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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02167256
Recruitment Status : Completed
First Posted : June 19, 2014
Last Update Posted : June 27, 2018
Alzheimer's Therapeutic Research Institute
Information provided by (Responsible Party):
Stephen M. Strittmatter, Yale University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Alzheimer's Disease Drug: AZD0530 100mg daily Drug: AZD0530 125mg daily Drug: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 159 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase IIa Multi-Center Study of 18F-FDG PET, Safety, and Tolerability of AZD0530 in Mild Alzheimer's Disease
Actual Study Start Date : December 2014
Actual Primary Completion Date : February 27, 2018
Actual Study Completion Date : February 27, 2018

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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

Drug: AZD0530 125mg daily
Patients with plasma drug level <100ng/ml after 2 weeks of 100mg AZD0530 daily will receive 125mg daily of AZD0530.

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.

Primary Outcome Measures :
  1. The effect of treatment with AZD0530 on 12-month reductions in 18F-FDG PET measurements of the cerebral metabolic rate for glucose (CMRgl) using statistical parametric mapping (SPM) statistical region of in [ Time Frame: 12 months ]
  2. Safety and tolerability of treatment with AZD0530 over a 12-month period in 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 ]

Secondary Outcome Measures :
  1. The effect of treatment with AZD0530 on cognitive and behavioral function in participants with mild AD. [ Time Frame: 12 months ]
    The change in cognitive deficit will be measured by ADAS-cog, MMSE, ADCS-ADL, and CDR-SO.

  2. To assess the effect of treatment with AZD0530 on the rate of brain atrophy using volumetric magnetic resonance imaging (MRI). [ Time Frame: 12 months ]
  3. To assess the effect of treatment with AZD0530 on CSF biomarkers of AD (particularly CSF total Tau and CSF pTau). [ Time Frame: 12 months ]
  4. To assess the influence of APOE genotype on the effects of treatment with AZD0530. [ Time Frame: 12 months ]
    The results from the primary outcome with FDG-PET will be segregated in this secondary analysis by ApoE genotype.

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Ages Eligible for Study:   55 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 Hackinski 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02167256

  Show 22 Study Locations
Sponsors and Collaborators
Yale University
Alzheimer's Therapeutic Research Institute
Study Director: Christopher H van Dyck, MD Yale University
Study Director: Paul Aisen, MD, PhD USC Alzheimer's Therapeutic Research Institute (ATRI)

Responsible Party: Stephen M. Strittmatter, Professor of Neurology and Neurobiology, Yale University Identifier: NCT02167256     History of Changes
Other Study ID Numbers: 1404013830
4UH3TR000967-02 ( U.S. NIH Grant/Contract )
First Posted: June 19, 2014    Key Record Dates
Last Update Posted: June 27, 2018
Last Verified: June 2018

Additional relevant MeSH terms:
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Fluorodeoxyglucose F18
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors