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

• Sponsor: Piramal Imaging Limited (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02681172
• Collaborator: (none)
• Enrollment: 218
• Location: 1
• Arm: 1
• Duration (Months): 13
• Patients Per Site Per Month: 16.7

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease (AD)	Drug: Neuraceq (florbetaben 18F); Procedure: PET	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 218 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Health Services Research
• Official Title: 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
• Study Start Date: Oct 1, 2015
• Actual Primary Completion Date: Sep 1, 2016
• Actual Study Completion Date: Nov 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Neuraceq (florbetaben 18F) PET scan 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); Florbetaben 18F is given as an i.v. injection followed by a flush of sodium chloride solution to ensure full delivery of the dose.; Other Names: FBB ; Procedure: PET; A brain PET scan is usually taken 90 minutes after the i.v. injection of florbetaben 18F.; Other Names: Positron Emission Tomography

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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".

2. 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.

3. 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.

4. 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.

5. 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)

6. 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)

7. Number of Subjects Who Refused Lumbar Puncture. [Visit 1 (baseline evaluation)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Coordinating center (Hôpital de La Timone) and 18 associated centers in France	Marseille		France	13385

Sponsors and Collaborators

• Piramal Imaging Limited

Investigators

• Principal Investigator: Mathieu Ceccaldi, Prof. MD., Hôpital de La Timone, Marseille, France
• Principal Investigator: Eric Guedj, Prof., Hôpital de la Timone, Marseille, France

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Piramal Imaging Limited
• ClinicalTrials.gov Identifier: NCT02681172
• Other Study ID Numbers: FBB_01_02_2015; 2015-002606-37
• First Posted: Feb 12, 2016
• Last Update Posted: Nov 2, 2018
• Last Verified: Mar 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Piramal Imaging Limited: CSF; Alzheimer's Disease (AD) and related dementia; HAS recommendations
• Additional relevant MeSH terms: Alzheimer Disease

Study Results

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.

Arm/Group Title	Neuraceq (Florbetaben 18F) PET Scan
Arm/Group Description	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.
Period Title: Overall Study
STARTED	218
Safety Analysis Set	205
Full Analysis Set	205
Per Protocol Set	205
COMPLETED	205
NOT COMPLETED	13

Baseline Characteristics

Arm/Group Title	Neuraceq (Florbetaben 18F) PET Scan
Arm/Group Description	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.
Overall Participants	205
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	70.9 (9.7)
Sex: Female, Male (Count of Participants)
Female	102 49.8%
Male	103 50.2%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With a Change of Diagnosis Comparing Pre- and Post-scan Outcomes
Description	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)

Outcome Measure Data

Analysis Population Description

All subjects who received any amount of florbetaben were included in the Safety analysis set

Arm/Group Title	Safety Analysis Set
Arm/Group Description	All subjects who received any amount of florbetaben were included.
Measure Participants	205
Count of Participants [Participants]	137 66.8%

2. Secondary Outcome

Title	Number of Subjects With Improved Level of Physician Confidence in Diagnosis at Visit 3
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Safety Analysis Set
Arm/Group Description	All subjects who received any amount of florbetaben were included.
Measure Participants	205
Count of Participants [Participants]	167 81.5%

3. Secondary Outcome

Title	Number of Participants With a Change of Management Plan Comparing Pre- and Post-scan Outcomes
Description	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)

Outcome Measure Data

Analysis Population Description

All subjects who received any amount of florbetaben were included in the Safety analysis set.

Arm/Group Title	Safety Analysis Set
Arm/Group Description	All subjects who received any amount of florbetaben were included.
Measure Participants	205
Count of Participants [Participants]	164 80%

4. Secondary Outcome

Title	Number of Subjects With Positive FBB PET Scan
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Safety Analysis Set
Arm/Group Description	All subjects who received any amount of florbetaben were included.
Measure Participants	205
Count of Participants [Participants]	132 64.4%

5. Secondary Outcome

Title	Number of Subjects With Negative FBB PET Scans
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Safety Analysis Set
Arm/Group Description	All subjects who received any amount of florbetaben were included.
Measure Participants	205
Count of Participants [Participants]	73 35.6%

6. Secondary Outcome

Title	Number of Subjects With Contraindicated or Failed Lumbar Puncture
Description	Number of subjects with contraindicated or failed LP (anticoagulant therapy, thrombocytopenia, lumbar puncture failed, spinal problems)
Time Frame	Visit 1 (baseline evaluation)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Safety Analysis Set
Arm/Group Description	All subjects who received any amount of florbetaben were included.
Measure Participants	205
Count of Participants [Participants]	45 22%

7. Secondary Outcome

Title	Number of Subjects With Available CSF Analysis But Results Considered as Non-contributory by the Clinician
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Safety Analysis Set
Arm/Group Description	All subjects who received any amount of florbetaben were included.
Measure Participants	205
Count of Participants [Participants]	87 42.4%

8. Secondary Outcome

Title	Number of Subjects Who Refused Lumbar Puncture.
Time Frame	Visit 1 (baseline evaluation)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Safety Analysis Set
Arm/Group Description	All subjects who received any amount of florbetaben were included.
Measure Participants	205
Count of Participants [Participants]	75 36.6%

Adverse Events

Time Frame	Adverse events were captured for up to 7 days after the PET scan procedure.
Arm/Group Title	Safety Analysis Set
Arm/Group Description	All subjects who received any amount of florbetaben were included.
All Cause Mortality
	Safety Analysis Set
	Affected / at Risk (%)	# Events
Total	0/205 (0%)
Serious Adverse Events
	Safety Analysis Set
	Affected / at Risk (%)	# Events
Total	1/205 (0.5%)
Nervous system disorders
Cerebellar infarct	1/205 (0.5%)	1
Other (Not Including Serious) Adverse Events
	Safety Analysis Set
	Affected / at Risk (%)	# Events
Total	21/205 (10.2%)
Eye disorders
Glaucoma	1/205 (0.5%)	1
Gastrointestinal disorders
Nausea	1/205 (0.5%)	1
General disorders
Fatigue	1/205 (0.5%)	1
Inflammation	1/205 (0.5%)	1
Injection Site Haematoma	2/205 (1%)	2
Injection Site Pain	4/205 (2%)	4
Injection Site Paraesthesia	5/205 (2.4%)	5
Metabolism and nutrition disorders
Dehydration	1/205 (0.5%)	1
Musculoskeletal and connective tissue disorders
Polymyalgia Rheumatica	1/205 (0.5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm malignant	1/205 (0.5%)	1
Nervous system disorders
Cerebellar infarction	1/205 (0.5%)	1
Headache	1/205 (0.5%)	1
Psychiatric disorders
Confusional State	1/205 (0.5%)	1
Renal and urinary disorders
Acute Kidney injury	1/205 (0.5%)	1
Skin and subcutaneous tissue disorders
Erythema	1/205 (0.5%)	1
Pruritus	1/205 (0.5%)	1
Skin Ulcer	1/205 (0.5%)	1
Surgical and medical procedures
Cataract operation	1/205 (0.5%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.