A Study to Assess the Adverse Events, Change in Disease Activity, and How Intravenous ABBV-1758 Moves Through the Body of Adult Participants With Alzheimer's Disease

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of ABBV-1758 in Subjects With 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 is to assess the adverse events, change in disease activity, and how intravenous ABBV-1758 moves through the body of adult participants with Alzheimer's Disease

ABBV-1758 is an investigational drug being developed for the treatment of Alzheimer's disease in adults. This study is conducted in 3 stages. Stage A is a multiple ascending dose study with a 1 in 5 chance (4:1 randomization) that participants are assigned to receive placebo. Stage B is a dose expansion phase, also using 4:1 randomization for ABBV-1758 or placebo. Stage C enrolls Japanese and Chinese participants with the same randomization scheme. This may be followed by a 12-month, blinded Extension Period where participants receive ABBV-1758 or placebo based on their amyloid positron emission tomography (PET) results. Approximately 210 participants will be enrolled at about 65 sites in the United States, China, and Japan.

Participants will receive intravenous (IV) or subcutaneous (SC) doses of ABBV-1758 or placebo once every 4 weeks (Q4W) for 24 weeks and will be followed for an additional 12 weeks. Participants will have the option of participating in a 12-month, blinded Extension Period receiving ABBV-1758 or placebo based on amyloid PET results.

There may be higher treatment burden for participants in this trial compared to their standard of care due to study procedures. Participants will attend regular visits during the study at a hospital or clinic. The safety of the treatment will be checked by medical assessments, blood tests, and completing questionnaires.

Study Overview

• Status: Not yet recruiting
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: ABBV-1758; Drug: ABBV-1758; Drug: Placebo for ABBV-1758; Drug: Placebo for ABBV-1758

• Study Type: Interventional
• Enrollment (Estimated): 210
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: ABBVIE CALL CENTER; Phone Number: 844-663-3742; Email: abbvieclinicaltrials@abbvie.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants meeting all the following criteria for Alzheimer's disease (AD):
• Plasma pTau217/Aβ42 ratio that is predictive of elevated brain amyloid at Screening.
• Participants with amyloid positron emission tomography (PET) scan results consistent with significant amyloid pathology (as determined by a Centiloid value of 50 or higher).
• Participants must have a Mini-Mental State Examination (MMSE) score of 20 or higher at Screening.

Exclusion Criteria:

• Participants with screening magnetic resonance imaging (MRI) that show evidence of another potential etiology for progressive dementia.
• Participants who have any current serious conditions or illnesses that are not adequately controlled, or any conditions that, in the investigator's opinion, could interfere with the analyses in this study, including but not limited to psychiatric, neurologic (other than AD), cardiovascular, hepatic, renal, gastroenterological, respiratory, endocrinologic, immunologic, or hematologic, metabolic, pulmonary, ophthalmologic, dermatologic, and/or any history of abnormal laboratory results that are indicative of significant disease(s).
• Participants who had prior exposure to ABBV-1758 or any history of exposure to anti-amyloid beta monoclonal antibody (mAb) treatment.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

