ELND005 in Patients With Mild to Moderate Alzheimer's Disease

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

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).

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: Placebo Control; Drug: ELND005; Drug: ELND005; Drug: ELND005

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 353
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T5G 0B7
      • Glenrose Rehabilitation Hospital
  • British Columbia
    • Vancouver, British Columbia, Canada, V6T 2B5
      • University of British Columbia Hospital, Division of Neurology
  • Ontario
    • Kingston, Ontario, Canada, K7L 5G2
      • Hotel Dieu Hospital
    • London, Ontario, Canada, N6C 5J1
      • Parkwood Hospital
    • London, Ontario, Canada, N6A 4V2
      • Saint Joseph's Health Care London, Saint Joseph's Hospital, Dept. of Cognitive Neurology
    • Ottawa, Ontario, Canada, K1N 5C8
      • Sisters of Charity of Ottawa Health Service
    • Peterborough, Ontario, Canada, K9H 2P4
      • Kawartha Regional Memory Clinic
    • Toronto, Ontario, Canada, M3B 2S7
      • Toronto Memory Program
    • Toronto, Ontario, Canada, M5T 2S8
      • Whitby Mental Health Memory Clinic
    • Toronto, Ontario, Canada, M6M 3Z5
      • Gerontion Research, Inc.
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2J2
      • Neuro-Rive-Sud Memory Clinic
    • Montreal, Quebec, Canada, H1T 2M4
      • Recherche Clinique de Neurologie (Hospital Maisonneuve Rosemont)
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner Alzheimer's Institute
    • Sun City, Arizona, United States, 85351
      • Sun Health Research Institute
    • Tucson, Arizona, United States, 85724
      • University of Arizona, Health Sciences Center, Dept. of Neurology
  • California
    • Fresno, California, United States, 93720
      • Margolin Brain Institute
    • Garden Grove, California, United States, 92845
      • Collaborative Neuroscience Network, Inc.
    • Los Angeles, California, United States, 90095
      • UCLA Alzheimer's Disease Center, Dept. of Neurology
    • Orange, California, United States, 92868
      • UC Irvine Medical Center
    • San Francisco, California, United States, 94143
      • UCSF Medical Center, Dept. of Neurology
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University School of Medicine, Alzheimer's Disease Research Unit
  • District of Columbia
    • Washington, District of Columbia, United States, 20057
      • Georgetown University Medical Center, Dept. of Neurology
  • Florida
    • Delray Beach, Florida, United States, 33445
      • Brain Matters Research, Inc.
    • Hollywood, Florida, United States, 33021
      • Sunrise Clinical Research, Inc
    • Miami, Florida, United States, 33137
      • Miami Jewish Home and Hospital for the Aged
    • Miami, Florida, United States, 33173
      • Avision Research Associates, LLC
    • Orlando, Florida, United States, 32806
      • Compass Research, LLC
    • Sarasota, Florida, United States, 34243
      • Roskamp Institute
    • Sunrise, Florida, United States, 33351
      • Neurology Clinical Research, Inc.
    • Tampa, Florida, United States, 33617
      • University of South Florida Suncoast Alzheimer's and Gerontology Center
    • West Palm Beach, Florida, United States, 33407
      • Premiere Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Emory University, Dept. of Neurology
    • Decatur, Georgia, United States, 30033
      • Dekalb Neurology Associates, LLC
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Department of Neurology - Indiana University Medical Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center, Department of Neurology
  • Kentucky
    • Paducah, Kentucky, United States, 42003
      • Innovative Clinical Concepts
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital, Dept. of Neurology
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan, Taubman Health Care Center, Dept. of Neurology
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • University of Nevada School of Medicine
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Comprehensive Clinical Research
    • Eatontown, New Jersey, United States, 07724
      • The Memory Enhancement Center of America, Inc.
    • Princeton, New Jersey, United States, 08540
      • Global Medical Institutes
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Albuquerque Neuroscience, Inc.
  • New York
    • Albany, New York, United States, 12205
      • Upstate Clinical Research, LLC
    • Albany, New York, United States, 12208
      • Neurological Associates of Albany, PC
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
    • New York, New York, United States, 10032
      • Columbia University Sergievsky Center
    • Rochester, New York, United States, 14620
      • AD-CARE, Monroe Community Hospital
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • Raleigh Neurology Associates
  • Ohio
    • Toledo, Ohio, United States, 43623
      • Neurology & Neuroscience Center Of Ohio
  • Oregon
    • Medford, Oregon, United States, 97504
      • Medford Neurological and Spine Clinic
    • Portland, Oregon, United States, 97210
      • Summit Research Newtwork, Inc.
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Neurological Associates, Inc.
    • Jenkintown, Pennsylvania, United States, 19046
      • The Clinical Trial Center, LLC
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Alzheimer Disease Research Clinic
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Butler Hospital, Memory and Aging Center
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Alliance for Neuro Research, LLC dba Absher Neurology, PA
  • Texas
    • San Antonio, Texas, United States, 78229
      • Radiant Research San Antonio
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah, Dept. of Neurology
  • Vermont
    • Bennington, Vermont, United States, 05201
      • Clinical Neuroscience Research Associates, Inc-The Memory Clinic
    • Burlington, Vermont, United States, 05405
      • University of Vermont Medical Center, Fletcher Allen Health Care, Dept. of Neurology
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: OPKO Health, Inc.

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: December 4, 2007
• First Submitted That Met QC Criteria: December 4, 2007
• First Posted (Estimate): December 6, 2007

Study Record Updates

• Last Update Posted (Actual): November 1, 2019
• Last Update Submitted That Met QC Criteria: October 17, 2019
• Last Verified: October 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; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Inositol
• Other Study ID Numbers: ELND005-AD201