SAD/MAD Study to Assess Safety, Tolerability, PK & PD of MEDI1814 in Subjects With Mild-Moderate Alzheimer's Disease.

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety, drug levels and effects on the body of 1 or 3 injections of MEDI1814, in people with mild to moderate Alzhiemer's Disease or healthy elderly people.

Official Title
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A Randomised, Double-Blind, Placebo Controlled, Single and Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MEDI1814 in Subjects With Mild to Moderate Alzheimer's Disease.

Conditions
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Mild-Moderate Alzheimer's Disease, Healthy Elderly

Intervention / Treatment
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* Biological: MEDI1814 for IV injection
* Biological: MEDI1814 for Subcutaneous Injection
* Biological: IV Placebo
* Biological: Placebo for Subcutaneous Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Male and female (non child bearing potential) subjects Mild-moderate Alzheimer's Disease Exclusion Criteria History or evidence of significant autoimmune disease Presence of psychiatric disorder which would affect completion of the study Current serious or unstable clinically important illness

Ages Eligible for Study
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Minimum Age: 55 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MEDI1814 IV<br>Upto 10 cohorts of subjects are planned to be dosed by IV injection, with single and multiple ascending doses ranging from 25-1800mg. | Biological: MEDI1814 for IV injection<br>* Monoclonal antibody for IV Injection<br>|
| Placebo Comparator: IV Placebo<br>Upto 10 cohorts of subjects are planned to be dosed by IV injection, with single and multiple ascending doses ranging from 25-1800mg. | Biological: MEDI1814 for IV injection<br>* Monoclonal antibody for IV Injection<br>Biological: IV Placebo<br>* Placebo for IV injection<br>|
| Experimental: MEDI1814 Sub Cutaneous Injection<br>2 cohorts of subjects are planned to be dosed by sub cutaneous injection, one single ascending dose and one multiple ascending dose cohort | Biological: MEDI1814 for Subcutaneous Injection<br>* Monoclonal antibody for subcutaneous injection<br>|
| Placebo Comparator: Subcutaneous Placebo<br>2 cohorts of subjects are planned to be dosed by sub cutaneous injection, one single ascending dose and one multiple ascending dose cohort | Biological: Placebo for Subcutaneous Injection<br>* Subcutaneous Placebo Injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerability as Measured by Participant Withdrawal for an Adverse Event | Tolerability measured by participant withdrawal for an adverse event from randomization through end of study | 4 months SAD; 7 months MAD | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration Time Curve (AUC) Time 0 to t (28 Days After 1st Dose SAD and MAD and After 3rd Dose in MAD, Day 57) | Area Under the Concentration time curve (AUC) time 0 to t; calculated from Just prior to dose administration start to 28th day after dose (pre infusion, during infusion, 1,2,4,8,24,48 hr 7, 14, 21, and 28 day) | 1 month | 
| Maximum Plasma Concentration (Cmax) of Medi1814 | Maximum plasma concentration (Cmax) of Medi1814 during 28 day period after dose administration start (prior to dosing, during infusion, 1, 2, 4, 8, 24, 48 hr, 7, 14,21, and 28 days) | 1 month | 
| Mean Termination Half Life (t 1/2) of Medi1814 | Mean termination half life (t 1/2) of Medi1814 during 28 day period after dose administration start (SAD Day 1 dose, MAD 3rd dose) | 1 month | 
| Biomarkers: Amyloid-beta in Cerebral Spinal Fluid (Two Amyloid Bets Peptides of 40 and 42 Amino Acids Were Assessed) | Biomarkers: Amyloid-beta in cerebral spinal fluid, mean percent change from baseline | Day 29 in SAD; Day 85 in MAD | 
| Biomarker: Total Amyloid-beta 1-42 in Plasma | Biomarker: Total Amyloid-beta 1-42 in plasma, mean percent change from baseline | Day 29 in SAD; Day 85 in MAD | 
| Medi1814 Concentration in CSF Samples | Medi1814 concentration in CSF Samples; number of sampled subjects with a value above the lower limit of quantification | SAD Day 29; MAD Day 85 | 
| Immunogenicity: Anti-drug Antibody Titer | Immunogenicity: Anti-drug antibody titer, subject counted if titer 50 or greater on any test, else 0 if all <50 | 4 months SAD (6 tests over 4 months; week 1, 2, 4, 8, 12, 16); 7 months MAD (7 monthly tests) |