18

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stage A-ABBV-1758 Dose A; Participants will receive ABBV-1758 dose A once every 4 weeks (Q4W).	Drug: ABBV-1758; Intravenous (IV) or Subcutaneous (SC); Drug: ABBV-1758; Subcutaneous (SC)
Placebo Comparator: Stage A-Placebo for ABBV-1758 Dose A; Participants will receive Placebo dose A once every 4 weeks (Q4W).	Drug: Placebo for ABBV-1758; Intravenous (IV) or Subcutaneous (SC); Drug: Placebo for ABBV-1758; Subcutaneous (SC)
Experimental: Stage A-ABBV-1758 Dose B; Participants will receive ABBV-1758 dose B Q4W.	Drug: ABBV-1758; Intravenous (IV) or Subcutaneous (SC); Drug: ABBV-1758; Subcutaneous (SC)
Placebo Comparator: Stage A-Placebo for ABBV-1758 Dose B; Participants will receive Placebo dose B Q4W.	Drug: Placebo for ABBV-1758; Intravenous (IV) or Subcutaneous (SC); Drug: Placebo for ABBV-1758; Subcutaneous (SC)
Experimental: Stage A-ABBV-1758 Dose C; Participants will receive ABBV-1758 dose C Q4W.	Drug: ABBV-1758; Intravenous (IV) or Subcutaneous (SC); Drug: ABBV-1758; Subcutaneous (SC)
Placebo Comparator: Stage A-Placebo for ABBV-1758 Dose C; Participants will receive Placebo dose C Q4W.	Drug: Placebo for ABBV-1758; Intravenous (IV) or Subcutaneous (SC); Drug: Placebo for ABBV-1758; Subcutaneous (SC)
Experimental: Stage A-ABBV-1758 Dose D; Participants will receive ABBV-1758 dose D Q4W.	Drug: ABBV-1758; Intravenous (IV) or Subcutaneous (SC); Drug: ABBV-1758; Subcutaneous (SC)
Placebo Comparator: Stage A-Placebo for ABBV-1758 Dose D; Participants will receive Placebo dose D Q4W.	Drug: Placebo for ABBV-1758; Intravenous (IV) or Subcutaneous (SC); Drug: Placebo for ABBV-1758; Subcutaneous (SC)
Experimental: Stage B- ABBV-1758 - Expanded Cohort 1; Participants will receive ABBV-1758 dose determined in Stage A Q4W.	Drug: ABBV-1758; Intravenous (IV) or Subcutaneous (SC); Drug: ABBV-1758; Subcutaneous (SC)
Placebo Comparator: Stage B- Placebo for ABBV-1758 - Expanded Cohort 1; Participants will receive Placebo dose determined in Stage A Q4W.	Drug: Placebo for ABBV-1758; Intravenous (IV) or Subcutaneous (SC); Drug: Placebo for ABBV-1758; Subcutaneous (SC)
Experimental: Stage B- ABBV-1758- Expanded Cohort 2; Participants will receive ABBV-1758 dose determined in Stage A Q4W.	Drug: ABBV-1758; Intravenous (IV) or Subcutaneous (SC); Drug: ABBV-1758; Subcutaneous (SC)
Placebo Comparator: Stage B- Placebo for ABBV-1758- Expanded Cohort 2; Participants will receive Placebo dose determined in Stage A Q4W.	Drug: Placebo for ABBV-1758; Intravenous (IV) or Subcutaneous (SC); Drug: Placebo for ABBV-1758; Subcutaneous (SC)
Experimental: Stage C- ABBV-1758 - Japanese Cohort 1; Participants will receive ABBV-1758 dose determined in Stage A Q4W.	Drug: ABBV-1758; Intravenous (IV) or Subcutaneous (SC); Drug: ABBV-1758; Subcutaneous (SC)
Placebo Comparator: Stage C- Placebo for ABBV-1758 - Japanese Cohort 1; Participants will receive Placebo dose determined in Stage A Q4W.	Drug: Placebo for ABBV-1758; Intravenous (IV) or Subcutaneous (SC); Drug: Placebo for ABBV-1758; Subcutaneous (SC)
Experimental: Stage C- ABBV-1758- Japanese Cohort 2; Participants will receive ABBV-1758 dose determined in Stage A Q4W.	Drug: ABBV-1758; Intravenous (IV) or Subcutaneous (SC); Drug: ABBV-1758; Subcutaneous (SC)
Placebo Comparator: Stage C- Placebo for ABBV-1758- Japanese Cohort 2; Participants will receive Placebo dose determined in Stage A Q4W.	Drug: Placebo for ABBV-1758; Intravenous (IV) or Subcutaneous (SC); Drug: Placebo for ABBV-1758; Subcutaneous (SC)
Experimental: Stage C- ABBV-1758-Chinese Cohort; Participants will receive ABBV-1758 dose determined in Stage A Q4W.	Drug: ABBV-1758; Intravenous (IV) or Subcutaneous (SC); Drug: ABBV-1758; Subcutaneous (SC)
Placebo Comparator: Stage C- Placebo for ABBV-1758- Chinese Cohort; Participants will receive Placebo dose determined in Stage A Q4W.	Drug: Placebo for ABBV-1758; Intravenous (IV) or Subcutaneous (SC); Drug: Placebo for ABBV-1758; Subcutaneous (SC)

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 participant or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with the treatment. The investigator assesses the relationship of each event to the use of study drug.	Up to approximately 36 weeks
Number of Participants with Abnormal Change in Clinical Laboratory Test Results Like Hematology will be Assessed	Number of participants with abnormal change in clinical laboratory test results like hematology will be assessed.	Up to approximately 36 weeks
Change From Baseline in amyloid-related imaging abnormalities (ARIA) Measured by Magnetic Resonance Im-aging (MRI)	Magnetic resonance imaging (MRI) of several different brain regions was per-formed, and volumetric analysis was con-ducted to quantify midbrain atrophy. Negative changes in values indicate a re-duction in volume.	Up to approximately 36 weeks
Number of Participants with Abnormal Change From Baseline in Vital Sign Measurements	Number of participants with abnormal change from baseline in vital sign measurements like systolic and diastolic blood pressure will be assessed.	Up to approximately 36 weeks
Change From Baseline in Electrocardiograms (ECGs)	12-lead resting ECGs will be recorded. Parameters include heart rate, PR interval, QT interval, QRS duration, and QT interval corrected using Fridericia's formula (QTcF).	Up to approximately 36 weeks
Change from Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS)	The C-SSRS is a clinician-rated instrument that reports the severity of both suicidal ideation and behavior, with a higher score denoting more severe suicidal ideation and behavior.	Up to approximately 36 weeks
Stage A, B, and C: Change from Baseline in Brain Amyloid Plaque Deposition	Measured by amyloid positron emission tomography (PET)	Up to approximately 28 Weeks
Stage A and C: Maximum Plasma Concentration (Cmax) of ABBV-1758	Cmax of ABBV-1758	Up to approximately 12 months
Stage A and C: Time to Cmax (Tmax) of ABBV-1758	Tmax of ABBV-1758	Up to approximately 12 months
Stage A and C: Trough Concentration measured at the end of a dosing interval at steady state (Ctrough) of ABBV-1758	Ctrough of ABBV-1758	Up to approximately 12 months
Stage A and C: Area under the Plasma Concentration-time Curve from Time Zero to the End of the Dosing Interval (AUCtau) of ABBV-1758	AUCtau of ABBV-1758	Up to approximately 12 months
Stage A and C: Average Serum Concentration at Steady-State (Cav,ss) of ABBV-1758	Cav,ss of ABBV-1758	Up to approximately 12 months
Stage A and C: Accumulation ratio for (AUCtau) of ABBV-1758	AUCtau of ABBV-1758	Up to approximately 12 months
Stage A and C: Total Body Clearance (CL) of ABBV-1758	CL of ABBV-1758	Up to approximately 12 months
Stage A and C: Apparent Clearance (CL/F) of ABBV-1758	CL/F of ABBV-1758	Up to approximately 12 months
Stage A and C: Volume of Distribution at Steady-State (Vss)	Vss of ABBV-1758	Up to approximately 12 months
Stage A and C: Apparent Volume of Distribution during the Terminal Phase (Vz)	Vz of ABBV-1758	Up to approximately 12 months
Stage A and C: Terminal Phase Elimination Rate Constant (β) of ABBV-1758	β of ABBV-1758	Up to approximately 12 months
Stage A and C: Terminal Phase Elimination Half-Life (t1/2) of ABBV-1758	Terminal phase elimination half-life of ABBV-1758	Up to approximately 12 months
Stage A and C: Effective Half-Life (T1/2,eff)	T1/2,eff of ABBV-1758	Up to approximately 12 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Estimated): May 15, 2026
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): November 1, 2030

Study Registration Dates

• First Submitted: May 15, 2026
• First Submitted That Met QC Criteria: May 15, 2026
• First Posted (Actual): May 20, 2026

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 15, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Alzheimer's Disease; ABBV-1758
• 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: M25-804

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.: No