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

NCT02880956 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: M15-5662016-001634-10
• Study Type: interventional
• Target: 453
• Locations: 11 countries
• Sites: 68

Brief Summary

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

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

Outcome Measures

Primary Outcomes (2)

• Change From Baseline Over Time in CDR-SB Score

  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.

  Baseline, Week 24, Week 48, Week 72, Week 96

• Number of Participants With Treatment Emergent Adverse Events (TEAEs)

  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.

  From first dose of study drug up to last dose of study drug plus 20 weeks (up to Week 112)

Secondary Outcomes (45)

• 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.

• 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.

• 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.

• 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.

• 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.

Study Arms (4)

Placebo

PLACEBO COMPARATOR

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

Drug: placebo for ABBV-8E12

ABBV-8E12 300 mg

EXPERIMENTAL

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

Drug: ABBV-8E12

ABBV-8E12 1000 mg

EXPERIMENTAL

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

Drug: ABBV-8E12

ABBV-8E12 2000 mg

EXPERIMENTAL

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

Drug: ABBV-8E12

Interventions

ABBV-8E12 DRUG

ABBV-8E12 solution for IV infusion

Also known as: Tilavonemab

ABBV-8E12 1000 mg; ABBV-8E12 2000 mg; ABBV-8E12 300 mg

placebo for ABBV-8E12 DRUG

placebo solution for intravenous (IV) infusion

Placebo

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie: lead

Study Sites (68)

Banner University of Arizona Medical Center Phoenix /ID# 151536

Phoenix, Arizona, 85006, United States

Location

Banner Sun Health Res Inst /ID# 151895

Sun City, Arizona, 85351, United States

Location

Irvine Clinical Research /ID# 162331

Irvine, California, 92614, United States

Location

Ucsd /Id# 152467

La Jolla, California, 92037, United States

Location

Ray Dolby Brain Health Center /ID# 154965

San Francisco, California, 94113, United States

Location

Univ California, San Francisco /ID# 152053

San Francisco, California, 94143-2204, United States

Location

Brain Matters Research /ID# 147796

Delray Beach, Florida, 33445, United States

Location

Neuropsychiatric Research Center of Southwest Florida /ID# 162332

Fort Myers, Florida, 33912, United States

Location

Mayo Clinic /ID# 151236

Jacksonville, Florida, 32224, United States

Location

Synexus Clinical Research US, Inc. /ID# 147804

Orlando, Florida, 32806-1044, United States

Location

University of South Florida /ID# 151890

Tampa, Florida, 33612, United States

Location

Synexus Clinical Research US, Inc /ID# 151633

The Villages, Florida, 32162-7116, United States

Location

Emory Midtown Infectious Disease Clinic /ID# 151492

Atlanta, Georgia, 30322, United States

Location

Atlanta Center for Medical Research /ID# 151550

Atlanta, Georgia, 30331, United States

Location

NeuroStudies.net, LLC /ID# 152746

Decatur, Georgia, 30030, United States

Location

Great Lakes Clinical Trials /ID# 152754

Chicago, Illinois, 60640, United States

Location

Advocate Lutheran General Hospital /ID# 152052

Park Ridge, Illinois, 60068, United States

Location

Southern IL Univ School of Med /ID# 151769

Springfield, Illinois, 62702, United States

Location

Indiana University /ID# 151861

Indianapolis, Indiana, 46202, United States

Location

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

Fairway, Kansas, 66205, United States

Location

University of Kentucky Chandler Medical Center /ID# 152753

Lexington, Kentucky, 40536, United States

Location

Johns Hopkins Bayview Med Cnt /ID# 151893

Baltimore, Maryland, 21224, United States

Location

Massachusetts General Hospital /ID# 151770

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Physicians /ID# 151882

Boston, Massachusetts, 02115, United States

Location

Hattiesburg Clinic /ID# 202388

Hattiesburg, Mississippi, 39401, United States

Location

Princeton Medical Institute /ID# 152934

Princeton, New Jersey, 08540, United States

Location

Scott Research Inc. /ID# 151880

Laurelton, New York, 11413, United States

Location

North Shore University Hospital /ID# 151632

New Hyde Park, New York, 11040, United States

Location

Duke Cancer Center /ID# 147828

Durham, North Carolina, 27710-3000, United States

Location

Oregon Health and Science University /ID# 151690

Portland, Oregon, 97239, United States

Location

Keystone Clinical Studies LLC /ID# 202305

Plymouth Meeting, Pennsylvania, 19462, United States

Location

Rhode Island Hospital /ID# 151538

Providence, Rhode Island, 02903, United States

Location

Vanderbilt University Medical Center /ID# 154547

Nashville, Tennessee, 37232-0011, United States

Location

Kerwin Research Center /ID# 147815

Dallas, Texas, 75231-4316, United States

Location

Houston Methodist Hospital /ID# 154810

Houston, Texas, 77030, United States

Location

McGovern Medical School /ID# 204860

Houston, Texas, 77054, United States

Location

University of Utah /ID# 151858

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

Location

Integrated Neurology Services /ID# 154863

Alexandria, Virginia, 22310, United States

Location

The Kinghorn Cancer Centre /ID# 152632

Darlinghurst, New South Wales, 2010, Australia

Location

Griffith University /ID# 152635

Southport, Queensland, 4222, Australia

Location

Austin Health /ID# 152637

Heidelberg, Victoria, 3084, Australia

Location

The Royal Melbourne Hospital /ID# 202633

Parkville, Victoria, 3050, Australia

Location

Australian Alzheimer's Res Fou /ID# 152634

Nedlands, Western Australia, 6009, Australia

Location

Neurodegenerative Disorders Research /ID# 152826

West Perth, Western Australia, 6005, Australia

Location

UCL Saint-Luc /ID# 152847

Woluwe-Saint-Lambert, Brussels Capital, 1200, Belgium

Location

Universitair Ziekenhuis Leuven /ID# 152642

Leuven, Vlaams-Brabant, 3000, Belgium

Location

Groupe Sante CHC - Clinique du MontLegia /ID# 152846

Liège, 4000, Belgium

Location

Parkwood Institute /ID# 164204

London, Ontario, N6C 0A7, Canada

Location

Toronto Memory Program /ID# 147863

Toronto, Ontario, M3B 2S7, Canada

Location

Rigshospitalet /ID# 153192

Copenhagen Ø, Capital Region, 2100, Denmark

Location

Clinical Research Services Turku /ID# 152845

Turku, Southwest Finland, 20520, Finland

Location

Ita-Suomen Yliopisto /ID# 152959

Kuopio, 70210, Finland

Location

AOU di Modena /ID# 152394

Modena, Emilia-Romagna, 41126, Italy

Location

Policlinico Agostino Gemelli /ID# 152396

Rome, Lazio, 00168, Italy

Location

Duplicate_AOU Policlinico Umberto I /ID# 163144

Rome, Lazio, 00185, Italy

Location

Azienda Ospedaliera di Perugia /ID# 152397

Perugia, Umbria, 06129, Italy

Location

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

Brescia, 25125, Italy

Location

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico /ID# 152401

Milan, 20122, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda /ID# 152391

Milan, 20162, Italy

Location

Universitair Medisch Centrum Utrecht /ID# 163576

Utrecht, 3584 CX, Netherlands

Location

CGM Research Trust /ID# 152827

Burwood, 8083, New Zealand

Location

Fundacion CITA Alzheimer Fundazioa /ID# 152645

Donostia / San Sebastian, Basque Country, 20009, Spain

Location

Fundacio ACE /ID# 152643

Barcelona, 08028, Spain

Location

Hospital Clinic de Barcelona /ID# 152646

Barcelona, 08036, Spain

Location

Hospital Clinico Universitario San Carlos /ID# 153703

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre /ID# 152647

Madrid, 28041, Spain

Location

Karolinska University Hospital Huddinge /ID# 156705

Stockholm, Stockholm County, 171 77, Sweden

Location

Sahlgrenska University Hospital Molndal /ID# 154465

Mölndal, Västra Götaland County, 431 80, Sweden

Location

Related Publications (1)

• Wang D, Florian H, Lynch SY, Robieson W, Zhuang R, Kusiak C, Ross JL, Walsh JR, Graff O. Using AI-generated digital twins to boost clinical trial efficiency in Alzheimer's disease. Alzheimers Dement (N Y). 2025 Nov 22;11(4):e70181. doi: 10.1002/trc2.70181. eCollection 2025 Oct-Dec.

  PMID: 41281734 DERIVED

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction; Pick Disease of the Brain; Dementia; Tauopathies; Neurodegenerative Diseases; Memory Disorders; Nervous System Diseases

Interventions

tilavonemab

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders; Frontotemporal Dementia; Frontotemporal Lobar Degeneration; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie

abbvieclinicaltrials@abbvie.com

800-633-9110

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: August 24, 2016
• First Posted: August 26, 2016
• Study Start: January 26, 2017
• Primary Completion: March 30, 2021
• Study Completion: July 28, 2021
• Last Updated: August 26, 2022
• Results First Posted: August 26, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, 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.

Locations

BE (3); DK (1); NL (1); ES (5); US (38); NZ (1); IT (7); SE (2); AU (6); CA (2); FI (2)