Clinical Trials Register

Summary
EudraCT Number:	2016-000108-27
Sponsor's Protocol Code Number:	H8A-MC-LZBE
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:	2016-09-26
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2016-000108-27

A.3

Full title of the trial

A 24-Month, Phase 3, Multicenter, Placebo-Controlled Study
of Efficacy and Safety of Solanezumab versus Placebo in
Prodromal Alzheimer’s Disease

Estudio de fase 3, multicéntrico, comparativo con placebo, de 24 meses de duración, en el que se evalúan la eficacia y la seguridad de solanezumab en comparación con el placebo, en pacientes con enfermedad de Alzheimer en fase prodrómica

A.3.1

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

This is a Phase 3 study designed to test whether drug product will slow disease progression in patients with mild memory problems (prodromal Alzheimer's disease).

Estudio fase 3 destinado a probar si el fármaco frena la progresión de la enfermedad en pacientes con problemas de memoria leves (enfermedad de Alzheimer prodromica).

A.3.2

Name or abbreviated title of the trial where available

A Study of Solanezumab (LY2062430) in Participants With Prodromal Alzheimer's Disease (ExpeditionPRO

Estudio con Solanezumab (LY2062430) en pacientes con engermedaad de Alzheimer prodromica

A.4.1

Sponsor's protocol code number

H8A-MC-LZBE

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	Lilly S.A.
B.1.3.4	Country	Spain
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	Eli Lilly and Company
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Lilly
B.5.2	Functional name of contact point	Site Actiation
B.5.3	Address:
B.5.3.1	Street Address	Avda de la Industria 30
B.5.3.2	Town/ city	Alcobendas
B.5.3.3	Post code	28108
B.5.3.4	Country	Spain
B.5.4	Telephone number	34916635327
B.5.5	Fax number	34916633481
B.5.6	E-mail	ensayosclinicos@lilly.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	solanezumab
D.3.2	Product code	LY2062430
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	N/A
D.3.9.1	CAS number	955085-14-0
D.3.9.2	Current sponsor code	LY2062430
D.3.9.3	Other descriptive name	SOLANEZUMAB
D.3.9.4	EV Substance Code	SUB37126
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	20
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	No

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	Concentrate for solution for 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

Prodromal Alzheimer’s Disease

Enfermedad de Alzheimer en fase prodrómica

E.1.1.1

Medical condition in easily understood language

Medical condition in which an individual's memory, thinking, judgment, and gradually their ability to function is lost.

Enfermedad en la que la persona pierde la memoria, la capacidad de pensar, el sentido de la realidad y, de forma gradual, la capacidad funcional.

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	19.0
E.1.2	Level	PT
E.1.2	Classification code	10012271
E.1.2	Term	Dementia Alzheimer's type
E.1.2	System Organ Class	10029205 - Nervous system disorders

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 assess the hypothesis that solanezumab 400 mg
Q4W will slow the clinical progression of prodromal
AD over 24 months compared to placebo

Evaluar la hipótesis de que la administración de 400 mg de solanezumab C4S durante 24 meses ralentizará la progresión clínica de la fase prodrómica de la EA, en comparación con el placebo.

E.2.2

Secondary objectives of the trial

To assess the effect of solanezumab vs. placebo on the clinical
progression of prodromal AD over 24 months
To assess the effect of solanezumab vs. placebo on quality of life and
health outcomes in prodromal AD over 24 months
To assess the effect of solanezumab vs. placebo on biomarkers in
prodromal AD over 24 months
To assess the hypothesis that change from baseline in accumulation of
tau pathology over 12 and 24 months is associated with changes from
baseline in cognition

• Evaluar el efecto de solanezumab sobre la progresión clínica en la fase prodrómica de la EA al cabo de 24 meses, en comparación con el placebo.
• Evaluar el efecto de solanezumab sobre la calidad de la vida y los resultados de salud en la fase prodrómica de la EA al cabo de 24 meses, en comparación con el placebo.
• Evaluar el efecto de solanezumab sobre los biomarcadores en la fase prodrómica de la EA al cabo de 24 meses, en comparación con el placebo.
• Evaluar la hipótesis de que la variación al cabo de 12 y 24 meses respecto al período basal en la acumulación patológica de proteína tau se asocia con variaciones en la función cognitiva respecto al período basal.

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

Protocol Addendum H8A-MC-LZBE(1)
(18F-AV-1451 tau imaging)
A 24-Month, Phase 3, Multicenter, Placebo-Controlled
Study of Efficacy and Safety of Solanezumab versus
Placebo in Prodromal Alzheimer’s Disease. 28Mar2016. Objectives: To assess the hypothesis that solanezumab will slow
the accumulation of tau pathology over 12 and 24
months compared to placebo; To assess the hypothesis that change from baseline in
accumulation of tau pathology over 12 and 24
months is associated with changes from baseline in
cognition; and To assess the hypothesis that change from baseline in
accumulation of tau pathology over 24 months is
associated with changes from baseline in function.

Protocol Addendum H8A-MC-LZBE(2) (LP)
A 24-Month, Phase 3, Multicenter, Placebo-Controlled
Study of Efficacy and Safety of Solanezumab versus
Placebo in Prodromal Alzheimer’s Disease. 28Mar2016. Objectives: Lumbar punctures (LPs) will be used to collect cerebrospinal fluid (CSF) for assays of
solanezumab, amyloid beta (AB) species, and tau proteins (as described in this addendum); and
for CSF storage.

Adenda al protocolo H8A-MC-LZBE(1)
(Pruebas de imagen con 18F-AV-1451 para determinar la acumulación de proteína tau)
Estudio de fase 3, multicéntrico, comparativo con placebo, de 24 meses de duración, en el que se evalúan la eficacia y la seguridad de solanezumab en comparación con el placebo, en pacientes con enfermedad de Alzheimer en fase prodrómica 28Mar2016. Objetivos: Evaluar la hipótesis de que solanezumab ralentizará la acumulación patológica de proteína tau al cabo de 12 y 24 meses, en comparación con el placebo; evaluar la hipótesis de que la variación al cabo de 12 y 24 meses respecto al período basal en la acumulación patológica de proteína tau se asocia con variaciones en la función cognitiva respecto al período basal; y evaluar la hipótesis de que la variación al cabo de 24 meses respecto al período basal en la acumulación patológica de proteína tau se asocia con variaciones en la función respecto al período basal.

Adenda al protocolo H8A-MC-LZBE(2) (PL)
Estudio de fase 3, multicéntrico, comparativo con placebo, de 24 meses de duración, en el que se evalúan la eficacia y la seguridad de solanezumab en comparación con el placebo, en pacientes con enfermedad de Alzheimer en fase prodrómica 28Mar2016. Objetivos:
Se realizarán punciones lumbares (PL) con el fin de obtener líquido cefalorraquídeo (LCR) para su conservación y para realizar análisis de solanezumab, las especies de beta amiloide (BA) y las proteínas tau (según se describe en esta adenda).

E.3

Principal inclusion criteria

•Has a diagnosis by the study investigator of a clinical syndrome of
cognitive impairment consistent with prodromal AD per International
Working Group (IWG) diagnostic criteria or MCI due to AD per National
Institute on Aging-Alzheimer's Association (NIA-AA) diagnostic criteria.
•Has evidence of amyloid pathology by PET imaging or lumbar puncture CSF
•Scores 17-28 on MoCA at screening.
•Scores <27 on free recall cutoff score from the FCSRT (Picture
version) at screening.
•Scores ≤4 on Modified Hachinski Ischemia Scale (MHIS).
•Scores >0 on the FAQ.
•Has a florbetapir PET scan or CSF result at screening consistent with
the presence of amyloid pathology.

• Diagnóstico por parte del investigador del estudio de un síndrome clínico de deterioro cognitivo que concuerde con la presencia de EA en la fase prodrómica, de acuerdo con los criterios diagnósticos del International Working Group (IWG), o de un deterioro cognitivo leve (DCL) debido a la EA, de acuerdo con los criterios diagnósticos de la National Institute on Aging-Alzheimer's Association (NIA-AA).
• Signos de depósitos patológicos de péptidos amiloides, de acuerdo con la PET o con el análisis del LCR obtenido mediante punción lumbar.
• Puntuación de entre 17 y 28 en la evaluación cognitiva de Montreal (MoCA) durante la selección.
• Puntuación de corte del recuerdo libre < 27 en la prueba de recuerdo libre/facilitado (FCSRT) (versión gráfica) durante la selección.
• Puntuación ≤ 4 en la escala modificada de isquemia de Hachinski (MHIS).
• Puntuación > 0 en el cuestionario de actividades funcionales (FAQ).
• Presencia de depósitos patológicos de péptidos amiloides de acuerdo con la PET con florbetapir o con el análisis del LCR llevados a cabo durante la selección.

E.4

Principal exclusion criteria

•Has had MRI or computerized tomography (CT) of brain within previous
2 years showing pathology that would be inconsistent with a diagnosis
of AD.
•Has known allergy to humanized monoclonal antibodies.
•Has an ongoing clinically significant laboratory abnormality, as
determined by the investigator.
•Has screening MRI with results showing >4 amyloid related imaging
abnormalities H (ARIA-H) micro-hemorrhages or presence of ARIA-E.
•Has any contraindications for MRI studies, including claustrophobia, the
presence of metal (ferromagnetic) implants, or a cardiac pacemaker that
is not compatible with MRI.
•Has received treatment with a stable dose of an achetylcholinesterase
(AChEI)inhibitor or memantine for less than 2 months before
randomization. (If a participant has recently stopped AChEIs and/or
memantine, he or she must have discontinued treatment at least 2
months before randomization.)

