Clinical Trials Register

Summary
EudraCT Number:	2015-000948-42
Sponsor's Protocol Code Number:	54861911ALZ2003
National Competent Authority:	Sweden - MPA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2015-08-14
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

Sweden - MPA

A.2

EudraCT number

2015-000948-42

A.3

Full title of the trial

A Phase 2b/3 Randomized, Double-blind, Placebo-Controlled, Parallel Group, Multicenter Study Investigating the Efficacy and Safety of JNJ-54861911 in Subjects who are Asymptomatic At Risk for Developing Alzheimer’s Dementia

A.3.1

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

Efficacy and Safety Trial of JNJ-54861911 in Participants who are Asymptomatic At Risk for Developing Alzheimer’s Dementia

A.4.1

Sponsor's protocol code number

54861911ALZ2003

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	Janssen-Cilag International N.V.
B.1.3.4	Country	Belgium
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	Janssen Research and Development, LLC
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	Janssen Pharmaceutica N.V.
B.5.2	Functional name of contact point	Clinical Registry Group
B.5.3	Address:
B.5.3.1	Street Address	Archimedesweg 29
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	2333 CM
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	31071524 2166
B.5.5	Fax number	31071524 2110
B.5.6	E-mail	ClinicalTrialsEU@its.jnj.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	JNJ-54861911
D.3.2	Product code	JNJ-54861911
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Atabecestat
D.3.9.1	CAS number	1200493-78-2
D.3.9.2	Current sponsor code	JNJ-54861911
D.3.9.3	Other descriptive name	JNJ-54861911-AAA
D.3.9.4	EV Substance Code	SUB107735
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
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	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	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	JNJ-54861911
D.3.2	Product code	JNJ-54861911
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Atabecestat
D.3.9.1	CAS number	1200493-78-2
D.3.9.2	Current sponsor code	JNJ-54861911
D.3.9.3	Other descriptive name	JNJ-54861911-AAA
D.3.9.4	EV Substance Code	SUB107735
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
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	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	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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

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

E.1.1.1

Medical condition in easily understood language

Alzheimer's Disease (AD) is a neurodegenerative disease associated with aging. AD patients suffer from cognition deficits and memory loss as well as behavioral problems such as anxiety.

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 this study is to determine whether treatment with JNJ-54861911 slows cognitive decline compared with placebo treatment, as measured by a composite cognitive measure, the Preclinical Alzheimer Cognitive Composite (PACC), in amyloid-positive subjects who are asymptomatic at risk for developing Alzheimer's dementia.

E.2.2

Secondary objectives of the trial

- Change from Baseline in Cognitive Function Index (CFI) to Month 54
- Change from Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living - Prevention Instrument (ADCS-ADL-PI) Total Score to Month 54
- Change from Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Scale Score to Month 51
- Change from Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) Score to Month 54
- Change from Baseline in Neuropsychological Assessment Battery Daily Living Tests (NAB-DLTs) Score to Month 54
- Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
- Trough Plasma Concentration (Ctrough) of JNJ54861911
- Area Under the Plasma Concentration Time Curve from 0 to tau Hours After Dosing (AUCtau)
- Change in mean Cerebral Fibrillar Amyloid Accumulation
- Change from Baseline of Neurodegeneration by Assessing Changes in imaging Biomarkers

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 and Objective: Characterization of T-cell Response in Subjects Previously Treated with JNJ-54861911
Date and Version: 19 Dec 2017 version 1

E.3

Principal inclusion criteria

1. Subject must be a man or woman 60 to 85 years of age, inclusive, at time of informed consent. Subjects 60 to 64 years of age must also have 1 of the following 3 conditions:
a. A positive family history for dementia (minimum of 1 first degree relative)
b. A previously known APOE ɛ4 genotype
c. A previously known biomarker status demonstrating elevated amyloid accumulation in CSF or PET
2. Subjects must have a global CDR score of 0 at screening.
3. Subjects must be able to read and write and must have adequate hearing and visual acuity to complete the psychometric tests. The legally acceptable representative must also be able to read and write.
4. Subjects must have evidence of elevated amyloid accumulation by means of either:
a. Low CSF Aβ1-42 levels at screening
b. A positive amyloid PET scan at screening (depending on the site’s PET capability)

Note: The cut off value for CSF Aβ1-42 will be based on the value established by the central CSF screening laboratory and specified in a separate laboratory manual. Screening amyloid PET scans will be assessed centrally by a qualified reader for inclusion based on predefined criteria as documented in the imaging manual.

E.4

Principal exclusion criteria

1. Subject is receiving an acetylcholinesterase (AChE) inhibitor and/or memantine at any time during screening or Day 1 predose.
2. Subject has evidence of any brain disease other than potential very early signs of AD (eg, mild hippocampal atrophy) or typical age-related changes (eg, mild white matter hyperintensity on MRI). The screening MRI scan shall be interpreted by a local radiologist and a central radiologist for exclusionary findings prior to enrolling the subject. Both local and central interpretations shall be reviewed by the investigator; in case of disagreement, the central radiology report will be used to determine subject eligibility in consultation with the sponsor’s medical monitor.
3. Subject has any other abnormality that could cause a possible cognitive deficit (including, but not limited to vascular encephalopathy or large strokes [as imaged by cerebral MRI]).
4. Subject has any contraindications for MRI (eg, prostheses, implants, claustrophobia, pacemaker)
5. Subject has met criteria for dementia or has a brain disorder that can cause dementia.
6. Subject has evidence of familial autosomal dominant AD (mutation identified in the family and/or subject prior to randomization).
7. Subject has a history of or current thyroid disease or thyroid dysfunction, which is currently uncontrolled, unevaluated, or untreated. Subjects treated for thyroid disease may be enrolled following review of their diagnostic and treatment history records by the investigator and with written concurrence by the sponsor's medical monitor to ensure disease/treatment stability and compliance.
8. Subject has a vitamin B12 or folic acid deficiency. A low vitamin B12 level is exclusionary unless follow-up labs (homocysteine and methylmalonic acid) indicate that the value is not physiologically significant. Subjects treated with vitamin B12 or folic acid may be enrolled following review of their diagnostic and treatment history records by the investigator and with written concurrence by the sponsor's medical monitor to ensure disease/treatment stability and compliance.
9. Subject has chromosome 21 trisomy (Down syndrome).
10. Subject has a history within the past 2 years or current diagnosis of significant psychiatric illness, per the most current version of the Diagnostic and Statistical Manual of Mental Disorders (DSM) (including but not limited to major depressive disorders and anxiety disorders) (subjects who are symptom free or with minimal limited symptoms may be included); or the subject has a current diagnosis or history of schizophrenia or bipolar disorder.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is the change in the PACC score from baseline.

E.5.1.1

Timepoint(s) of evaluation of this end point

54 months

E.5.2

Secondary end point(s)

• Change from baseline at Month 54 on CFI (total score)
• Change from baseline at Month 54 in ADCS-ADL-PI score (total score)
• Change from baseline at Month 51 on RBANS (total scale score)
• Change from baseline at Month 54 on CDR-SB
• Change from baseline at Month 54 on NAB-DLTs for Memory and Attention

E.5.2.1

Timepoint(s) of evaluation of this end point

54 months for all endpoints except RBANS (51 months)

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

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

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)

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

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

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

Denmark

Finland

Germany

Italy

Japan

Mexico

Netherlands

Spain

Sweden

Switzerland

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

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:

1400

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

631

F.4.2.2

In the whole clinical trial

1650

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)

Expected normal treatment

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

2015-08-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-12-14

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

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