A Study to Assess the Safety and Effects of ABBV-1758 Following Subcutaneous or Intravenous Injections in Participants With Alzheimer's Disease

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of ABBV-1758 in Participants 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. The purpose of this study is to test how safe ABBV-1758 is, how well it works, how the body processes it and what effects it has on the body.

ABBV-1758 is an investigational drug being developed for the treatment of Alzheimer's disease. 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. Approximately 210 participants will be enrolled at about 55 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 additional 12 weeks in the Follow-up Period. 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: 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

Study Locations

• United States
  • California
    • Irvine, California, United States, 92614
      • Recruiting
      • Irvine Center for Clinical Research /ID# 277752
  • Colorado
    • Boulder, Colorado, United States, 80301
      • Recruiting
      • Alpine Clinical Research Center - Boulder - 47th Street /ID# 277856
  • Florida
    • Bradenton, Florida, United States, 34207
      • Recruiting
      • Key Clinical Research LLC /ID# 277800
      • Contact: Site Coordinator; Phone Number: 941-241-5539
    • Clermont, Florida, United States, 34711
      • Recruiting
      • K2 Medical Research - Clermont /ID# 277859
    • Lady Lake, Florida, United States, 32159
      • Recruiting
      • K2 Medical Research - The Villages /ID# 278290
    • Stuart, Florida, United States, 34997
      • Recruiting
      • Alzheimer'S Research And Treatment Center - Stuart /ID# 278206
    • Wellington, Florida, United States, 33414
      • Recruiting
      • Alzheimer's Research And Treatment Center - Wellington /ID# 277749
      • Contact: Site Coordinator; Phone Number: (561) 209-2400
    • Winter Park, Florida, United States, 32789
      • Recruiting
      • Conquest Research - Winter Park /ID# 277760
      • Contact: Site Coordinator; Phone Number: 407-916-0060
  • Massachusetts
    • Watertown, Massachusetts, United States, 02472
      • Recruiting
      • Adams Clinical /ID# 277754
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Recruiting
      • Neurology Clinic - Cordova /ID# 277790
  • Texas
    • Dallas, Texas, United States, 75231
      • Recruiting
      • Kerwin Medical Center /ID# 277788
      • Contact: Site Coordinator; Phone Number: 972-433-9100

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):

  • In regions where timely testing is feasible (e.g., results available within 4 weeks of Visit 1), plasma biomarker that is predictive of elevated brain amyloid at Screening for participants that do not have known elevated brain amyloid based on previous amyloid positron emission tomography (PET) results.
  • 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.

• Participants with other significant pathological findings on brain MRI at screening, including but not limited to:

  • Evidence of vasogenic edema
  • 4 or more microhemorrhages (defined as 10 mm or less at the greatest diameter)
  • Any macrohemorrhage (defined as greater than 10 mm at the greatest diameter)
  • Any superficial siderosis
  • Severe white matter disease

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)
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)
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)
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)
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)
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)
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)
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)
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: Placebo for ABBV-1758 Dose A; Participants will receive Placebo for ABBV-1758.	Drug: Placebo for ABBV-1758; Intravenous (IV) or Subcutaneous (SC); Drug: Placebo for ABBV-1758; Subcutaneous (SC)
Placebo Comparator: Placebo for ABBV-1758 Dose B; Participants will receive Placebo for ABBV-1758.	Drug: Placebo for ABBV-1758; Intravenous (IV) or Subcutaneous (SC); Drug: Placebo for ABBV-1758; Subcutaneous (SC)
Placebo Comparator: Placebo for ABBV-1758 Dose C; Participants will receive Placebo for ABBV-1758.	Drug: Placebo for ABBV-1758; Intravenous (IV) or Subcutaneous (SC); Drug: Placebo for ABBV-1758; Subcutaneous (SC)
Placebo Comparator: Placebo for ABBV-1758 Dose D; Participants will receive Placebo for ABBV-1758.	Drug: Placebo for ABBV-1758; Intravenous (IV) or Subcutaneous (SC); Drug: Placebo for ABBV-1758; Subcutaneous (SC)
Placebo Comparator: Placebo for ABBV-1758 - Expanded Cohort 1; Participants will receive Placebo for ABBV-1758.	Drug: Placebo for ABBV-1758; Intravenous (IV) or Subcutaneous (SC); Drug: Placebo for ABBV-1758; Subcutaneous (SC)
Placebo Comparator: Placebo for ABBV-1758- Expanded Cohort 2; Participants will receive Placebo for ABBV-1758.	Drug: Placebo for ABBV-1758; Intravenous (IV) or Subcutaneous (SC); Drug: Placebo for ABBV-1758; Subcutaneous (SC)
Placebo Comparator: Placebo for ABBV-1758 - Japanese Cohort 1; Participants will receive Placebo for ABBV-1758.	Drug: Placebo for ABBV-1758; Intravenous (IV) or Subcutaneous (SC); Drug: Placebo for ABBV-1758; Subcutaneous (SC)
Placebo Comparator: Placebo for ABBV-1758- Japanese Cohort 2; Participants will receive Placebo for ABBV-1758.	Drug: Placebo for ABBV-1758; Intravenous (IV) or Subcutaneous (SC); Drug: Placebo for ABBV-1758; Subcutaneous (SC)
Placebo Comparator: Placebo for ABBV-1758- Chinese Cohort; Participants will receive Placebo for ABBV-1758.	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
Percentage 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 40 weeks
Percentage of Participants with Abnormal Change from Baseline in Clinical Laboratory Test Results	Number of participants with abnormal change in clinical laboratory test results like hematology will be assessed.	Up to approximately 40 weeks
Percentage of Participants With Amyloid-Related Imaging Abnormalities (ARIA)	Amyloid related imaging abnormalities represent a spectrum of magnetic resonance imaging findings primarily observed in participants undergoing treatment with anti-amyloid therapies.	Up to approximately 40 weeks
Percentage 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 40 weeks
Percentage of Participants with Abnormal Change From Baseline in Electrocardiograms (ECGs) Parameters	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 40 weeks
Percentage of Participants Experiencing Any Suicidal Ideation or Suicidal Behavior As Assessed by 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 40 weeks
Stage A, B, and C: Change from Baseline in Brain Amyloid Load	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 40 weeks
Stage A and C: Time to Cmax (Tmax) of ABBV-1758	Tmax of ABBV-1758	Up to approximately 40 weeks
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 40 weeks
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 40 weeks
Stage A and C: Average Serum Concentration at Steady-State (Cav,ss) of ABBV-1758	Cav,ss of ABBV-1758	Up to approximately 40 weeks
Stage A and C: Accumulation ratio for (AUCtau) of ABBV-1758	AUCtau of ABBV-1758	Up to approximately 40 weeks
Stage A and C: Total Body Clearance (CL) of ABBV-1758	CL of ABBV-1758	Up to approximately 40 weeks
Stage A and C: Apparent Clearance (CL/F) of ABBV-1758	CL/F of ABBV-1758	Up to approximately 40 weeks
Stage A and C: Volume of Distribution at Steady-State (Vss)	Vss of ABBV-1758	Up to approximately 40 weeks
Stage A and C: Apparent Volume of Distribution during the Terminal Phase (Vz)	Vz of ABBV-1758	Up to approximately 40 weeks
Stage A and C: Terminal Phase Elimination Rate Constant (β) of ABBV-1758	β of ABBV-1758	Up to approximately 40 weeks
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 40 weeks
Stage A and C: Effective Half-Life (T1/2,eff)	T1/2,eff of ABBV-1758	Up to approximately 40 weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2026
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): October 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): June 23, 2026
• Last Update Submitted That Met QC Criteria: June 18, 2026
• Last Verified: June 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