Clinical Trials Register

Summary
EudraCT Number:	2021-000473-83
Sponsor's Protocol Code Number:	PET-tau-FACEHBI
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-07-29
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

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2021-000473-83

A.3

Full title of the trial

PET imaging study of the brain tau deposit in individuals with subjective cognitive
decline and mild cognitive impairment: FACEHBI cohort.

Estudio de imagen PET del depósito cerebral de tau en individuos con deterioro
cognitivo subjetivo y deterioro cognitivo leve: cohorte FACEHBI.

A.3.1

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

Brain tau deposit study in individuals with subjective cognitive decline and mild
cognitive impairment.

Estudio del depósito cerebral de tau en individuos con deterioro cognitivo subjetivo
y deterioro cognitivo leve

A.4.1

Sponsor's protocol code number

PET-tau-FACEHBI

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	Fundació ACE-Institut Català de Neurociències Aplicades
B.1.3.4	Country	Spain
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	F. Hoffmann-La Roche Ltd
B.4.2	Country	Switzerland
B.4.1	Name of organisation providing support	Life Molecular Imaging GmbH
B.4.2	Country	Germany
B.4.1	Name of organisation providing support	Fundació ACE-Institut Català de Neurociències Aplicades
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Fundació ACE-Institut Català de Neurociències Aplicades
B.5.2	Functional name of contact point	Marta Marquié Sayagués
B.5.3	Address:
B.5.3.1	Street Address	Gran via de Carles III, 85 bis
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08028
B.5.3.4	Country	Spain
B.5.4	Telephone number	34934447318
B.5.5	Fax number	34934101701
B.5.6	E-mail	mmarquie@fundacioace.org

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	No
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	[18F]-RO948
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	[18F]-RO948
D.3.9.3	Other descriptive name	[18F]RO6958948
D.3.9.4	EV Substance Code	SUB205278
D.3.10	Strength
D.3.10.1	Concentration unit	MBq megabecquerel(s)
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	370
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.IMP: 2
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	No
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	[18F]-PI-2620
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	Izaflortaucipir (18F)
D.3.9.3	Other descriptive name	[18F]-PI-2620
D.3.9.4	EV Substance Code	SUB205499
D.3.10	Strength
D.3.10.1	Concentration unit	MBq megabecquerel(s)
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	185
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

Subjective cognitive impairment and mild cognitive decline in evaluation for
diagnosis of Alzheimer's Disease.

Deterioro cognitivo subjetivo y deterioro cognitivo leve en evaluación para el
diagnóstico de enfermedad de Alzheimer.

E.1.1.1

Medical condition in easily understood language

Patients with subjective cognitive decline or mild cognitive impairment.

Pacientes con deterioro cognitivo subjetivo o deterioro cognitivo leve.

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

Comparative analysis of in vivo regional uptake of tau (quantified by PET PI-2620) between participants with subjective cognitive decline (SCD) and mild cognitive impairment (MCI), and between participants with elevated vs absent/low amyloid uptake (as quantified by PET-FBB) in the FACEHBI cohort.

Analizar diferencias en la captación regional in vivo de tau (cuantificada mediante PET-PI-2620) entre participantes con deterioro cognitivo subjetivo (DCS) y deterioro cognitivo leve (DCL), y entre participantes con captación elevada vs nula/baja de amiloide (cuantificada mediante PET-FBB) de la cohorte FACEHBI.

E.2.2

Secondary objectives of the trial

Comparative analysis of cognitive tests scores by the level of tau uptake (quantified by PET-PI-2620) in the medial temporal lobe (entorhinal, hippocampus and amygdala) of participants with SCD.
Association analysis of in vivo tau uptake and amyloid uptake (quantified by PET-florbetaben) and the worsening of cognitive tests scores / conversion to MCI in participants with SCD.
Correlation analysis between tau uptake and measurements of t-tau and p-tau in the cerebrospinal fluid of participants with SCD and MCI.
Correlation analysis between tau uptake and regional cortical thickness in participants with SCD and MCI.
Amyloid uptake threshold necessary for tau to accumulate outside the medial temporal lobe.
Incidence of adverse events (and adverse reactions).

