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 beta-amyloid in patients with probable Alzheimer’s disease compared to healthy volunteers - Safety and efficacy of positron emission tomography imaging with BAY 94-9172 (ZK 6013443)

• Register: EUCTR
• Last refreshed on: 22 October 2012
• Main ID: EUCTR2007-002256-42-DE
• Date of registration: 25/04/2008
• Prospective Registration: Yes
• Primary sponsor: Bayer Schering Pharma AG
• Public title: 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 beta-amyloid in patients with probable Alzheimer’s disease compared to healthy volunteers - Safety and efficacy of positron emission tomography imaging with BAY 94-9172 (ZK 6013443)
• Scientific title: 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 beta-amyloid in patients with probable Alzheimer’s disease compared to healthy volunteers - Safety and efficacy of positron emission tomography imaging with BAY 94-9172 (ZK 6013443)
• Date of first enrolment: 24/06/2009
• Target sample size: 438
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-002256-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: compared to Healthy Volunteers (HV)

Countries of recruitment

Germany

Key inclusion & exclusion criteria

Inclusion criteria:
Inclusion criteria for all study participants
Each AD patient / HV who meets the following criteria will be eligible for enrollment into the study:
1.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 surgical sterilization or of hysterectomy, or last spontaneous bleeding at least 2 years prior to the study start)
2. has at least 6 years of education
3.is able to provide informed consent, understand the information provided on the purpose and conduct of the trial and exhibits adequate visual, auditory and communication capabilities to enable compliance with study procedures. This includes performing the psychometric testing and being able to lie down flat in the PET scanner
4.possesses a general health that permits adequate compliance with all study procedures as ascertained by a detailed review of the medical history, laboratory and physical examination findings, which must be performed within 8 weeks ( up to 12 weeks is acceptable) prior to administration of IMP
5.the subject, or the subject and caregiver (for probable AD patients) will be compliant and have a high probability of completing the study in the opinion of the investigator
6.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
Each HV who meets the following criteria will be eligible for enrollment into the study:
1.Has no evidence of cognitive impairment as indicated by a clinical dementia rating (CDR, [Hughes et al. 1993]) score of 0 (zero) and a score of = 28 in the Mini-Mental Status Examination (MMSE, [Folstein et al. 1975])
2.has in the CERAD neuropsychological test battery [Welsh et al. 1994] a z- score of
= (-1.00) for each subtest (except for the MMSE which is covered by criterion 1 above)
3.has MRI brain scan that has been judged as “normal (age- appropriate)” including ARWMC scale [Wahlund et al. 2001] scores supporting the lack of cerebrovascular disease (e.g., a white matter lesion score of 0 or 1 or 2 and a basal ganglia score of 0 or 1) and a Sheltens scale [Sheltens et al. 1992] verifying the lack of cerebral atrophy (e.g. bilateral temporal lobe atrophy visual score of 0 or 1)

Inclusion criteria for patients with AD only
Each patient screened for AD who meets the following criteria will be eligible for enrollment into the study:
1.presents with positive assessment for dementia of Alzheimer’s type in accordance with the DSM-IV-TR and probable AD according to the NINCDS-ADRDA criteria and fulfils none of the exclusion criteria of either (see Appendix 2 and Appendix 3)
2.does not fulfill the ICC criteria for probable DLB (Appendix 4), the NINDS-AIREN for probable VaD (Appendix 6) or the Neary [Neary et al. 1998] criteria for FTD (Appendix 5)
3.has a MMSE score of ? 18 and = 26
4.has a CDR [Hughes et al. 1993] score of 0.5, 1 or 2
5.MRI brain scan findings that do not reveal changes indicative of stroke and/or generalized cerebrovascular disease (e.g., the ARWMC scale) changes limited to: a white matter lesion score of 0 or 1 or 2 and a basal ganglia score of 0 or 1)
6.has a caregiver who is willing and able to attend all study visits and perform the psychometric tests requiring the presence of a caregiver

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range

Exclusion criteria:
Exclusion criteria for all study participants
Each AD patient / HV who meets any of the following criteria must not participate in this study:
1.has any contraindication to MRI examination, e.g. metal implants or phobia as determined by the onsite radiologist performing the scan
2.is scheduled for surgery and/or another invasive procedure within the time period of up to 24 hours following IMP application
3.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)
4.is critically ill and/or medically unstable and whose clinical course during the observation period is unpredictable, e.g. patients / volunteers within 14 days of myocardial infarction or stroke, unstable patients / volunteers with previous surgery (within 7 days), patients with advanced heart insufficiency (NYHA stage IV), or with acute renal failure
5.has a history of exposure to any radiation >15 mSv/year (e.g. occupational or radiation therapy)
6.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)
7.has received any contrast material (X-ray, MRI) or radiopharmaceuticals within 48 hours prior to the application of the IMP or for whom application of such a substance is planned for the 24 hours following IMP administration
8.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 within 10 radioactive half-lives prior to IMP administration
9.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
10.has an inflammatory or infectious CNS disease, e.g. multiple sclerosis, HIV, syphilis, or Creutzfeld-Jacob disease
11.has a history, physical, laboratory or imaging findings indicative of a significant neurological or psychiatric illness
12.has another disease that can cause disturbance of brain function (e.g. vitamin B12 or folic acid deficiency, disturbed thyroid function)
13.has a history of alcohol or drug abuse
14.has history of severe persistent depression




Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Probable Alzheimer Disease patients compared to Healthy Volunteers. The clinical diagnosis - in Part A made by the investigator, in Part B established by an independent consensus panel of experts in dementia - will serve as the standard of truth and will be based on internationally accepted, validated (diagnostic) criteria and established after comprehensive review of all available clinical, neuro-psychiatric and other relevant data.
MedDRA version: 9.1 Level: LLT Classification code 10001896 Term: Alzheimer's disease

Intervention(s)

Product Name: Florbetaben (BAY 94-9172)
Product Code: ([F-18]AV1/ZK)
Pharmaceutical Form: Radiopharmaceutical precursor
Concentration unit: MBq megabecquerel(s)
Concentration type: not less then
Concentration number: 300-

Primary Outcome(s)

Main Objective: To determine the sensitivity and specificity of the independent visual assessment of BAY 94-9172 PET images (from the 90 to 110 min imaging window) in detecting/excluding cerebral amyloid beta in patients with probable AD compared to HV. The clinical diagnosis - in Part A made by the investigator, in Part B established by an independent consensus panel - based on internationally accepted, validated criteria and established after comprehensive clinical and neuro-psychiatric examination, will serve as the standard of truth.

Secondary Objective: To evaluate the usefulness of two additional imaging windows (i.e. 45 to 60 min and 110 to 130 min) for the visual assessment based on sensitivity and specificity values obtained in these two imaging windows.
To determine the sensitivity, specificity of both volume of interest (VOI) and voxel-based quantitative image analysis in detecting/excluding cerebral beta-amyloid when compared to the diagnosis as established by an independent CP as the standard of truth.
To confirm the safety profile of a single dose of BAY 94-9172 (ZK 6013443) in patients with probable AD and HVs.

Primary end point(s): The primary efficacy variables will be the sensitivity and specificity of the visual assessment of the BAY 94-9172 PET images in detecting/excluding cerebral beta-amyloid in patients with probable AD compared to HV. The 90 to 110 min imaging window and the majority read approach will be used to determine these variables.
Sensitivity will be calculated from the data obtained from patients with probable AD, while specificity will be calculated from HVs. The independent CP diagnosis will be the standard of truth for Part B.

Secondary ID(s)

311741