Clinical Trials Register

Summary
EudraCT Number:	2018-002102-31
Sponsor's Protocol Code Number:	221AD205
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2018-11-23
Trial results	View 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

2018-002102-31

A.3

Full title of the trial

A Phase 2, Multicenter, Randomized, Parallel-Group, Double-Blind,
Controlled Study of Aducanumab (BIIB037) in Subjects With Mild Cognitive Impairment
due to Alzheimer’s Disease or With Mild Alzheimer’s Disease Dementia to Evaluate the
Safety of Continued Dosing in Subjects with Asymptomatic Amyloid-Related Imaging
Abnormalities

Estudio en fase II, multicéntrico, aleatorizado, doble ciego, controlado y de grupos paralelos de Aducanumab (BIIB037) en sujetos con deterioro cognitivo leve debido a la enfermedad de Alzheimer o con demencia de la enfermedad de Alzheimer leve para evaluar la seguridad de la administración de dosis continuada en sujetos asintomáticos con anomalías en las imágenes relacionadas con el amiloide.

A.3.1

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

A Study of Aducanumab in Participants With Mild
Cognitive Impairment due to Alzheimer’s Disease or
With Mild Alzheimer’s Disease Dementia to Evaluate the
Safety of Continued Dosing in Participants With
Asymptomatic Amyloid-Related Imaging Abnormalities

Estudio de Aducanumab (BIIB037) en sujetos con deterioro cognitivo leve debido a la enfermedad de Alzheimer o con demencia de la enfermedad de Alzheimer leve para evaluar la seguridad de la administración de dosis continuada en sujetos asintomáticos con anomalías en las imágenes relacionadas con el amiloide.

A.4.1

Sponsor's protocol code number

221AD205

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02477800

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	Biogen Idec Research Limited
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Biogen Idec Research Limited
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Biogen Idec Research Limited
B.5.2	Functional name of contact point	Biogen España
B.5.3	Address:
B.5.3.1	Street Address	Paseo de la Castellana, 41
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28046
B.5.3.4	Country	Spain
B.5.4	Telephone number	0034913107110
B.5.5	Fax number	0034913107181
B.5.6	E-mail	clinicaltrials@biogen.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	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	Aducanumab
D.3.2	Product code	BIIB037
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
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	Aducanumab
D.3.9.1	CAS number	N/A
D.3.9.2	Current sponsor code	BIIB037
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	No
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	Yes
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	Yes
D.3.11.13.1	Other medicinal product type	recombinant monoclonal antibody

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection/infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Mild Cognitive Impairment due to Alzheimer's Disease and Mild Alzheimer's Dementia

Deterioro cognitivo leve debido a la enfermedad de Alzheimer o con demencia de la enfermedad de Alzheimer leve.

E.1.1.1

Medical condition in easily understood language

Mild Cognitive Impairment due to Alzheimer's Disease and Mild Alzheimer's Dementia

Deterioro cognitivo leve debido a la enfermedad de Alzheimer o con demencia de la enfermedad de Alzheimer leve.

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10001896
E.1.2	Term	Alzheimer's disease
E.1.2	System Organ Class	100000004852

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial


The primary objective of the study is to assess the safety impact of continuing aducanumab dosing in
asymptomatic Amyloid-related Imaging Abnormalities
(ARIA) in participants with mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) or with mild AD dementia.

El objetivo principal del estudio es evaluar el impacto en la seguridad de continuar la administración de la dosis de aducanumab en las ARIA asintomáticas en sujetos con DCL debido a EA o con demencia de la EA leve.

E.2.2

Secondary objectives of the trial

The secondary objective of the study is to characterize ARIA, from both the imaging and the clinical perspective and to characterize the safety, tolerability, pharmacokinetics (PK), and immunogenicity of aducanumab.