Análisis comparativo de las puntuaciones de los test cognitivos en participantes con DCS en función del nivel de captación de tau (cuantificada mediante PET-PI-2620) en el lóbulo temporal medial (entorrinal, hipocampo y amígdala).
Analizar la relación entre la captación in vivo de tau y de amiloide (cuantificada mediante PET-Florbetaben) con el empeoramiento de los test cognitivos/conversión a DCL en participantes con DCS.
Analizar la correlación entre la captación de tau y las medidas de t-tau y p-tau en líquido cefaloraquídeo en participantes con DCS y DCL.
Analizar la correlación entre la captación de tau y el grosor cortical regional en
participantes con DCS y DCL.
Calcular el dintel de captación de amiloide necesaria para que tau se acumule fuera del lóbulo temporal medial.
Incidencia de acontecimientos y reacciones adversas.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Title: [18F] RO948-PET imaging study of the brain deposit in the FACEHBI cohort.
Protocol version 1.0 / 28thFeb2021.
Sub-study objectives:
To compare brain tau deposits between the PI2620 and RO948 PET tracers in a sample of 20 PET-Florbetaben positive FACEHBI cohort participants.
To confirm the safety of the administration of RO948 in terms of the incidence of events and adverse reactions, both during the PET scan and the subsequent follow-up.

Título: Estudio de imagen [18F]RO948-PET del depósito cerebral en la cohorte FACEHBI.
Protocolo versión 1.0 / 28feb2021.
Objetivos del sub-estudio:
Realizar una comparación directa del depósito de tau entre los trazadores de PET PI2620 y RO948 en una muestra de 20 participantes de la cohorte FACEHBI con PET-Florbetaben positivo.
Comprobar que la administración de RO948 es segura, en base a la incidencia de acontecimientos y reacciones adversas, tanto durante la realización del PET, como durante el seguimiento posterior.

E.3

Principal inclusion criteria

1. Current participation in the FACEHBI study cohort, having completed all the
procedures of visit 5 (including a PET-Florbetaben).
2. Diagnosis of subjective cognitive decline (SCD) or mild cognitive impairment (MCI). Any symptomatic treatment for AD should be maintained on a stable dosage regimen for at least 30 days before the PET scan.
3. Participant (or his/her representative) is willing to give informed consent for participation in the study.
4. In women, postmenopausal status or negative pregnancy test. Subjects (women and partners of participating men) of childbearing potential must commit to practice sexual abstinence or use highly effective contraceptive methods.
5. (Sub-study) Positive result in a previous PET-Florbetaben scan.

1. Ser participante de la cohorte del estudio FACEHBI, habiendo completado todos los procedimientos de la visita 5 del mismo (incluido el PET-FBB).
2. Tener un diagnóstico de deterioro cognitivo subjetivo (DCS) o deterioro cognitivo leve (DCL). Si el sujeto recibe tratamiento sintomático para la EA, éste debe mantenerse en un régimen de dosificación estable durante al menos 30 días antes de realización del PET-PI-2620 (y en su caso del PET-RO948).
3. Otorgar consentimiento para participar en el estudio.
4. En mujeres, estado postmenopáusico o prueba de embarazo negativa. Sujetos (mujeres y parejas de hombres participantes) en edad fértil deben aceptar el compromiso de practicar la abstinencia sexual o utilizar métodos anticonceptivos altamente efectivos.
5. (Subestudio) Resultado positivo en el PET-FBB realizado en la visita 5 del estudio FACEHBI.

E.4

Principal exclusion criteria

1. Severe sensory disturbances (visual or auditory) that may interfere with
performance in neuropsychological tests.
2. Any previous or planned tests applying radiopharmaceuticals within 6 months prior to, or the 12 months following inclusion in the study.
3. Pregnant or lactating women.
4. Any medical or personal circumstances that prevent the subject from completing the 3-year follow-up period of the FACEHBI study.
5. Clinically relevant hematologic, liver, respiratory, cardiovascular, renal, metabolic, endocrine, or central nervous system (CNS) disease or other medical conditions that are not well controlled and that may put the subject at risk or interfere with the study objectives.
6. Contraindications to magnetic resonance imaging, such as the
presence of pacemakers, defibrillators, metal prostheses, or claustrophobia.
7. History of alcoholism or drug dependence in the last 2 years before inclusion.
8. Medical history of hypersensitivity or allergy to [18F] PI-2620 (and [18F] RO948 in the substudy) or its derivatives.
9. Treatment with any other investigational drug within 30 days prior to inclusion.

1. Individuos con alteraciones sensoriales (visuales u auditivas) severas que
interfieran en la realización de las pruebas neuropsicológicas.
2. Sujetos que, pormotivos médicos, se hayan realizado o tengan programado realizarse otras pruebas con uso de radiofármacos en los 6 meses previos, o los 12 meses siguientes a su inclusión en el estudio.
3. Mujeres embarazadas o en periodo de lactancia.
4. Sujetos que, debido a circunstancias médicas o personales, no quieran o puedan continuar el seguimiento dentro del estudio FACEHBI durante los 3 siguientes años.
5. Enfermedad hematológica, hepática, respiratoria, cardiovascular, renal,
metabólica, endocrina o del sistema nervioso central (SNC) clínicamente relevante u otras afecciones médicas que no estén bien controladas y que puedan poner al sujeto en riesgo o interferir con los objetivos del estudio. 6. Contraindicación a la realización de resonancia magnética como la presencia de marcapasos, desfibriladores, prótesis metálicas, o la claustrofobia.
7. Antecedentes de alcoholismo o drogodependencia en los últimos 2 años antes de la inclusión.
8. Sospecha o historial de hipersensibilidad o alergia a [18F] PI-2620 (y [18F] RO948 en el subestudio) o sus derivados.
9. Tratamiento con cualquier otro medicamento en investigación en los 30 días anteriores a la inclusión.

E.5 End points

E.5.1

Primary end point(s)

Comparative differences in the levels and localization of brain tau protein aggregates (quantified by PET-PI2620) in patients with SCD versus MCI, and those
with a positive versus a negative result in a PET-Florbetaben.

Diferencias de niveles y localización de agregados de proteína tau cerebrales
(cuantificados mediante PET-PI2620) entre participantes con DCS versus DCL, y
entre aquellos con un PET-Florbetaben positivo versus negativo.

E.5.1.1

Timepoint(s) of evaluation of this end point

0, 1, 2 and 3 years

0, 1, 2 y 3 años

E.5.2

Secondary end point(s)

PET-PI-2620 exploratory variables.
PET-RO948 exploratory variables (sub-study).
PET- Florbetaben exploratory variables.
Neuropsychological variables (cognitive and learning assessments).
Syndromic diagnosis (SCD or MCI, according to neuropsychological tests results). Incidence of adverse events and adverse reactions.

Variables exploratorias del PET-PI-2620.
Variables exploratorias del PET-RO-948.
Variables exploratorias del PET-Florbetaben .
Variables neuropsicológicas (tests cognitivos y de aprendizaje).
Diagnóstico sindrómico (DCS o DCL, en base a los resultados de los tests neuropsicológicos).
Incidencia de acontecimientos adversos y reacciones adversas

E.5.2.1

Timepoint(s) of evaluation of this end point

0, 7 days, 30 days; 1, 2 and 3 years

0, 7 días, 30 días; 1, 2 y 3 años

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

Yes

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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.8.3

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.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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

Last patient, last visit

Ultimo paciente, ultima visita

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

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

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

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

100

F.4.2

For a multinational trial

F.4.2.1

In the EEA

100

F.4.2.2

In the whole clinical trial

100

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)

Standard of care

Tratamiento según práctica clínica habitual

G. Investigator Networks to be involved in the Trial

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-12-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-11-19

P. End of Trial
P.	End of Trial Status	Ongoing

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