A Phase IIa Multi-Center Study of 18F-FDG PET, Safety, and Tolerability of AZD0530 in Mild Alzheimer's Disease

July 25, 2019 updated by: Stephen M. Strittmatter, Yale University
AZD0530 is an inhibitor of Src and Abl family kinases1. It has been developed as treatment for malignancies because these kinases play a role in tumor invasion and proliferation. However, the Src family kinases (SFKs) are highly expressed in brain and have major effects on synaptic plasticity2. Moreover, the investigators have recently shown that a specific SFK, namely Fyn, is aberrantly activated by specific conformations of the Amyloid Beta (Aß) peptide from Alzheimer's disease (AD). Genetic deletion of Fyn rescues AD deficits in preclinical models. This clinical trial will test the potential benefit of AZD0530 for Alzheimer's disease modification.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
159

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V6T 1Z3
        • University of British Columbia, Clinic for AD & Related Disorders
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85013
        • Barrow Neurological Institute
      • Sun City, Arizona, United States, 85351
        • Banner Sun Health Research Institute
    • California
      • Los Angeles, California, United States, 90095
        • University of California, Los Angeles
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Yale Alzheimer's Disease Research Unit
    • District of Columbia
      • Washington, District of Columbia, United States, 20057
        • Georgetown University
    • Florida
      • Miami Beach, Florida, United States, 33140
        • Wien Center for Clinical Research/Mount Sinai Medical Center
      • Tampa, Florida, United States, 33613
        • University of South Florida - Health Byrd Alzheimer Institute
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa
    • Kentucky
      • Lexington, Kentucky, United States, 40504
        • University of Kentucky
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital
    • Michigan
      • Ann Arbor, Michigan, United States, 48105-2945
        • University of Michigan, Ann Arbor
    • New York
      • New York, New York, United States, 10029
        • Mount Sinai School of Medicine
      • Rochester, New York, United States, 14620
        • University of Rochester Medical Center
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Health Sciences
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health & Science University
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh, Alzheimer's Disease Research Center
    • South Carolina
      • Charleston, South Carolina, United States, 29401
        • Roper St. Francis Hospital
    • Washington
      • Seattle, Washington, United States, 98108
        • University of Washington

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

55 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

  1. NIA-Alzheimer's Association core clinical criteria for probable AD
  2. 18F-Florbetapir scan with evidence of elevated Aβ (based on central review)
  3. Age between 55-85 (inclusive)
  4. MMSE score between 18 and 26 (inclusive)

  5. Stability of permitted medications for 4 weeks. In particular:

    • Stable doses of antidepressants lacking significant anticholinergic side effects (if they are not currently depressed and do not have a history of major depression within the past 1 year)
    • Cholinesterase inhibitors and memantine are allowable if stable for 12 weeks prior to screen
  6. Geriatric Depression Scale less than 6 [Note: a score ≥6 on this screening scale may be permissible, if the subject is examined by a site clinician and judged not to be depressed.]
  7. Study partner is available who has frequent contact with the subject (e.g., average of 10 hours per week or more), and can accompany the subject to most visits to answer questions about the subject
  8. Visual and auditory acuity adequate for neuropsychological testing
  9. Good general health with no disease expected to interfere with the study
  10. Subject is not pregnant, lactating, or of childbearing potential (i.e., women must be two years post-menopausal or surgically sterile)
  11. Modified Hachinski less than or equal to 4
  12. Completed six grades of education or has a good work history
  13. Must speak English or Spanish fluently

Exclusion Criteria

  1. Any significant neurologic disease other than AD, such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities
  2. Screening/baseline MRI scan with evidence of infection, infarction, or other focal lesions or multiple lacunes or lacunes in a critical memory structure
  3. Subjects that have any contraindications for MRI studies, including claustrophobia, the presence of metal (ferromagnetic) implants, or cardiac pacemaker
  4. Major depression, bipolar disorder as described in DSM-IV within the past 1 year or psychotic features, agitation or behavioral problems within 3 months, which could lead to difficulty complying with the protocol
  5. History of schizophrenia (DSM V criteria)
  6. History of alcohol or substance abuse or dependence within the past 2 years (DSM V criteria)
  7. Clinically significant or unstable medical condition, including uncontrolled hypertension, uncontrolled diabetes, or significant cardiac, pulmonary, renal, hepatic, endocrine, or other systemic disease in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results, or the subject's ability to participate in the study.
  8. Has had a history within the last 5 years of a primary or recurrent malignant disease with the exception of non-melanoma skin cancers, resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with normal prostate-specific antigen post-treatment
  9. Clinically significant abnormalities in B12 or TFTs that might interfere with the study. A low B12 is exclusionary, unless follow-up labs (homocysteine (HC) and methylmalonic acid (MMA)) indicate that it is not physiologically significant.
  10. Residence in skilled nursing facility.
  11. Use of any excluded medication as described in study protocol
  12. Current or recent participation in any procedures involving radioactive agents, including current, past, or anticipated exposure to radiation in the workplace, such that the total radiation dose exposure to the subject in a given year would exceed the limits of annual and total dose commitment set forth in the US Code of Federal Regulations (CFR) Title 21 Section 361.1. This guideline is an effective dose of 5 rem received per year.
  13. Neutropenia defined as absolute neutrophils count of <1,800/microliter
  14. Thrombocytopenia defined as platelet count <120x103/microliter
  15. For CSF sub-study participants, a current blood clotting or bleeding disorder, or significantly abnormal PT or PTT at screening

