A Study to Assess Safety of ABBV-916 and How Intravenous ABBV-916 Moves Through Body and Affects Brain Amyloid Plaque Clearance in Adult Participants (Aged 50-90 Years) With Early Alzheimer's Disease

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of ABBV-916 in Subjects With Early Alzheimer's Disease

Alzheimer's disease (AD) is a progressive, irreversible neurological disorder and is the most common cause of dementia in the elderly population. Clinical symptoms of the disease may begin with occasional forgetfulness such as misplacement of items, forgetting important dates or events, and may progress to noticeable memory loss, increased confusion and agitation, and eventually, loss of independence and non-responsiveness. This study will assess how safe and effective ABBV-916 is in treating early AD. Adverse events, change in disease activity, and how ABBV-916 moves through body of participants will be assessed.

ABBV-916 is an investigational drug being developed for the treatment of early AD. This study is conducted in 2 stages. Stage A is a multiple ascending dose study. There is a 1 in 4 chance that participants are assigned to receive placebo. Stage B is a proof-of-concept study. In Stage B, there is a 1 in 5 chance that participants will be assigned to receive placebo. The first 6 months of this study are "double-blind," which means that neither the trial participant nor the study doctors know which treatments will be given. This will be followed by a 2-year extension period in which all participants will receive ABBV-916. Approximately 195 participants aged 50-90 years will be enrolled in about 90 sites across the world.

Participants will receive intravenous (IV) doses of ABBV-916 or placebo once every 4 weeks (Q4W) for 24 weeks and will be followed for an additional 16 weeks. Participants will have the option of participating in a 2-year, open-label, Extension Period receiving IV ABBV-916.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, magnetic resonance imaging (MRI), blood tests, checking for side effects and completing questionnaires.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease (AD)
• Intervention / Treatment: Drug: Placebo; Drug: ABBV-916

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85710-6152
      • Tucson Neuroscience Research /ID# 244957
  • California
    • Irvine, California, United States, 92614
      • Irvine Clinical Research /ID# 239469
    • San Diego, California, United States, 92103-2204
      • Artemis Institute for Clinical Research - San Diego /ID# 244508
    • San Diego, California, United States, 92103
      • Pacific Research Network, Inc. /ID# 244083
    • Santa Ana, California, United States, 92705
      • Syrentis Clinical Research /ID# 239682
  • Florida
    • Aventura, Florida, United States, 33180
      • Aventura Neurological Associates /ID# 243892
    • Lady Lake, Florida, United States, 32162
      • Charter Research - Lady Lake /ID# 244657
    • Lake Worth, Florida, United States, 33462-1141
      • JEM Research Institute /ID# 239122
    • Maitland, Florida, United States, 32751
      • ClinCloud - Maitland /ID# 244507
    • Melbourne, Florida, United States, 32940-8288
      • ClinCloud LLC - Viera/Melbourne /ID# 240635
    • Merritt Island, Florida, United States, 32952-3616
      • Merritt Island Medical Research /ID# 239495
    • Miami, Florida, United States, 33125-4013
      • Optimus U /ID# 245868
    • Miami, Florida, United States, 33126
      • Finlay Medical Research /ID# 245996
    • Miami, Florida, United States, 33155
      • Allied Biomedical Res Inst Inc /ID# 244823
    • Ocala, Florida, United States, 34470
      • Renstar Medical Research /ID# 240153
    • Ocoee, Florida, United States, 34761-4547
      • K2 Medical Research - Ocoee /ID# 246849
    • Orlando, Florida, United States, 32751
      • K2 Medical Research - Orlando - South Orlando Avenue /ID# 243919
    • Orlando, Florida, United States, 32803-1839
      • Charter Research - Winter Park /ID# 244778
    • Orlando, Florida, United States, 32819
      • Headlands Research - Orlando /ID# 239119
    • Ormond Beach, Florida, United States, 32174
      • Neurology Associates Ormond Beach /ID# 245527
    • Palmetto Bay, Florida, United States, 33157
      • IMIC Inc. Medical Research /ID# 245900
    • Stuart, Florida, United States, 34997-5765
      • Alzheimer's Research and Treatment Center - Stuart /ID# 245477
    • Wellington, Florida, United States, 33414
      • Alzheimer's Research and Treatment Center - Wellington /ID# 245201
    • West Palm Beach, Florida, United States, 33407-3209
      • Premiere Research Institute - Palm Beach /ID# 240108
    • Winter Park, Florida, United States, 32789-4681
      • Clinical Site Partners (CSP) - Orlando /ID# 245127
    • Winter Park, Florida, United States, 32789
      • Conquest Research /ID# 243916
  • Georgia
    • Columbus, Georgia, United States, 31909
      • Columbus Memory Center /ID# 245054
  • Michigan
    • Farmington Hills, Michigan, United States, 48334-2977
      • QUEST Research Institute /ID# 239459
  • New Jersey
    • Toms River, New Jersey, United States, 08755-5043
      • Advanced Memory Research Institute of NJ /ID# 239533
  • Pennsylvania
    • Plymouth Meeting, Pennsylvania, United States, 19462
      • Keystone Clinical Studies LLC /ID# 239973
  • Texas
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc /ID# 244917
  • Virginia
    • Fairfax, Virginia, United States, 22031-5207
      • Re:Cognition Health - Fairfax VA /ID# 239501

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of Stage 3 or Stage 4 Alzheimer's disease (AD) based on the 2018 National Institute on Aging (NIA)-Alzheimer's Association (AA) Research Framework Criteria.

