Clinical Trials Register

Summary
EudraCT Number:	2012-000943-29
Sponsor's Protocol Code Number:	BP28248
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-10-22
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

Poland - Office for Medicinal Products

A.2

EudraCT number

2012-000943-29

A.3

Full title of the trial

A PHASE II, MULTICENTER, RANDOMIZED, DOUBLE-BLIND,
PARALLEL-GROUP, PLACEBO-CONTROLLED STUDY TO
INVESTIGATE THE EFFICACY AND SAFETY OF RO4602522
ADDED TO BACKGROUND ALZHEIMER'S DISEASE THERAPY IN
PATIENTS WITH MODERATE SEVERITY ALZHEIMER'S DISEASE

A.3.1

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

A GLOBAL CLINICAL STUDY TO INVESTIGATE THE EFFECTIVENESS AND SAFETY OF RO4602522 WHEN TAKEN IN ADDITION TO ALZHEIMER'S DISEASE THERAPY IN PATIENTS WITH MODERATE ALZHEIMER'S DISEASE

A.4.1

Sponsor's protocol code number

BP28248

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01677754

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	F. Hoffmann-La Roche Ltd
B.1.3.4	Country	Switzerland
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	F. Hoffmann-La Roche Ltd
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	F.Hoffmann-La Roche Ltd
B.5.2	Functional name of contact point	Trial Information Support Line-TISL
B.5.3	Address:
B.5.3.1	Street Address	Grenzacherstrasse 12
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4070
B.5.3.4	Country	Switzerland
B.5.6	E-mail	global.rochegenentechtrials@roche.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	MAO-B Inhibitor
D.3.2	Product code	Ro 460-2522/F02
D.3.4	Pharmaceutical form	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.3.9.1	CAS number	676479-06-4
D.3.9.2	Current sponsor code	RO4602522
D.3.9.3	Other descriptive name	MAO-B inhibitor
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	0.5
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	MAO-B Inhibitor
D.3.2	Product code	Ro 460-2522/F03
D.3.4	Pharmaceutical form	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.3.9.1	CAS number	676479-06-4
D.3.9.2	Current sponsor code	RO4602522
D.3.9.3	Other descriptive name	MAO-B inhibitor
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	2.5
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.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	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

The most common form of dementia, i.e. the serious loss of global cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging

E.1.1.2

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.0
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

• To evaluate the efficacy of a 12-month treatment of RO4602522 versus placebo added to AChEI alone or in combination with memantine in patients with moderate severity AD (MMSE 13-20 inclusive), based on mean change in ADAS-Cog-11 scores (cognitive endpoint) from baseline over time.

E.2.2

Secondary objectives of the trial

• Effect on cognition assessed with the ADAS-Cog-11 scale
• Effect on functioning assessed with the ADCS-ADL scale
• Effect on behavioral symptoms
• Effect on the global measures assessed with the ADCS-CGIC scale and the Global Deterioration Scale (GDS).
• Assessment of safety and tolerability
• Estimating population-PK parameters and investigating the influence of various covariates on these parameters.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Probable AD, based on the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS)/Alzheimer’s Disease and Related Disorders Association (ADRDA) and DSM-IV-TR criteria.
2. 50-90 years of age
3.MMSE score at screening between 13 and 20, inclusive
4. MRI supports a diagnosis of AD, with no evidence of other disease likely to account for the subject’s dementia.
5. Body mass index (BMI) between 18 and 36.
6. Modified Hachinski Ischemia Score of ≤4.
7. Patients with CSDD scores ≤13.
8. Receiving treatment with donepezil, rivastigmine, galantamine or any of these AChEIs in combination with memantine for at least 4 months,, with their dose and formulation stabilized at least 3 months prior to screening. All formulation and dosages are allowed except donezepil 23 mg (alone or in combination).
9. Generally healthy and ambulatory or ambulatory-aided (i.e., walker or cane).
10. Have a caregiver who has frequent contact with the patient, who is considered reliable, who can accompany patient to study visits and help with protocol procedures, and who is also able and willing to provide input for completing the caregiver scales and sign the caregiver consent form.
11. Females of childbearing potential must have a negative pregnancy test and must agree to use effective contraception

E.4

Principal exclusion criteria

1. Any neurological or psychiatric condition that may currently or during the course of the study impair cognition or functioning that is not associated with Alzheimer's disease
2. Background of mental retardation
3. At risk of suicide
4. Uncontrolled behavioral symptoms
5. Alcohol and/or substance abuse or dependence in the past 2 years, except nicotine use
6. Preexisting neuropathy
7. Unstable or poorly controlled hypertension and/or cardiovascular disease
8. Clinically relevant ECG abnormality
9. Bradycardia
10. Aspartate aminotransferase, alanine aminotransferase or total bilirubin ≥1.5 times the upper limit of normal
11. HIV positive, history of Hepatitis B infection within the past year, or history of Hepatitis C infection
12. Hepatitis B virus surface Antigen (HBsAg) and/or Hepatitis C antibodies (HepCAb) positive
13. Abnormal thyroid function tests
14. Poorly controlled diabetes
15. Severe renal impairment
16. Requiring nursing home care. Patients living in assisted living
facilities are allowed if a reliable caregiver is available (see inclusion
criteria)
17. History of cancer except if considered likely to be cured as
documented by an oncologist / surgeon or in the case of non-melanoma skin cancers and prostate adenocarcinoma if there has been no significant progression over the last 2 years
18. Involvement in any other investigational trial in the last 3 months
19. Current treatment for AD other than those listed in inclusion criteria
20. Participation at any time in an active AD vaccine study
21. Participation in a passive AD immunization study less than 1 year before screening, with exceptions as per protocol
22. Recent (≤ 12 weeks) use of MAO inhibitors
23. Antidepressant treatment recently initiated (≤ 6 weeks).
24. Psychotropic medication as defined by protocol
25. Unwilling/ Unable to avoid ingesting food with high tyramine content (yeast concentrate, soy sauce, aged overripe cheese or very salty food)

E.5 End points

E.5.1

Primary end point(s)

The change from baseline in ADAS-Cog-11 over 12 months.

E.5.1.1

Timepoint(s) of evaluation of this end point

following 12-month treatment (compared to baseline)

E.5.2

Secondary end point(s)

Mean ADCS-CGIC score, the mean change from baseline over time in ADCS-ADL, BEHAVE-AD-FW, AES and GDS scores, and the proportion of
patients worsening over time in BEHAVE-AD-FW and ADCS-CGIC scores.

E.5.2.1

Timepoint(s) of evaluation of this end point

following 12-month treatment (compared to baseline)

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

Yes

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

Yes

E.6.13.1

Other scope of the trial description

Tolerability

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

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

Canada

United States

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

The end of the study will be considered to be the date of the last patient’s last visit (LPLV), including the last follow-up visit.

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:

124

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

371

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

For subjects incapable of providing informed consent due to reduced
decision-making capacity, this should be provided by the patient's legal representative appointed by the court and by the closest relatives, as required by the national law.

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

248

F.4.2.2

In the whole clinical trial

495

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)

The study drug RO4602522 is for experimental use only and it will not yet be approved for use at the time of the completion of this study. There are other therapies available to treat Alzheimer’s Disease. There are no plans for continued treatment with RO4602522 or medical supervision of the patients after the end of the trial. Decisions concerning the care of the patient will be left with the patients’ treating physician after completion of the trial.

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

2012-12-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-09-12

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-06-03

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