Alzheimer's Disease (AD)
Conditions
Keywords
CSF, Alzheimer's Disease (AD) and related dementia, HAS recommendations
Brief summary
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: 1. lumbar puncture was not feasible for medical conditions 2. results of cerebrospinal fluid (CSF) analysis were considered ambiguous by treating physicians 3. lumbar puncture (LP) was refused by the patient
Detailed description
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: 1. lumbar puncture was not feasible for medical conditions 2. results of cerebrospinal fluid (CSF) analysis were considered ambiguous by treating physicians 3. 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.
Interventions
DRUGNeuraceq (florbetaben 18F)
Florbetaben 18F is given as an i.v. injection followed by a flush of sodium chloride solution to ensure full delivery of the dose.
PROCEDUREPET
A brain PET scan is usually taken 90 minutes after the i.v. injection of florbetaben 18F.
Sponsors
Piramal Imaging Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Change of Diagnosis Comparing Pre- and Post-scan Outcomes | Visit 1 (baseline evaluation) and Visit 3 (up to 6 months later) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Change of Management Plan Comparing Pre- and Post-scan Outcomes | Visit 1 (baseline evaluation) and Visit 3 (up to 3 months later) | 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. |
| Number of Subjects With Positive FBB PET Scan | Visit 3 (up to 6 months after baseline evaluation) | 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. |
| Number of Subjects With Negative FBB PET Scans | Visit 3 (up to 6 months after baseline evaluation) | 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. |
| Number of Subjects With Improved Level of Physician Confidence in Diagnosis at Visit 3 | Visit 1 (baseline evaluation) and Visit 3 (up to 6 months later) | 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. |
| Number of Subjects With Available CSF Analysis But Results Considered as Non-contributory by the Clinician | Visit 1 (baseline evaluation) | Non-contributory CSF results (ambiguous CSF result, CSF result inconsistent with clinical information, uninterpretable CSF result for technical reasons) |
| Number of Subjects Who Refused Lumbar Puncture. | Visit 1 (baseline evaluation) | — |
| Number of Subjects With Contraindicated or Failed Lumbar Puncture | Visit 1 (baseline evaluation) | Number of subjects with contraindicated or failed LP (anticoagulant therapy, thrombocytopenia, lumbar puncture failed, spinal problems) |
Countries
France
Participant flow
Recruitment details
This was a Phase IV, multi-center study which was conducted in an outpatient setting documenting routine clinical care in the Centres Mémoire Ressources et Recherches (CMRR). Subjects were recruited in 18 active centers in France.
Participants by arm
| Arm | Count |
|---|---|
| Neuraceq (Florbetaben 18F) PET Scan A single dose of 300 Megabecquerels (8.1 millicuries) Neuraceq was administered per subject. The applied florbetaben radioactive dose was ± 20%. Neuraceq (florbetaben 18F): Florbetaben 18F was given as an i.v. injection followed by a flush of sodium chloride solution to ensure full delivery of the dose. PET: A brain PET scan was taken 90 minutes after the i.v. injection of florbetaben 18F. | 205 |
| Total | 205 |
Baseline characteristics
| Characteristic | Neuraceq (Florbetaben 18F) PET Scan |
|---|---|
| Age, Continuous | 70.9 years STANDARD_DEVIATION 9.7 |
| Sex: Female, Male Female | 102 Participants |
| Sex: Female, Male Male | 103 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 205 |
| other Total, other adverse events | 21 / 205 |
| serious Total, serious adverse events | 1 / 205 |
Outcome results
Primary
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.
Time frame: Visit 1 (baseline evaluation) and Visit 3 (up to 6 months later)
Population: All subjects who received any amount of florbetaben were included in the Safety analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Safety Analysis Set | Number of Participants With a Change of Diagnosis Comparing Pre- and Post-scan Outcomes | 137 Participants |
Secondary
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.
Time frame: Visit 1 (baseline evaluation) and Visit 3 (up to 3 months later)
Population: All subjects who received any amount of florbetaben were included in the Safety analysis set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Safety Analysis Set | Number of Participants With a Change of Management Plan Comparing Pre- and Post-scan Outcomes | 164 Participants |
Secondary
Number of Subjects Who Refused Lumbar Puncture.
Time frame: Visit 1 (baseline evaluation)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Safety Analysis Set | Number of Subjects Who Refused Lumbar Puncture. | 75 Participants |
Secondary
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)
Time frame: Visit 1 (baseline evaluation)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Safety Analysis Set | Number of Subjects With Available CSF Analysis But Results Considered as Non-contributory by the Clinician | 87 Participants |
Secondary
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)
Time frame: Visit 1 (baseline evaluation)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Safety Analysis Set | Number of Subjects With Contraindicated or Failed Lumbar Puncture | 45 Participants |
Secondary
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.
Time frame: Visit 1 (baseline evaluation) and Visit 3 (up to 6 months later)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Safety Analysis Set | Number of Subjects With Improved Level of Physician Confidence in Diagnosis at Visit 3 | 167 Participants |
Secondary
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.
Time frame: Visit 3 (up to 6 months after baseline evaluation)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Safety Analysis Set | Number of Subjects With Negative FBB PET Scans | 73 Participants |
Secondary
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.
Time frame: Visit 3 (up to 6 months after baseline evaluation)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Safety Analysis Set | Number of Subjects With Positive FBB PET Scan | 132 Participants |