Clinical Trials Register

Summary
EudraCT Number:	2017-002527-21
Sponsor's Protocol Code Number:	AMYPAD-01
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2018-04-24
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2017-002527-21

A.3

Full title of the trial

Multicentre, Open-label, Randomised Study to Assess the Diagnostic Value of Amyloid PET Imaging in Patients with Subjective Cognitive Decline Plus, Mild Cognitive Impairment, or Dementia Where Alzheimer’s Disease is in the Differential Diagnosis

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Diagnostic and Patient Management Study

A.3.2

Name or abbreviated title of the trial where available

DPMS

A.4.1

Sponsor's protocol code number

AMYPAD-01

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	University of Geneva
B.1.3.4	Country	Switzerland
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Innovative Medicines Initiative 2 Joint Undertaking
B.4.2	Country	Belgium
B.4.1	Name of organisation providing support	EFPIA (from Janssen Pharmaceutical)
B.4.2	Country	Belgium
B.4.1	Name of organisation providing support	EFPIA (from Piramal Imaging)
B.4.2	Country	United Kingdom
B.4.1	Name of organisation providing support	EFPIA (from GE Healthcare)
B.4.2	Country	United Kingdom
B.4.1	Name of organisation providing support	SECRETARIAT D'ETAT A LA FORMATION A LA RECHERCHE ET A L'INNOVATION (SEFRI)
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	University of Geneva
B.5.2	Functional name of contact point	LANVIE
B.5.3	Address:
B.5.3.1	Street Address	Chemin du Petit-Bel-Air 2
B.5.3.2	Town/ city	Chêne Bourg
B.5.3.3	Post code	1225
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	00412230 54758
B.5.6	E-mail	giovanni.frisoni@gmail.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Neuraceq
D.2.1.1.2	Name of the Marketing Authorisation holder	Piramal Imaging Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Neuraceq
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Florbetaben
D.3.9.1	CAS number	902143-01-5
D.3.9.3	Other descriptive name	FLORBETABEN (18F)
D.3.9.4	EV Substance Code	SUB119774
D.3.10	Strength
D.3.10.1	Concentration unit	MBq/ml megabecquerel(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	300
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	Yes
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Alzheimer's disease
Mild Cognitive Impairment
Subjective Cognitive Decline Plus

E.1.1.1

Medical condition in easily understood language

Alzheimer’s disease (AD) is a progressive disorder and it is the most common cause of cognitive impairment and dementia.

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To test the hypothesis that the proportion of subjects for whom the managing physician reaches an aetiologic diagnosis with very high confidence (≥90%) at 12 weeks after baseline is higher for subjects who underwent amyloid PET imaging shortly after baseline than for subjects who have not yet undergone amyloid PET imaging (ie, subjects scheduled to undergo amyloid PET imaging at 8 months [±8 weeks] after baseline).

E.2.2

Secondary objectives of the trial

1) To assess the impact of amyloid PET imaging on Diagnosis and confidence (Time to communicate to the patient an aetiologic diagnosis with very high confidence (≥90%); Changes in the managing physician’s aetiologic diagnosis and diagnostic confidence over time; and the managing physician’s estimate of the likelihood that the patient’s symptoms are due to AD.
2) To assess the impact of amyloid PET imaging on diagnostic and patient management, including: change or early adoption of programs and pharmacologic treatments aimed to delay the onset or progression of cognitive impairment; and Use of medical resources.
3) To assess the impact of amyloid PET imaging on:
• Patient-related outcomes (cognition, anxiety, depression, coping skills, and quality of life)
• Cost of diagnostic workup to the aetiologic diagnosis with very high confidence (≥90%)
• Number of patients who are discharged from the memory centre and the reason for discharge
4) Imaging results assessment

