An Extension Study of ABBV-8E12 in Early Alzheimer's Disease (AD)

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess the long-term safety and tolerability of ABBV-8E12 in participants with early AD.

Official Title
-----------------
An Extension Study of ABBV-8E12 in Early Alzheimer's Disease

Conditions
-----------------
Alzheimer's Disease

Intervention / Treatment
-----------------
* Drug: Tilavonemab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All subjects with early AD who complete Study M15-566 (NCT02880956), meet all inclusion criteria, and do not meet any exclusion criteria are eligible for enrollment Subject was compliant during participation in Study M15-566 (NCT02880956) Subject has an identified, reliable study partner who has frequent contact with the subject and who will provide information as to the subject's cognitive and functional abilities Exclusion Criteria: The subject has any significant change in his/her medical condition since participation in Study M15-566 (NCT02880956) that could interfere with the subject's participation in Study M15-570, could place the subject at increased risk, or could confound interpretation of study results More than 8 weeks have elapsed since the subject received his/her last dose of study drug in Study M15-566 (NCT02880956) The subject is concurrently enrolled in another interventional clinical study involving a therapeutic agent with the exception of Study M15-566 (NCT02880956)

Ages Eligible for Study
-----------------
Minimum Age: 57 Years
Maximum Age: 88 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 300 mg/1000 mg Tilavonemab<br>Participants who received 300 mg tilavonemab in Study M15-566 receive 1000 mg tilavonemab in Study M15-570 via intravenous (IV) infusion every 4 weeks for up to 5.5 years. | Drug: Tilavonemab<br>* solution for IV infusion<br>* Other names: ABBV-8E12;|
| Experimental: 1000 mg/1000 mg Tilavonemab<br>Participants who received 1000 mg tilavonemab in Study M15-566 continue on the same dose in Study M15-570 via IV infusion every 4 weeks for up to 5.5 years. | Drug: Tilavonemab<br>* solution for IV infusion<br>* Other names: ABBV-8E12;|
| Experimental: 2000 mg/2000 mg Tilavonemab<br>Participants who received 2000 mg tilavonemab in Study M15-566 continue on the same dose in Study M15-570 via IV infusion every 4 weeks for up to 5.5 years. | Drug: Tilavonemab<br>* solution for IV infusion<br>* Other names: ABBV-8E12;|
| Experimental: PBO/2000 mg Tilavonemab<br>Participants who received placebo (PBO) in Study M15-566 receive 2000 mg tilavonemab in Study M15-570 via IV infusion every 4 weeks for up to 5.5 years. | Drug: Tilavonemab<br>* solution for IV infusion<br>* Other names: ABBV-8E12;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Study Drug, and Fatal TEAEs | Treatment emergent adverse events (TEAEs) are defined as any adverse event (AE) from the time of study drug administration until 20 weeks after discontinuation of study drug. An AE is defined as any untoward medical occurrence, which does not necessarily have a causal relationship with treatment. A serious AE (SAE) is defined as any event that: results in death; is life-threatening; results in hospitalization or prolongation of hospitalization; is a congenital anomaly; results in persistent or significant disability/incapacity; is an important medical event requiring medical or surgical intervention to prevent serious outcome. Severity of AEs was categorized as mild, moderate, or severe. Relationship of the AE to the study treatment was categorized as having a reasonable possibility or no reasonable possibility. | From first dose of study drug to 20 weeks after last dose of study drug; overall median time on treatment was 279 days. | 
| Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Clinical laboratory PCS criteria were adapted from National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. | Baseline to 20 weeks after last dose of study drug; overall median time on treatment was 279 days. | 
| Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Clinical laboratory PCS criteria were adapted from NCI CTCAE version 4.03 | Baseline to 20 weeks after last dose of study drug; overall median time on treatment was 279 days. | 
| Columbia-Suicide Severity Rating Scale (C-SSRS) During Double-Blind Treatment Period | The C-SSRS is a systematically administered instrument developed to track suicidal adverse events across a treatment study. The instrument is designed to assess suicidal behavior and ideation, track and assess all suicidal events, as well as the lethality of attempts. Suicidal ideation categories include the following: wish to be dead; nonspecific active suicidal thoughts; active suicidal ideation without intent to act; active suicidal ideation with some intent to act but no plan; active suicidal ideation with plan and intent. Suicidal behavior categories include the following: actual attempt; interrupted attempt; aborted attempt; preparatory acts or behavior; suicidal behavior; completed suicide. | Baseline to 20 weeks after last dose of study drug; overall median time on treatment was 279 days. | 
| Brain Magnetic Resonance Imaging (MRI) Results: Number of Participants With Cerebral Edemas, New Microhemorrhage(s), and Severe White Matter Disease |  | Baseline to 20 weeks after last dose of study drug; overall median time on treatment was 279 days. |