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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Alzheimer's Disease (AD)

Intervention / Treatment
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* Drug: ABBV-916
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stage A: ABBV-916<br>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. | Drug: ABBV-916<br>* Intravenous administration<br>|
| Placebo Comparator: Stage A: Placebo for ABBV-916<br>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<br>* Intravenous administration<br>|
| Experimental: Stage B: ABBV-916 Dose A<br>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<br>* Intravenous administration<br>|
| Placebo Comparator: Stage B: Placebo for ABBV-916 Dose A<br>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<br>* Intravenous administration<br>|
| Experimental: Stage B: ABBV-916 Dose B<br>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<br>* Intravenous administration<br>|
| Placebo Comparator: Stage B: Placebo for ABBV-916 Dose B<br>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<br>* Intravenous administration<br>|

What is the study measuring?
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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: Clearance (CL) of ABBV-916 | Clearance (CL) 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's Disease (AD), Early Alzheimer's Disease, ABBV-916