Study to Evaluate the Safety and Tolerability of a New Drug Named Lu AF20513 in Patients With Mild Alzheimer's Disease

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine if multiple immunizations with Lu AF20513 is tolerable and safe in patients with mild Alzheimer's disease.

Official Title
-----------------
Interventional, Open-label, Multiple-immunization Extension Study on the Safety, Tolerability and Immunogenicity of Lu AF20513/Adjuvant in Patients With Alzheimer's Disease

Conditions
-----------------
Alzheimer Disease

Intervention / Treatment
-----------------
* Drug: Lu AF20513, low dose
* Drug: Lu AF20513, medium dose
* Drug: Lu AF20513, high dose
* Drug: Lu AF20513, double high dose


Participation Criteria
=================
Eligibility Criteria
-----------------
Main Inclusion Criteria: The patient has a diagnosis of probable Alzheimer's Disease (AD) consistent with the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria The patient has a pattern of antibodies in cerebrospinal fluid (CSF) consistent with an amyloid plaque load The patient is a man or a woman, and between ≥60 and ≤85 years of age The patient has an MRI (performed within 3 months before screening) with results consistent with the diagnosis of probable AD The patient has a mild severity of dementia The patient has a knowledgeable and reliable caregiver who will be available and able to: accompany the patient to all clinical visits, monitor IRE after each immunization, and participate with the patient at all phone visits during the study AD Patients must have completed Part A before being eligible for continued immunisations in Part B Main Exclusion Criteria: The patient has evidence of mixed etiology of dementia (i.e. absence of other neurodegenerative, neuroinflammatory or cerebrovascular disease, or another neurological, mental or systemic disease or condition likely contributing to cognitive decline) The patient has clinical and radiological findings that fulfil the standards of the National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherché et l'Enseignement en Neurosciences (NINDS-AIREN) criteria for vascular dementia The patient has a Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-5-TR) Axis I disorder other than AD; including amnestic disorders, delirium, schizophrenia or schizoaffective disorder, bipolar disorder, current major depressive episode, psychosis, panic, post-traumatic stress disorder and/or cognitive disorder not otherwise specified, (note: patients may be included if treated with a stable dose of antidepressants for at least 2 months and not fulfilling DSM-5-TR criteria for depression at Screening) The patient's eligibility MRI scan (1.5T) shows findings that correspond to more than 4 brain micro haemorrhages The patient has extensive white matter lesions as shown on the screening MRI scan (1.5T) Other protocol-defined inclusion and exclusion criteria do apply

Ages Eligible for Study
-----------------
Minimum Age: 60 Years
Maximum Age: 85 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lu AF20513, low dose (Cohort 1)<br>10 Patients with mild Alzheimer's. | Drug: Lu AF20513, low dose<br> <br> |
| Experimental: Lu AF20513, medium dose (Cohort 2)<br>10 Patients with mild Alzheimer's. | Drug: Lu AF20513, medium dose<br> <br> |
| Experimental: Lu AF20513, high dose (Cohort 3)<br>15 Patients with mild Alzheimer's. | Drug: Lu AF20513, high dose<br> <br> |
| Experimental: Lu AF20513, double high dose (Cohort 4)<br>15 Patients with mild Alzheimer's. | Drug: Lu AF20513, double high dose<br> <br> |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability assessed by composite outcome measure consisting of absolute values and changes from baseline in: adverse events, clinical safety laboratory tests, vital signs | ECGs, physical and neurological examination, suicidality assessment, Immunisation-Related Events (IRE) (selected from Brighton Collaboration guidelines) and magnetic resonance imaging (MRI) safety scans | Baseline to week 96 | 
| Antibody titre |  | Baseline to week 96 |