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• The patient can be male or female and of any race or ethnicity.
• The patient must be 60 to 85 years of age (for patients with SCD-Plus) or 50 to 85 years of age (for patients with MCI or with dementia where AD is in the differential diagnosis).
• The patient must have a complaint (reported by the patient or by a caregiver) of cognitive problems that are considered by the managing physician to be possibly due to AD.
o The patient must be entering a diagnostic assessment for the cognitive complaint.
o The patient’s managing physician at the memory clinic must feel that knowledge of the patient’s brain amyloid status may increase diagnostic confidence and alter diagnosis and management.
o In some centres, the patient may receive diagnostic workup before being screened for this study. These patients can be enrolled in the study; however, if they are assigned to the Early Amyloid PET Imaging arm, the results of that workup must not be made available to the managing physician before the managing physician reviews the results of the amyloid PET scan.
• The patient must satisfy the diagnostic criteria for one of the following:
o SCD-Plus
o MCI
o Dementia, where AD is in the differential diagnosis
• The patient has an MRI and/or CT scan that excludes an intracranial mass or other lesion(s) that could explain cognitive impairment.
• The patient can complete all clinical visits according to the protocol.
• The patient can tolerate a 20-minute amyloid PET scan.
• The patient (or a legally acceptable representative, for patients with dementia) provides informed consent for study participation and data source verification.
• If the patient has dementia, he or she has a study partner willing and able to accompany him or her to all visits for the duration of the protocol

E.4

Principal exclusion criteria

Subjects must be excluded from participating in this study if they meet any of the following criteria:
• The patient has another confirmed condition that can fully account for the cognitive impairment (neuroinflammatory, neuroinfective, or neurodegenerative disease; multiple sclerosis; genetic disorders; HIV; brain injuries; neurosurgery aftereffects; major depressive episode; schizoaffective disorder; delusional disorder; delirium)
• The patient came to observation of the memory clinic for reasons other than diagnosis (disability assessment for social aids, cognitive assessment for driving license, etc.)
• The patient had a previous beta-amyloid imaging scan and/or has had other diagnostic workup (fluorodeoxyglucose [FDG]-PET and/or cerebrospinal fluid [CSF] analysis) for a cognitive complaint prior to the screening. (In some centres, the patient may receive a diagnostic workup before the screening for this study. These patients can be enrolled in the study only if the investigator is blinded to the results of those tests until after randomization. For subjects assigned to the Early Amyloid PET Imaging arm, the managing physician will be blinded to the results of those tests until he or she has reviewed the results of the amyloid PET imaging.
• The patient has any life-threatening unstable medical disease or psychiatric condition that could lead to difficulty in complying with the protocol.
• The patient is currently receiving an 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.
• The patient is a woman who is pregnant, planning to become pregnant, or lactating.

E.5 End points

E.5.1

Primary end point(s)

The difference, at 12 weeks after baseline, between the Early Amyloid PET Imaging arm and the Late Amyloid PET Imaging arm in the proportion of patients for whom the managing physician has made an aetiologic diagnosis with very high confidence (≥90%). Diagnostic confidence, which is the managing physician’s confidence that the diagnosis is correct, will be measured with a visual analogue scale (VAS) from 0% (no confidence) to 100% (full confidence).

E.5.1.1

Timepoint(s) of evaluation of this end point

At 12 weeks after Baseline

E.5.2

Secondary end point(s)

Diagnosis and Confidence
• The difference between the Early Amyloid PET Imaging arm and the Late Amyloid PET Imaging arm in the time (from baseline) to communicate to the patient an aetiologic diagnosis with very high confidence (≥90%).
• ‘The changes in the managing physician’s aetiologic diagnosis at T3 vs T2 vs T1 in each arm.
• The changes in the managing physician’s diagnostic confidence at T3 vs T2 vs T1 vs T0 in the Early Amyloid PET Imaging arm vs the Late Amyloid PET Imaging arm.
• The managing physician’s estimate of the likelihood that the patient’s symptoms are due to AD at T3 vs T2 vs T1 vs T0 in the Early Amyloid PET Imaging arm vs the Late Amyloid PET Imaging arm.
• Changes over calendar time in the placement of amyloid PET imaging in the patient workup for subjects in the Free Choice Amyloid PET Imaging arm.

