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

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.

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.

Study Overview

• Status: Completed
• Conditions: Healthy Elderly; Mild-Moderate Alzheimer's Disease
• Intervention / Treatment: Biological: Placebo for Subcutaneous Injection; Biological: MEDI1814 for IV injection; Biological: IV Placebo; Biological: MEDI1814 for Subcutaneous Injection

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • Research Site
    • Long Beach, California, United States, 90806
      • Research Site
    • Panorama City, California, United States, 91402
      • Research Site
  • Florida
    • Hallandale Beach, Florida, United States, 33009
      • Research Site
    • Hialeah, Florida, United States, 33012
      • Research Site
    • Miami, Florida, United States, 33165
      • Research Site
    • Orlando, Florida, United States, 32806
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21225
      • Research Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Research Site
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MEDI1814 IV; 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; Monoclonal antibody for IV Injection
Placebo Comparator: IV Placebo; 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; Monoclonal antibody for IV Injection; Biological: IV Placebo; Placebo for IV injection
Experimental: MEDI1814 Sub Cutaneous Injection; 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; Monoclonal antibody for subcutaneous injection
Placebo Comparator: Subcutaneous Placebo; 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; Subcutaneous Placebo Injection

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Thor Ostenfeld, MD, AstraZeneca; Principal Investigator: David Han, MD, Glendale Parexel Early Phase Clinical Unit

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2014
• Primary Completion (Actual): September 15, 2016
• Study Completion (Actual): September 15, 2016

Study Registration Dates

• First Submitted: January 13, 2014
• First Submitted That Met QC Criteria: January 13, 2014
• First Posted (Estimate): January 15, 2014

Study Record Updates

• Last Update Posted (Actual): June 3, 2019
• Last Update Submitted That Met QC Criteria: February 21, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: D4750C00001