  • Mini-Mental State Examination (MMSE) score of 20 to 28, inclusive, at Screening.
  • Blood-based biomarker results with a value consistent with amyloid positron emission tomography (PET) positivity. The biomarker will be chosen by the sponsor and described in the Laboratory Manual. Biomarker results will not be required for eligibility if the participant has a positive Amyloid PET scan meeting the central reader criteria.
• Amyloid PET scan results consistent with amyloid pathology.
• Stage B: Participants must have a study partner who spends a minimum average of 10 hours per week with the participant.

Exclusion Criteria:

• Significant pathological findings on brain MRI at screening including, but not limited to, evidence of vasogenic edema, 4 or more microhemorrhages, any macrohemorrhages, any superficial siderosis, or severe white matter disease.
• Any anticoagulants or have a bleeding disorder that is not adequately controlled.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Stage A: Placebo for ABBV-916; Participants will receive Placebo for 24 weeks. Participants at the end of 24 weeks will have the option of participating in the 2-year Extension Period.	Drug: Placebo; Intravenous administration
Experimental: Stage B: ABBV-916 Dose A; Participants will receive ABBV-916 Dose A for 24 weeks. Participants at the end of 24 weeks will have the option of participating in the 2-year Extension Period.	Drug: ABBV-916; Intravenous administration
Experimental: Stage B: ABBV-916 Dose B; Participants will receive ABBV-916 Dose B for 24 weeks. Participants at the end of 24 weeks will have the option of participating in the 2-year Extension Period.	Drug: ABBV-916; Intravenous administration
Experimental: Stage A: ABBV-916; Participants will receive ABBV-916 for 24 weeks. Participants at the end of 24 weeks will have the option of participating in the 2-year Extension Period.	Drug: ABBV-916; Intravenous administration
Placebo Comparator: Stage B: Placebo for ABBV-916; Participants will receive Placebo for 24 weeks. Participants at the end of 24 weeks will have the option of participating in the 2-year Extension Period.	Drug: Placebo; Intravenous administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Experiencing Adverse Events (AEs)	An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study.	Up to approximately 160 weeks
Stage A: Maximum Observed Serum Concentration (Cmax) for Multiple Ascending Dose of ABBV-916	Cmax of ABBV-916 will be determined.	Up to approximately 24 weeks
Stage A: Time to Cmax (Tmax) for Multiple Ascending Dose of ABBV-916	Tmax of ABBV-916 will be determined.	Up to approximately 24 weeks
Stage A: Apparent Terminal Phase Elimination Rate Constant (β) of ABBV-916	Apparent terminal phase elimination rate constant (β) of ABBV-916 will be determined.	Up to approximately 24 weeks
Stage A: Terminal Phase Elimination Half-Life (t1/2) of ABBV-916	T1/2 of ABBV-916 will be determined.	Up to approximately 24 weeks
Stage A: Trough Serum Concentration (Ctrough) of ABBV-916 at the End of a Dosing Interval	Ctrough of ABBV-916 will be determined.	Up to approximately 24 weeks
Stage A: Area Under the Concentration-Time Curve (AUC) of ABBV-916	AUC of ABBV-916 will be determined.	Up to approximately 24 weeks
Stage A: Cerebrospinal Fluid (CSF) Concentration as a Measure of ABBV-916 Crossing the Blood Brain Barrier	The central value for ratio of ABBV-916 concentration in cerebrospinal fluid (CSF) to that in serum will be estimated for evaluation of the fraction of ABBV-916 crossing the blood brain barrier.	Up to approximately 24 weeks
Stage A: Percentage of Participants With Antidrug Antibodies (ADA) as a Measure of Immunogenicity Following Multiple Ascending Dose of ABBV-916	Antidrug antibody (ADA) classification and titers for positive ADA samples will be determined.	Up to approximately 24 weeks
Stage B: Change in Brain Amyloid Plaque Deposition (Amyloid Centiloid Value)	Change from baseline in brain amyloid plaque deposition (amyloid centiloid value) is measured by amyloid positron emission tomography (PET) scan.	Baseline (Week 0) through Week 24

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2022
• Primary Completion (Actual): November 19, 2025
• Study Completion (Actual): November 19, 2025

Study Registration Dates

• First Submitted: March 21, 2022
• First Submitted That Met QC Criteria: March 21, 2022
• First Posted (Actual): March 22, 2022

Study Record Updates

• Last Update Posted (Actual): December 10, 2025
• Last Update Submitted That Met QC Criteria: December 4, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Alzheimer's Disease (AD); Early Alzheimer's Disease; ABBV-916
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease
• Other Study ID Numbers: M22-721; 2022-500691-59-00 (Other Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information.
• IPD Sharing Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• IPD Sharing Access Criteria: To learn more about the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• 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.: Yes