An open-label, non-randomized study to evaluate the efficacy and safety of BAY 94-9172 (ZK 6013443) positron emission tomography (PET) imaging for detection/exclusion of cerebral [BETA]-amyloid when compared to postmortem histopathology

Summary

This trial will recruit approximately 250 subjects at 10-20 sites in the United States and other countries. This site plans to enroll 20 subjects. Subjects will have a low (e.g. non-demented subjects [NDS]) or high likelihood of beta-amyloid deposition in the brain. A total of 200 evaluable subjects are est to be required to obtain 30 histopathological specimens within the time frame of approx 1.5 years. To account for possible withdrawals and/or non-evaluable subjects, a total of 250 subjects may be necessary to be recruited into the trial. The initial period of the study, pivotal for first submission to the regulatory agencies will end after 30 valid histological specimens are available.

The study consists of a Screening Visit and a PET Imaging Visit using the tracer BAY 94-9172. A Safety Follow-up visit will follow 1 day later and amp; study staff will contact the subject 7 days later to asked about about the subjects state of health.

Subjects other than young normal healthy controls will be asked to return yearly for repeat MRI and BAY 94-9172 PET scans up to three years. A Safety Follow-up visit will follow 1 day later and study staff will contact the subject 7 days later to asked about about the subjects state of health. A follow-up period of 3 yrs after study initiation is expected to be appropriate to assess the course of [BETA]-amyloid deposition in the brain over time, gather addtnl outcome data for the evaluation of the clinical usefulness, and respect the patients[Right Quote] willingness to contribute to future scientific insights in neurodegenerative disease. The study will be collecting postmortem material and will remain open until all enrolled subjects at this site have had autopsy or until the sponsor closes the study.

This site will not be enrolling the 10 YOUNG healthy volunteers.

The efficacy analysis is based on both regional, composite [Double Quote]whole brain[Double Quote] regional, and subject level assessments of the BAY 94-9172 PET scans.

(1) The regional assessment refers to the visual evaluation of 6 pre-specified regions within the PET scan that are to be compared to the histological findings of the respective regions in the postmortem specimens.
(2) The composite [Double Quote]whole brain[Double Quote] regional assessment, which provides the secondary endpoints, will be determined from the 6 pre-specified regions as given below:
- the highest score across the six pre-defined brain regions in the PET scan will determine the composite [Double Quote]whole brain[Double Quote] regional result. That is if one region is scored and amp;quot;yes and amp;quot; for [BETA]- amyloid uptake this will be the and amp;quot;composite score and amp;quot;. The scan will be negative for tracer uptake only if none of the regions are scored and amp;quot;yes and amp;quot;.
- the and amp;apos;highest and amp;apos; score from the Consensus Panel histopathological evaluation of the 6 pre-defined brain regions will determine the composite [Double Quote]whole brain[Double Quote] regional histology result for this subject: If in any of the 6 regions [BETA]-amyloid plaques were evaluated as being and amp;apos;present and amp;apos; at a
clinico-pathologically relevant level; (either modest or frequent), the subject is determined as having clinico-pathologically relevant [BETA]-amyloid deposition in the brain. If in none of the regions the histopathological findings were assessed as being more than and amp;apos;no and amp;apos; or and amp;apos;sparse and amp;apos; [BETA]-amyloid plaques, the subject is scored as and amp;apos;no [BETA]-amyloid present and amp;apos;.

- It may occur that the CP histopathological evaluation of some regions is not possible. A subject will be included in this analysis if a CP diagnosis is available for at least 5 regions. Subjects where for only 4 or less regions a CP diagnosis is available will be excluded from this
analysis.

For the composite [Double Quote]whole brain[Double Quote] PET assessment, the composite [Double Quote]whole brain[Double Quote] histopathology is the standard of reference.

(3) The subject level analysis refers to the comparison of the overall PET scan findings (eg, either a positive or negative scan for neocortical tracer uptake, either on a visual or quantitative basis).

Participant Eligibility

1. Is at least 21 years of age (this site not enrolling the YOUNG healthy volunteers in this age group);
2. Males and Females with no child-bearing potential or negative urine pregnancy test on day of BAY 94-9172 injection.
3. Exhibits visual, auditory, and communicative capabilities adequate to provide informed
consent or assent and comply with study procedures.
4. Is willing and able to lie down in MRI and PET scanners.
5. Is willing to donate their brain for postmortem examination in case of death, except for young healthy volunteers.
6. The subject, or the subject and his/hers legally acceptable representative (eg, for probable AD and DLB patients), will be compliant and have a high probability of completing the study in the
opinion of the investigator.
7. Has been fully informed about the study, including provisions of the Health Insurance
Portability and Accountability Act (HIPAA), as applicable, and informed consent or assent
has been signed and dated (with time) by the subject and/or the subject[Single Quote]s legally acceptable
representative (eg, for probable AD and DLB patients).
8. The subject who has participated in a previous florbetaben study eg, Study 311741,
may be included in the present study. The MRI- and florbetaben PET scan do not need to be
repeated if both scans were performed within twelve months prior to inclusion.