  16. Clinically significant abnormalities in screening laboratories, including:

    • Aspartate aminotransferase (AST) >1.5 times ULN
    • Alanine aminotransferase (ALT) > 1.5 times ULN
    • Total bilirubin >1.5 times ULN
    • Serum creatinine >2.0 times ULN
  17. History of interstitial lung disease
  18. Patients whom the PI deems to be otherwise ineligible

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: AZD0530 100mg daily
Patients in the experimental group (50%) will be started on this dose. After 2 weeks, patients with a plasma drug level of <100ng/ml will receive 125mg AZD0530 daily and remain in the same experimental group as patient receiving 100mg daily.
Drug: AZD0530 100mg daily
All patients in experimental group (50%) will be started on 100mg AZD0530 daily
Other Names:
  • saracatinib
Drug: AZD0530 125mg daily
Patients with plasma drug level <100ng/ml after 2 weeks of 100mg AZD0530 daily will receive 125mg daily of AZD0530.
Other Names:
  • saracatinib
Placebo Comparator: AZD0530 Placebo
50% of patients will receive placebo treatment for the duration of the study,
Drug: Placebo
50% of patients will receive placebo treatment for the duration of the study.
Other Names:
  • saracatinib

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in Brain Glucose Uptake Measured Using 18F-FDG PET Imaging
Time Frame: 12 months
Composite measure of brain glucose uptake using F18-FDG PET in a pre-defined set of brain regions, between baseline and 12 months.
12 months
Number of Participants With One or More Serious/Other Adverse Events Subjects With Mild AD as Assessed by Analysis of Adverse Events, Including Symptoms, and Abnormal Findings on Physical and Neurological Examinations, and Standard Labs.
Time Frame: 12 months
Assessment of any adverse effects between drug and placebo-treated subjects
12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
The Effect of Treatment With AZD0530 on Cognitive and Behavioral Function
Time Frame: 12 months

The change in cognitive function between baseline and 12 months will be measured by the following tests:

  1. Alzheimer Disease Assessment Scale - Cognitive 11 (ADAS-cog11). Measures: Cognitive function Maximum score: 70; Minimum score: 0. Higher score equals worse cognitive function
  2. Mini-Mental State Examination (MMSE) Measures: Cognitive Function Maximum score: 30; Minimum score: 0. Higher score equal better cognitive function
  3. Alzheimer Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL) Measures: Ability to perform routine daily activities Maximum score: 78; Minimum score: 0. Higher score equals better ability to perform activities of daily living
  4. Clinical Dementia Rating Sum of Boxes (CDR-SO) Measures: Dementia severity Maximum score: 18; Minimum score: 0. Higher score equals more severe dementia.
12 months
Percent Change in Brain Volume Before and After Treatment
Time Frame: 12 months
Change in volume of pre-defined brain regions between baseline and 12 months of treatment.
12 months
Cerebrospinal Fluid Levels of Total Tau, Phospho-tau (p-Tau), and Amyloid-beta 1-42 (Abeta 1-42)
Time Frame: 12 months
Measure concentration of Tau and Amyloid-beta 1-42 biomarkers in the cerebrospinal fluid between baseline and 12 months of treatment
12 months
Change in Brain Glucose Uptake Measured Using 18F-FDG PET Imaging
Time Frame: 12 months
The results from the primary outcome with brain FDG-PET imaging was analyzed by ApoE genotype. Composite measure of brain glucose uptake using F18-FDG PET in a pre-defined set of brain regions, between baseline and 12 months.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Yale University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Alzheimer's Therapeutic Research Institute

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Christopher H van Dyck, MD, Yale University
  • Study Director: Paul Aisen, MD, PhD, USC Alzheimer's Therapeutic Research Institute (ATRI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 27, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 27, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 12, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 16, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 19, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 14, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 25, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1404013830
  • 4UH3TR000967-02 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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