
state: Georgia
city: Chicago
country: United States
facility: Great Lakes Clinical Trials /ID# 152754
state: Illinois
city: Park Ridge
country: United States
facility: Advocate Lutheran General Hospital /ID# 152052
state: Illinois
city: Springfield
country: United States
facility: Southern IL Univ School of Med /ID# 151769
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University /ID# 151861
state: Indiana
city: Fairway
country: United States
facility: University of Kansas Medical Center - Alzheimer's Disease Center /ID# 151554
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky Chandler Medical Center /ID# 152753
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Med Cnt /ID# 151893
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital /ID# 151770
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Physicians /ID# 151882
state: Massachusetts
city: Hattiesburg
country: United States
facility: Hattiesburg Clinic /ID# 202388
state: Mississippi
city: Princeton
country: United States
facility: Princeton Medical Institute /ID# 152934
state: New Jersey
city: Laurelton
country: United States
facility: Scott Research Inc. /ID# 151880
state: New York
city: New Hyde Park
country: United States
facility: North Shore University Hospital /ID# 151632
state: New York
city: Durham
country: United States
facility: Duke Cancer Center /ID# 147828
state: North Carolina
city: Portland
country: United States
facility: Oregon Health and Science University /ID# 151690
state: Oregon
city: Plymouth Meeting
country: United States
facility: Keystone Clinical Studies LLC /ID# 202305
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital /ID# 151538
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt University Medical Center /ID# 154547
state: Tennessee
city: Dallas
country: United States
facility: Kerwin Research Center /ID# 147815
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital /ID# 154810
state: Texas
city: Houston
country: United States
facility: McGovern Medical School /ID# 204860
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah /ID# 151858
state: Utah
city: Alexandria
country: United States
facility: Integrated Neurology Services /ID# 154863
state: Virginia
city: Darlinghurst
country: Australia
facility: The Kinghorn Cancer Centre /ID# 152632
state: New South Wales
city: Southport
country: Australia
facility: Griffith University /ID# 152635
state: Queensland
city: Heidelberg
country: Australia
facility: Austin Health /ID# 152637
state: Victoria
city: Parkville
country: Australia
facility: The Royal Melbourne Hospital /ID# 202633
state: Victoria
city: Nedlands
country: Australia
facility: Australian Alzheimer's Res Fou /ID# 152634
state: Western Australia
city: West Perth
country: Australia
facility: Neurodegenerative Disorders Research /ID# 152826
state: Western Australia
city: Woluwe-Saint-Lambert
country: Belgium
facility: UCL Saint-Luc /ID# 152847
state: Bruxelles-Capitale
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven /ID# 152642
state: Vlaams-Brabant
city: Liege
country: Belgium
facility: Groupe Sante CHC - Clinique du MontLegia /ID# 152846
city: London
country: Canada
facility: Parkwood Institute /ID# 164204
state: Ontario
city: Toronto
country: Canada
facility: Toronto Memory Program /ID# 147863
state: Ontario
city: Copenhagen Ø
country: Denmark
facility: Rigshospitalet /ID# 153192
state: Hovedstaden
city: Turku
country: Finland
facility: Clinical Research Services Turku /ID# 152845
state: Varsinais-Suomi
city: Kuopio
country: Finland
facility: Ita-Suomen Yliopisto /ID# 152959
city: Modena
country: Italy
facility: AOU di Modena /ID# 152394
state: Emilia-Romagna
city: Rome
country: Italy
facility: Policlinico Agostino Gemelli /ID# 152396
state: Lazio
city: Rome
country: Italy
facility: Duplicate_AOU Policlinico Umberto I /ID# 163144
state: Lazio
city: Perugia
country: Italy
facility: Azienda Ospedaliera di Perugia /ID# 152397
state: Umbria
city: Brescia
country: Italy
facility: IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli /ID# 152395
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda /ID# 152391
city: Milan
country: Italy
facility: Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico /ID# 152401
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht /ID# 163576
city: Burwood
country: New Zealand
facility: CGM Research Trust /ID# 152827
city: Donostia
country: Spain
facility: Fundacion CITA Alzheimer Fundazioa /ID# 152645
state: Pais Vasco
city: Barcelona
country: Spain
facility: Fundacio ACE /ID# 152643
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona /ID# 152646
city: Madrid
country: Spain
facility: Hospital Clinico Universitario San Carlos /ID# 153703
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre /ID# 152647
city: Stockholm
country: Sweden
facility: Karolinska University Hospital Huddinge /ID# 156705
state: Stockholms Lan
city: Molndal
country: Sweden
facility: Sahlgrenska University Hospital Molndal /ID# 154465
state: Vastra Gotalands Lan
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: