ELND005 in Patients With Mild to Moderate Alzheimer's Disease

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the dose-related safety and efficacy of multiple oral dosages of ELND005 as treatment for Alzheimer's disease (AD).

Detailed Description
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ELND005 (formerly known as AZD-103), scyllo-inositol, is being investigated as an orally administered treatment for AD. ELND005 may prevent or inhibit the build up of amyloid protein in the brains of AD patients. This is a randomized, double-blind, placebo-controlled, dose-ranging, safety and efficacy study of oral ELND005 in male and female participants aged 50-85 years with mild to moderate AD. Approximately 340 patients will be enrolled into the study at approximately 65 study sites. Patients will be randomized to receive either ELND005 or placebo. Each patient's participation will last approximately 18 months.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Safety and Efficacy Study of Oral ELND005 (AZD-103) in Alzheimer's Disease

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: Placebo Control
* Drug: ELND005
* Drug: ELND005
* Drug: ELND005


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of probable AD Age 50 to 85 years, inclusive Mini-Mental Status Exam (MMSE) score of 16-26, inclusive Brain magnetic resonance imaging (MRI) scan consistent with the diagnosis of AD Fluency in English, French, or Spanish Stable doses of medications (cholinesterase inhibitors and memantine allowed) Caregiver is able to attend all study visits Exclusion Criteria: Significant neurological disease other than AD Major psychiatric disorder Significant medical illness History of stroke or seizure History of a heart attack within the last 2 years Prior treatment with certain experimental medicines Presence of pacemakers or foreign metal objects in the eyes, skin, or body that would prevent patient from having MRI scan

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br> | Drug: Placebo Control<br>* ELND005 matched placebo capsules for oral administration, bid for 78 weeks<br>* Other names: scyllo-inositol;|
| Active Comparator: 2<br> | Drug: ELND005<br>* ELND005 capsules for oral administration at a dose of 250 mg bid for 78 weeks<br>* Other names: scyllo-inositol;|
| Active Comparator: 3<br> | Drug: ELND005<br>* ELND005 capsules for oral administration at a dose of 1000 mg bid for 78 weeks<br>* Other names: scyllo-inositol;|
| Active Comparator: 4<br> | Drug: ELND005<br>* ELND005 capsules for oral administration at a dose of 2000 mg bid for 78 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 78 in Neuropsychological Test Battery (NTB) Z-score (Full Analysis Set; FAS) | The NTB assessment is comprised of 9 instruments that measure cognition and executive function. Three of these tests measure immediate memory, next three measure delayed memory, and remaining three assess executive function. The total score is a weighted mean of the nine tests, referred to as the Z-score. Typically, scores range from -3 and 3, with lower scores suggesting greater cognitive impairment. | Baseline and 78 weeks | 
| Additional Analysis of Primary Outcome Measure: Change From Baseline to Week 78 in Neuropsychological Test Battery (NTB) Z-score (Per Protocol Set; PPS) | The NTB assessment is comprised of 9 instruments that measure cognition and executive function. Three of these tests measure immediate memory, next three measure delayed memory, and remaining three assess executive function. The total score is a weighted mean of the nine tests, referred to as the Z-score. Typically, scores range from -3 and 3, with lower scores suggesting greater cognitive impairment. | Baseline and 78 weeks | 
| Change From Baseline to Week 78 in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) Score (Full Analysis Set; FAS) | The ADCS-ADL is a 23-item scale that measures a subject's functional abilities as assessed by the subject's caregiver. This scale ranges from 0 to 78, with lower scores suggesting greater functional impairment. | Baseline and 78 weeks | 
| Additional Analysis of Primary Outcome Measure: Change From Baseline to Week 78 in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) Score (Per Protocol Set; PPS) | The ADCS-ADL is a 23-item scale that measures a subject's functional abilities as assessed by the subject's caregiver. This scale ranges from 0 to 78, with lower scores suggesting greater functional impairment. | Baseline and 78 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Score From Baseline to Week 78 (Full Analysis Set; FAS) | The ADAS-Cog primarily measures cognitive ability. The version used in this study was comprised of 12 items with scores ranging from 0 to 75. Higher scores suggest greater cognitive impairment. | Baseline and 78 weeks | 
| Change in Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score From Baseline to Week 78 (Full Analysis Set; FAS) | The CDR-SB consists of 6 items; 3 measuring cognitive ability and 3 measuring functional ability. The score for each of the six items range from 0 to 3; hence the total score is between 0 and 18. Higher scores suggest greater cognitive impairment. | Baseline and 78 weeks | 
| Change in Neuropsychiatric Inventory (NPI) Score From Baseline to Week 78 (Full Analysis Set; FAS) | The NPI is used to obtain information on the presence of severity of neuropsychological symptoms, and was specifically designed for use in Alzheimer's disease subjects. The scale consists of 12 items with each item having outcomes from 0 to 12; hence the total score ranges from 0 to 144. Higher scores suggest greater psychiatric impairment. | Baseline and 78 weeks |