Impact of FBB PET Amyloid Imaging in Change of Diagnosis in Patients With AD

Study Overview
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Brief Summary
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This phase 4 study will explore, in the context of the present French clinical practice, the impact of florbetaben 18F (FBB) in patients evaluated for AD who require a biomarker for etiologic determination of the cognitive and functional impairment, but in whom: lumbar puncture was not feasible for medical conditions results of cerebrospinal fluid (CSF) analysis were considered ambiguous by treating physicians lumbar puncture (LP) was refused by the patient

Detailed Description
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It will be conducted in an outpatient setting at the tertiary memory clinics (CMRR) in France in patients with a preliminary diagnosis based on the completion of a prior, full diagnostic workup, not more than 12 months previously - which could include, but will not be limited to brain imaging if needed (magnetic resonance imaging (MRI) or computed tomography (CT)), neuropsychological evaluation including a Mini-Mental Status Examination (MMSE), CSF examination and other examinations according to Haute Autorité de santé (HAS, National Authority of Health, France) Recommendations - and in whom: lumbar puncture was not feasible for medical conditions results of cerebrospinal fluid (CSF) analysis were considered ambiguous by treating physicians lumbar puncture (LP) was refused by the patient For all subjects the study will comprise 3 outpatient clinic visits to record information on previous work ups and to perform the FBB Positron Emission Tomography (PET) scan (Visit 1: screening/ baseline, Visit 2: PET scan, Visit 3: subject informed on the FBB PET scan result). At Visit 1, the initial diagnosis based on previous work up will be collected and rated on a five-point Likert confidence scale by the Physician. At Visit 2, the FBB PET scan will be performed. Adverse events will be reported during the exam and up to 7 days after the PET procedure. At Visit 3, based on the amyloid PET scan results, change of diagnosis will be collected, in addition to physician confidence.

Official Title
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Multicenter Study to Explore the Impact of Florbetaben (FBB) in Change of Diagnosis in Patients Who Are Evaluated for AD and in Whom Lumbar Puncture is Contraindicated or CSF Results Are Ambiguous

Conditions
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Alzheimer's Disease (AD)

Intervention / Treatment
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* Drug: Neuraceq (florbetaben 18F)
* Procedure: PET


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients being evaluated for Alzheimer disease and related dementias according to the HAS recommendations (atypical dementia, early onset and rapid progressive dementia) Patients who have previously been evaluated for AD and related dementias to whom a CSF examination was recommended in the last 12 months, but lumbar puncture was contraindicated or refused or CSF results were ambiguous, or Patients currently being evaluated for AD and related dementias to whom a CSF examination is recommended but lumbar puncture is contraindicated or refused Patients have a study partner who is willing and able to accompany him/her to all clinic visits for the duration of the protocol Patients able to complete all clinical visits according to the protocol Patients able to tolerate a 20-minute FBB PET scan Patient or legal representative to provide informed consent for study participation, visits and data source verification. Exclusion Criteria: The subject had a previous beta amyloid imaging scan Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol Is currently receiving any investigational pharmaceutical product or has participated in a clinical trial with an investigational pharmaceutical product within 30 days prior to screening and/or was administered a radiopharmaceutical within 10 radioactive half-lives prior to study drug administration in this study For females of childbearing age, a positive pregnancy test

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neuraceq (florbetaben 18F) PET scan<br>A single dose of 300 Megabecquerels (8.1 millicuries) Neuraceq will be administered per subject. The applied florbetaben radioactive dose will be ± 20%. | Drug: Neuraceq (florbetaben 18F)<br>* Florbetaben 18F is given as an i.v. injection followed by a flush of sodium chloride solution to ensure full delivery of the dose.<br>* Other names: FBB;Procedure: PET<br>* A brain PET scan is usually taken 90 minutes after the i.v. injection of florbetaben 18F.<br>* Other names: Positron Emission Tomography;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Change of Diagnosis Comparing Pre- and Post-scan Outcomes | The Physician's diagnosis was assessed before and after FBB PET scan. The initial Physician's diagnosis was collected before the PET scan, at Visit 1, based on key diagnostic results of current or previous workup. After the PET scan, the final Physician's diagnosis was collected at Visit 3, based on the amyloid PET scan results. | Visit 1 (baseline evaluation) and Visit 3 (up to 6 months later) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Improved Level of Physician Confidence in Diagnosis at Visit 3 | The Physician's diagnostic confidence was rated on a five-point Likert scale before and after FBB PET scan. Likert scales consisted of the categories: very weak, weak, moderate, high, and very high. | Visit 1 (baseline evaluation) and Visit 3 (up to 6 months later) | 
| Number of Participants With a Change of Management Plan Comparing Pre- and Post-scan Outcomes | For all subjects, concomitant medications were reported and any change of the management plan (e.g. new medications initiated, medications withdrawn, additional diagnostic tests ordered, referred to another specialist) was noted. | Visit 1 (baseline evaluation) and Visit 3 (up to 3 months later) | 
| Number of Subjects With Positive FBB PET Scan | PET image interpretation was performed locally in each centre by readers who had undergone training for appropriate interpretation of scans. Scans were interpreted as either positive or negative according to the approved visual assessment method. | Visit 3 (up to 6 months after baseline evaluation) | 
| Number of Subjects With Negative FBB PET Scans | PET image interpretation was performed locally in each centre by readers who had undergone training for appropriate interpretation of scans. Scans were interpreted as either positive or negative according to the approved visual assessment method. | Visit 3 (up to 6 months after baseline evaluation) | 
| Number of Subjects With Contraindicated or Failed Lumbar Puncture | Number of subjects with contraindicated or failed LP (anticoagulant therapy, thrombocytopenia, lumbar puncture failed, spinal problems) | Visit 1 (baseline evaluation) | 
| Number of Subjects With Available CSF Analysis But Results Considered as Non-contributory by the Clinician | Non-contributory CSF results (ambiguous CSF result, CSF result inconsistent with clinical information, uninterpretable CSF result for technical reasons) | Visit 1 (baseline evaluation) | 
| Number of Subjects Who Refused Lumbar Puncture. |  | Visit 1 (baseline evaluation) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CSF, Alzheimer's Disease (AD) and related dementia, HAS recommendations