Caracterizar las ARIA, tanto desde la perspectiva de las imágenes diagnósticas como de la perspectiva clínica y caracterizar la seguridad, tolerabilidad, farmacocinética (FC) y la inmunogenia de aducanumab.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Key Inclusion Criteria:
• Ability of the participant or his/her legally authorized representative to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use confidential
health information in accordance with national and local
participant privacy regulations.
• Must have at least 6 years of education or work
experience to exclude mental deficits other than MCI
due to AD or mild AD dementia.
• Must have evidence of cerebral Aβ accumulation, based on a positive PET scan of the brain. Previously obtained positron emission tomography (PET) scan
(within 12 months of screening) is permissible. Previous PET scan images must be submitted to the central imaging vendor to confirm that study inclusion criteria
are met.
• Must consent to apolipoprotein E (ApoE) genotyping.
• Must meet all of the following clinical criteria for MCI due to AD or mild AD dementia according to NIAAA criteria [Albert 2011; McKhann 2011], and must have
the following: MCI due to AD (a CDR global score of 0.5, and an MMSE score between 24 and 30
(inclusive)), and Mild AD dementia (a CDR global score of 0.5 or 1, and as MMSE score between 20 and 26 (inclusive)).

Criterios de Inclusión Principales:
- Capacidad del sujeto o su representante legal para comprender el objetivo y los riesgos del estudio, así como facilitar el consentimiento informado firmado y fechado, y la autorización para usar información sanitaria confidencial de acuerdo con las normativas nacionales y locales sobre la privacidad de los sujetos.
- Debe tener al menos 6 años de experiencia en el sistema educativo o laboral con el fin de excluir deficiencias mentales distintas al DCL debido a EA o demencia de la EA leve.
- Debe presentar indicios de acumulación de Aβ cerebral, en base a un resultado positivo en la exploración por TEP del cerebro. Una TEP obtenida anteriormente (en los 12 meses anteriores a la selección) es aceptable. Las imágenes de las TEP anteriores deben enviarse al proveedor central de diagnóstico por la imagen para confirmar que se cumplen los criterios de inclusión del estudio.
- Debe dar consentimiento para la genotipificación de la ApoE.
- Debe cumplir todos los criterios clínicos siguientes de DCL debido a EA o demencia de la EA leve de acuerdo con los criterios del Instituto Nacional sobre el Envejecimiento y la Asociación de Alzheimer (National Institute on Aging-Alzheimer's Association, NIA-AA) [Albert 2011; McKhann 2011] y deben presentar lo que sigue: DCL debido a EA (Una puntuación global de la CDR de 0,5, y una puntuación del MMSE de entre 24 y 30 (ambas inclusive)), y Demencia de la EA leve (Una puntuación global de la CDR de 0,5 o 1 y Una puntuación del MMSE de entre 20 y 26 (ambas inclusive)).

E.4

Principal exclusion criteria

Key Exclusion Criteria:
• Any uncontrolled medical or
neurological/neurodegenerative condition (other than AD) that, in the opinion of the Investigator, might be a contributing cause of the participant’s cognitive
impairment (e.g., substance abuse, vitamin B12 deficiency, abnormal thyroid function, stroke or other cerebrovascular condition, Lewy body dementia,
frontotemporal dementia, head trauma).
• Clinically significant unstable psychiatric illness
(e.g., uncontrolled major depression, uncontrolled
schizophrenia, uncontrolled bipolar affective disorder)
within 6 months prior to Screening.
• Transient ischemic attack or stroke or any
unexplained loss of consciousness within 1 year prior to Screening.
• Vaccinations within 10 days prior to randomization (Day 1).
• Female participants who are pregnant or currently breastfeeding.

Criterios de Exclusión Principales:
- Cualquier afección médica o neurológica/neurodegenerativa no controlada (distinta de la EA) que, en opinión del investigador, pudiera ser una causa que contribuye al deterioro cognitivo del sujeto (p. ej., abuso de sustancias, déficit de vitamina B12, función tiroidea anómala, accidente cerebrovascular u otro trastorno cerebrovascular, demencia con cuerpos de Lewy, demencia frontotemporal, traumatismo craneal).
- Enfermedad psiquiátrica inestable clínicamente significativa (p. ej., depresión mayor no controlada, esquizofrenia no controlada, trastorno afectivo bipolar no controlado) en los 6 meses anteriores a la selección.
- Accidente isquémico transitorio, accidente cerebrovascular o pérdida de conciencia sin explicación en el plazo de 1 año antes de la selección.
- Vacunas en el plazo de 10 días antes de la aleatorización (día 1).
- Sujetos de sexo femenino que estén embarazadas o en periodo de lactancia.