Patient Management
• The difference between arms (Early Amyloid PET Imaging arm, the Late Amyloid PET Imaging arm, or the Free Choice Amyloid PET Imaging arm) in the number of patients randomised to disease-modifying drug (DMD) or any other AD clinical trial at T2.
• The difference between the Early Amyloid PET Imaging arm and the Late Amyloid PET Imaging arm in number of subjects with changes in the management plan (changes in or start of a new program or pharmacologic treatment) at T1 vs T2 vs T3.

• Health Economics and Outcomes Research (HEOR) The impact on patient-related outcomes (cognition, anxiety, depression, coping skills, and quality of life) at T3 vs T2 vs T0 in each arm
• The difference in the cost of diagnostic workup to the aetiologic diagnosis with very high confidence (≥90%) in the Early Amyloid PET Imaging arm vs the Late Amyloid PET Imaging arm. (In those centres where the subjects in the Early Amyloid PET Imaging arm receive a diagnostic workup in addition to clinical evaluation before baseline, the relative costs will not be considered if the results of those exams are not known by the managing physician before the managing physician makes the aetiologic diagnosis.)
• Differences in the use of medical resources (not limited to diagnostic procedures, tests, visits, and hospitalisations) and programs between Early Amyloid PET Imaging and Late Amyloid PET Imaging arms.
• The number of patients who withdraw from the study and the reasons for withdrawal.

Imaging Results Assessment
• Descriptive analysis of local visual assessment results
• Mean values of quantitative image assessments (composite cortical standardised uptake value ratios [SUVR] and converted to the centiloid scale) across amyloid PET tracers and by diagnostic subgroup.
• The composite cortical quantitative uptake (SUVR and SUVR converted to the centiloid scale) vs visual reading interpretation
• For each of the amyloid PET tracers, the differences in regional quantitative uptake between diagnostic strata.

For subjects in the Early Amyloid PET Imaging arm who have a second amyloid PET scan:
• The longitudinal development of quantitative image assessments (regional and composite cortical SUVR and SUVR converted to the centiloid scale)
• The difference in amyloid load, as indicated by quantitative image assessments, between the first and the second amyloid PET scan

E.5.2.1

Timepoint(s) of evaluation of this end point

The timepoints are defined as follows: T0 = baseline, T1 = 12 weeks after T0, T2 = 6 months (±14 days) after T0, T3 = 13 months (±4 weeks) after T0; T4 = ≤28 days after the second scan, which will be approximately 18 months after T0. (All time points are calculated relative to baseline.)

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

European Union

Switzerland

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

250

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

650

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Patients with dementia may be unable to give consent. In this case, a legally acceptable representative, for patients with dementia, has to provide informed consent

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

112

F.4.2

For a multinational trial

F.4.2.1

In the EEA

784

F.4.2.2

In the whole clinical trial

900

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	Stichting VUmc
G.4.3.4	Network Country	Netherlands
G.4 Investigator Network to be involved in the Trial: 2
G.4.1	Name of Organisation	The University of Edinburgh
G.4.3.4	Network Country	United Kingdom
G.4 Investigator Network to be involved in the Trial: 3
G.4.1	Name of Organisation	Barcelonabeta Brain Research Center
G.4.3.4	Network Country	Spain
G.4 Investigator Network to be involved in the Trial: 4
G.4.1	Name of Organisation	Karolinska Institutet
G.4.3.4	Network Country	Sweden
G.4 Investigator Network to be involved in the Trial: 5
G.4.1	Name of Organisation	Centre Hospitalier Universitaire de Toulouse
G.4.3.4	Network Country	France
G.4 Investigator Network to be involved in the Trial: 6
G.4.1	Name of Organisation	University College London
G.4.3.4	Network Country	United Kingdom
G.4 Investigator Network to be involved in the Trial: 7
G.4.1	Name of Organisation	University Hospital of Cologne
G.4.3.4	Network Country	Germany
G.4 Investigator Network to be involved in the Trial: 8
G.4.1	Name of Organisation	Stichting Katholieke Universiteit
G.4.3.4	Network Country	Netherlands

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2018-08-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-07-03

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-09-30

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials