check_circleStudy Completed

Alzheimer Disease, Amyloid beta-Protein

Phase II study of Florbetaben (BAY 94-9172) PET imaging for detection/exclusion of cerebral β-amyloid in patients with probable Alzheimer’s disease compared to healthy volunteers

Trial purpose

The aim of this study is to evaluate the efficacy, safety of a single dose of BAY 94-9172 (ZK 6013443) as an investigational medicinal product (IMP) in detecting cerebral protein-plaque (amyloid beta) with positron emission tomography (PET). IMP binds to amyloidal beta protein accumulating in brain tissue already from early stages of Alzheimer's disease (AD). IMP is therefore a potential tracer to be used for visually assessing and diagnosing Alzheimer's disease.For each subject it is required to visit the study centre during the screening phase, on the PET imaging day and for 1 follow-up visit on the next day. A telephone call for safety follow-up will be performed 7 days after IMP administration. During the screening phase the subject's medical, neurological and surgical history, specific laboratory tests related to AD, MRI of the brain and certain neuro-psychiatric tests will be performed. Clinical safety measures (physical examinations, vital signs, electrocardiogram (ECG) and laboratory tests) will be performed on the PET imaging day before IMP injection and monitored during and after two PET imaging sessions. Clinical safety measures will be performed again on the follow-up visit next day.The results of PET imaging with IMP will be compared between probable AD patients and healthy volunteers.The clinical diagnosis is based on international validated and accepted criteria and established after comprehensive clinical and neuro-psychiatric examinations

Key Participants Requirements

Sex

Both

Age

55 Years
  • - Each subject / Healthy volunteer (HV) who meets the following criteria will be eligible for enrollment into the study:
     -- Is a man or woman and is > 55 of age, whereby females must be without childbearing potential (confirmed by either: age >/= 60; or history of hysterectomy, or last spontaneous bleeding at least 2 years prior to the study start)
     -- Has at least 6 years of education
     -- Is able to provide informed consent, understand the information provided on the purpose and conduct of the trial and to comply with study procedures
     -- Possesses a general health that permits adequate compliance with all study procedures
     -- The subject, or the subject and caregiver (for probable AD patients) will be compliant and have a high probability of completing the study
     -- Informed consent has been signed and dated (with time) by the subject and/or the subject's caregiver (for probable AD patients)
    - Inclusion criteria for HV only:
     -- Has no evidence of cognitive impairment
     -- Has MRI brain scan that has been judged as "normal" (age- appropriate)
    - Inclusion criteria for patients with AD only:
     -- Presents with positive assessment for dementia of Alzheimer's type
     -- Does not fulfill the criteria DLB or VaD
     -- MRI brain scan findings that do not reveal changes indicative of stroke and/or generalized cerebrovascular disease
     -- Has a caregiver that is willing and able to attend all study visits and perform the psychometric tests requiring the presence of a caregiver
  • - Has any contraindication to MRI examination scan
    - Is scheduled for surgery and/or another invasive procedure within the time period of up to 24 hours following IMP application
    - Is allergic to the IMP or any of its constituents and/or has a history of severe allergic reactions to drugs or allergens (e.g. patients / volunteers with allergic asthma)
    - is critically ill and/or medically unstable and whose clinical course during the observation period is unpredictable
    - Has a history of exposure to any radiation >15 mSv/year (e.g. occupational or radiation therapy)
    - Is receiving drug therapy or other treatment that is known to lead to greatly fluctuating values of the hematological or chemical laboratory parameters or to severe side effects (e.g. chemotherapy)
    - Has been previously enrolled in this study or participated in a clinical study involving an investigational pharmaceutical product within 30 days prior to screening, and/or any radiopharmaceutical
    - Has a brain tumor or other intracranial lesion, a disturbance of CSF circulation (e.g., normal pressure hydrocephalus) and/or a history of head trauma or brain surgery
    - Has an inflammatory or infectious CNS disease, e.g. multiple sclerosis, HIV, syphilis, or Creutzfeldt-Jacob disease
    - Has a history, physical, laboratory or imaging findings indicative of a neurological or psychiatric illness
    - Has another disease that can cause disturbance of brain function (e.g. vitamin B12 or folic acid deficiency, disturbed thyroid function)
    - Has a history of alcohol or drug abuse
    - Has history of severe persistent depression

Trial summary

Enrollment Goal
422
Trial Dates
August 2008 - November 2010
Phase
Phase 2
Could I Receive a placebo
No
Products
NEURACEQ (Florbetaben F-18, BAY94-9172)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
Medizinische Fakultät Carl Gustav CarusDresden, 01307, Germany
Completed
Universität Erlangen-NürnbergErlangen, 91054, Germany
Completed
Universitätsklinikum EssenEssen, 45122, Germany
Completed
Universitätsklinikum MünsterMünster, 48149, Germany
Completed
Forschungszentrum Jülich GmbHJülich, 52425, Germany
Completed
Columbia UniversityNew York, 10032, United States
Completed
Institute for Neurodegenerative DisordersNew Haven, 06510, United States
Completed
New York University School of MedicineNew York, 10016, United States
Completed
Montefiore Medical CenterBronx, 10461, United States
Completed
Butler HospitalProvidence, 02906, United States
Completed
Nippon Medical School HospitalBunkyo-ku, 113-8603, Japan
Completed
Austin and Repatriation CentreHeidelberg, 3084, Australia
Completed
Westmead HospitalWestmead, 2145, Australia
Completed
Universitätsspital ZürichZürich, 8091, Switzerland
Completed
Universitätsklinikum Leipzig AöRLeipzig, 04103, Germany
Completed
Klinikum rechts der IsarMünchen, 81675, Germany
Completed
Klinikum Innenstadt der Ludwigs-Maximilians-UniversitätMünchen, 81377, Germany
Completed
HELIOS Klinikum Berlin - BuchBerlin, 13125, Germany
Completed
Yale University School of MedicineNew Haven, 06510, United States
Completed
Banner Sun Health Research InstituteSun City, 85351, United States
Completed
Stanford Hospital & ClinicsStanford, 94305, United States
Completed
Kobe University HospitalKobe, 650-0017, Japan
Completed
Institute of Biomedical Research and InnovationKobe, 650-0047, Japan
Completed
Royal Adelaide HospitalAdelaide, 5000, Australia

Primary Outcome

  • To determine the sensitivity and specificity of the independent visual assessment of detecting/excluding cerebral amyloid beta
    date_rangeTime Frame:
    Two separate scanning periods will be performed after IMP injection
    enhanced_encryption
    Safety Issue:
    no
  • To determine the sensitivity and specificity of the independent visual assessment of detecting/excluding cerebral amyloid beta. The clinical diagnosis in Part B will be established by an independent consensus panel (CP)of experts in dementia
    date_rangeTime Frame:
    Two separate scanning periods will be performed after IMP injection
    enhanced_encryption
    Safety Issue:
    no

Secondary Outcome

  • To determine the usefulness of two additional imaging windows for the visual assessment
    date_rangeTime Frame:
    Two separate scanning periods will be performed after IMP injection
    enhanced_encryption
    Safety Issue:
    no
  • To evaluate the proposed visual assessment procedure and subsequent classification
    date_rangeTime Frame:
    Two separate scanning periods will be performed after study product injection
    enhanced_encryption
    Safety Issue:
    no
  • To assess various quantitative PET image analysis methods
    date_rangeTime Frame:
    Two separate scanning periods will be performed after study product injection 7 days
    enhanced_encryption
    Safety Issue:
    no
  • To evaluate the safety and tolerability
    date_rangeTime Frame:
    Two seperate scanning periods will be performed after IMP injection
    enhanced_encryption
    Safety Issue:
    yes
  • To determine the sensitivity specificity of both, volume of interest (VOI) and voxol based quantitative image analysis in detecting/excluding cerebral beta-amyloid when compared to the independent CP diagnosis as the standard of truth
    date_rangeTime Frame:
    7 days
    enhanced_encryption
    Safety Issue:
    no
  • To confirm the safety profile of a single dose of BAY94-9172(ZK6013443) in patients with probable AD and HVs
    date_rangeTime Frame:
    7 days
    enhanced_encryption
    Safety Issue:
    yes

Trial design

An open-label, non-randomized, multi-center study to optimize image assessment and evaluate the efficacy and safety of BAY 94-9172 (ZK 6013443) positron emission tomography (PET) for detection/exclusion of cerebral amyloid beta in patients with probable Alzheimer178s disease compared to healthy volunteers
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Diagnostic
Allocation
Non-randomized
Blinding
Open Label
Assignment
Single Group Assignment
Trial Arms
1