E.5 End points

E.5.1

Primary end point(s)

Primary endpoint:
Number of Clinically Impactful
Amyloid-related Imaging
Abnormalities (ARIA)

Clinically impactful ARIA is
defined as symptoms and/or
signs associated with ARIA
that are life threatening,
require hospitalization, and/or
result in persistent or
significant disability as
assessed by the independent
Adjudication Committee.

Criterios de Valoración principal:
El criterio de valoración principal relacionado con este objetivo es la incidencia de las ARIA clínicamente significativas, definidas como síntomas y/o signos asociados con ARIA que son potencialmente mortales, que requieran hospitalización y/o provocan discapacidad persistente o significativa, según lo evaluado por el Comité de adjudicación independiente.

E.5.1.1

Timepoint(s) of evaluation of this end point

Primary endpoint:
Baseline up to Week 54

Valoración principal:
Desde la visita Basal hasta la semana 54

E.5.2

Secondary end point(s)

1. Number of Participants With
ARIA by Severity as Obtained
on Magnetic Resonance
Imaging (MRI)
2. Time to Onset of ARIA as
Obtained on MRI
3. Time to Resolution of ARIA as
Obtained on MRI
4. Number of Participants With
Symptomatic ARIA by Severity
5. Time to Onset of Symptomatic
ARIA
6. Time to Resolution of
Symptomatic ARIA
7. Number of Participants With
Adverse Events (AEs) and Serious Adverse Events (SAEs)
8.Change From Baseline in the
Montreal Cognitive
Assessment (MoCA) at Week
54
9.Aducanumab Concentration in
Serum
10. Number of Participants With
Antiaducanumab Antibodies in
Serum

Incidencia, intensidad, tiempo hasta la aparición y tiempo hasta la resolución de las ARIA obtenidas en las RM
Incidencia, intensidad, tiempo hasta la aparición y tiempo hasta la resolución de las ARIA sintomáticas
Incidencia de acontecimientos adversos (AA) y acontecimientos adversos graves (AAG)
Cambio desde el inicio hasta la semana 54 en la evaluación cognitiva de Montreal (Montreal Cognitive Assessment, MoCA)
Concentración de aducanumab en suero
Incidencia de anticuerpos antiaducanumab en suero

E.5.2.1

Timepoint(s) of evaluation of this end point

Secondary endpoints ;
1-7 will be Baseline up to week 54.

Secondary endpoint 8 ; baseline, week 54
Secondary endpoint 9 and 10; Pre-dose on Day 1 of
Weeks 1, 16, 24, 32, 44,
54, 56, 70, 80, 104

Del 1-7 desde la visita basal hasta la semana 54

El 8: visita basal, semana 54
El 9 y 10: Pre dosis Día 1 de la Semana 1, 16, 24, 32, 44, 54, 56, 70, 80, 104.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

Yes

E.8.2.3.1

Comparator description

Por favor mirar el Protocolo Sección 11.1.2 (0.9% cloruro sódico)

Please refer to Protocol Section 11.1.2 (0.9% sodium chloride)

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

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

Australia

Belgium

Canada

Denmark

Finland

France

Germany

Italy

Korea, Republic of

Netherlands

Poland

Portugal

Spain

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

Yes

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:

300

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

200

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

Yes

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

There maybe some patients who are incapable of giving consent personally.

Podría haber pacientes que no puedan otorgar su consentimiento personalmente.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

260

F.4.2.2

In the whole clinical trial

500

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)

No further provisions are made for access to the study treatment. If aducanumab is proven to be
beneficial, all regulatory requirements regarding poststudy access will be met.

No se preve acceso al tratamiento del estudio. Si se demotrase que aducanumab es beneficioso, se seguirían los requisitos post estudio regulatorios.

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	TrialNetworks
G.4.3.4	Network Country	United States

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2018-11-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-11-14

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2019-07-30

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