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 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. 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.

Participants will receive the same dose of ABBV-916 for 24 weeks. Participants at the end of 24 weeks will have the option of participating in the 2-year Extension Period.

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.

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.

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.

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.

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.

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.

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.

Stage A: Percentage of Participants With Antidrug Antibodies (ADA) as a Measure of Immunogenicity Following Multiple Ascending Dose of ABBV-916

Change from baseline in brain amyloid plaque deposition (amyloid centiloid value) is measured by amyloid positron emission tomography (PET) scan.

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. Plasma Aβ42/Aβ40 value consistent with increased likelihood of positive amyloid positron emission tomography (PET), unless the participant has a positive historical 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. Receiving anticoagulant therapy. Presence of any superficial siderosis.

AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.

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 and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/