• Presentar alguna enfermedad (de acuerdo con los resultados de una RMN o de una tomografía axial computarizada [TAC] del cerebro que se haya realizado en el transcurso de los 2 años anteriores), que no concuerde con un diagnóstico de EA.
• Alergia a los anticuerpos monoclonales humanizados
• Presentar en la actualidad una alteración analítica clínicamente significativa, de acuerdo con el criterio del investigador.
• Presentar en una RMN realizada durante la selección > 4 microhemorragias amiláceas (depósitos patológicos de hemosiderina en la prueba diagnóstica de imagen [ARIA-H]) o presencia de ARIA-E.
• Presentar cualquier contraindicación para la realización de RMN, entre otras, claustrofobia, presencia de implantes metálicos (ferromagnéticos) o de un marcapasos que imposibilite la RMN.
• Haber recibido antes de la aleatorización tratamiento con una dosis estable de un inhibidor de la acetilcolinesterasa (AChEI) o memantina durante un período inferior a 2 meses. (Si un participante ha interrumpido recientemente el tratamiento con un AChEI o con memantina, dicha interrupción definitiva deberá haberse producido al menos 2 meses antes de la aleatorización).

E.5 End points

E.5.1

Primary end point(s)

Alzheimer´s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog14) Score

Puntuación de la Escala de evaluación de la enfermedad de Alzheimer - Subescala cognitiva -ADASCog14

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline, 24 months

Período basal, 24 meses.

E.5.2

Secondary end point(s)

Alzheimer´s Disease Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCIADL); Mini Mental Status Examination (MMSE); Montreal Cognitive Assessment (MoCA); Functional Activities Questionnaire (FAQ); Neuropsychiatric Inventory (NPI); Clinical Dementia Rating Scale Sum of Boxes (CDR-SB); Repeatable Battery for the Assessment of Neuropsychological Status (RBANS); Free and Cued Selective Reminding Test
(FCSRT); Resource Utilization in Dementia-Lite (RUD-Lite); EuroQol 5-Dimensional Health-Related Quality of Life Scale (EQ-5D); Quality of Life in Alzheimer's Disease Scale (QoL-AD); Concentration of Plasma Amyloid-β Peptide (Aβ) and Plasma Solanezumab; Volumetric Magnetic Resonance Imaging (vMRI); Florbetapir Positron Emission Tomography (PET) Standardized Uptake Value Ratio (SUVr); Concentration of Cerebrospinal Fluid (CSF) Aβ and CSF Tau Proteins; Pharmacogenomics Markers

Escala “Estudio cooperativo de la enfermedad de Alzheimer – Actividades cotidianas, deterioro cognitivo leve” (ADCS-MCI-ADL); Miniexamen Cognoscitivo (MMSE); Evaluación cognitiva de Montreal (MoCA); Cuestionario sobre las actividades funcionales (FAQ); Inventario neuropsiquiátrico (NPI); Escala de valoración clínica de la demencia, suma de casillas (CDR-SB); Batería repetible para la evaluación del estado neuropsicológico (RBANS); Prueba de recuerdo libre/facilitado (FCSRTT); Escala “Utilización de recursos en la demencia - Lite” (RUD-Lite); Escala de calidad de vida relacionada con la salud de 5 dimensiones EuroQol (EQ-5D); Escala de calidad de vida en la enfermedad de Alzheimer (QoL-AD); Concentración plasmática de péptidos β-amiloide (βA) y concentración plasmática de solanezumab; Resonancia magnética nuclear volumétrica (RMNv); Razón de captación normalizada (RCn) en la tomografía por emisión de positrones (PET) con florbetapir; Concentración de péptidos β-amiloide (βA) en el líquido cefalorraquídeo (LCR) y concentración de proteínas tau en el LCR; Marcadores farmacogenómicos.

E.5.2.1

Timepoint(s) of evaluation of this end point

Baseline, 24 months

Período basal, 24 meses.

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

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

Yes

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)

Yes

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

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

Yes

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

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

China

Finland

France

Germany

Italy

Japan

Korea, Democratic People's Republic of

Netherlands

Poland

Spain

Sweden

Switzerland

Taiwan

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

Ultima visita ultimo pacinete

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:

1225

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

1225

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

Those with rapid disease progression making later reconsents an issue. All will be able to consent at entry into the trial, but a rapid decline in cognition (which would be unexpected in this population) might be a risk.

Pacientes que presenten rápida progresión de la enfermedad, puede dificultar su consentimiento en adelante. Los pacientes que otorgen su consentimiento pueden experimentar un deterioro cognitivo (no se prevé que sea el caso) podría ser un riesgo.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

120

F.4.2

For a multinational trial

F.4.2.1

In the EEA

828

F.4.2.2

In the whole clinical trial

1622

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

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2016-10-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-10-18

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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