Clinical Trials Register

Summary
EudraCT Number:	2009-010922-21
Sponsor's Protocol Code Number:	B2571007(3134K1-2203-EU)
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2009-06-12
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

Germany - PEI

A.2

EudraCT number

2009-010922-21

A.3

Full title of the trial

A phase II a , Multicenter, Randomized , Third -party Unblinded , Long- term Extension study to Determine Safety, Tolerability and Immunogenicity of ACC-001 with QS-21 Adjuvant in Subjects with Mild to Moderate Alzheimer's Disease

A.3.1

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

Study in patients suffering of Alzheimer disease in order to learn whether a new compound (ACC-001 with an adjuvant) is safe, acts like a vaccine and has an effect on patient mental performance.

A.4.1

Sponsor's protocol code number

B2571007(3134K1-2203-EU)

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT00955409

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	Wyeth Pharmaceuticals Inc, a wholly owned subsidiary of Pfizer Inc, 500 Arcola Road, Collegeville, PA 19426 USA
B.1.3.4	Country	United States
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	Wyeth Pharmaceuticals Inc, a wholly owned subsidiary of Pfizer Inc, 500 Arcola Road, Collegeville, PA 19426 USA
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	Pfizer Inc
B.5.2	Functional name of contact point	Clinical Trials.gov Call Centre
B.5.3	Address:
B.5.3.1	Street Address	235 E 42nd Street
B.5.3.2	Town/ city	New York
B.5.3.3	Post code	NY 10017
B.5.3.4	Country	United States
B.5.4	Telephone number	+18007181021
B.5.5	Fax number	+18007391119
B.5.6	E-mail	ClinicalTrials.gov_Inquiries@pfizer.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	ACC-001
D.3.2	Product code	ACC-001
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	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	ACC-001 (PF-05236806)
D.3.9.3	Other descriptive name	A-Beta-1-7-CRM197 Conjugate
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
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	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)	Yes
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	ACC-001
D.3.2	Product code	ACC-001
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	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	ACC-001
D.3.9.3	Other descriptive name	A-Beta-1-7-CRM197 Conjugate
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	60
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)	Yes
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: 3
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	STIMULON
D.3.2	Product code	QS-21
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	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	STIMULON
D.3.9.1	CAS number	141256-04-04
D.3.9.2	Current sponsor code	QS-21
D.3.9.3	Other descriptive name	STIMULON
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	0.1
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)	Yes
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

Patients with mild to moderate Alzheimer's disease.

E.1.1.1

Medical condition in easily understood language

Patients with Alzheimer disease living at home or community dwelling expected to attend all study visits with a study partner able to visit him/her approximately 5 times per week

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	14.1
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

The primary objective of the study is to evaluate the long-term safety and tolerability of doses of 3, 10, and 30 µg of ACC-001 (CRM-conjugated A-beta [1-7] antigen in combination with QS-21 adjuvant) in subjects with mild to moderate AD.

E.2.2

Secondary objectives of the trial

No secondary objectives in study only Exploratory objectives:
• To assess the immunogenicity of doses of 3, 10, and 30 µg of ACC-001 in combination with QS-21.
• To assess the long-term efficacy of ACC-001 in subjects with mild to moderate AD.
• To evaluate the effect of ACC-001 on patient quality of life (QoL) and caregiver dependence and related health outcomes.
• To compare the efficacy at the end of the study between those subjects who received ACC-001 with or without QS-21 in the preceding double-blind trial and those subjects who received phosphate-buffered saline (PBS) or QS-21 in the preceding trial.
• To evaluate the change from baseline volumes for whole brain volume, brain boundary shift integral (BBSI), ventricular volume, hippocampal boundary shift integral (HBSI) and ventricular boundary shift integral (BSI) as assessed from MRI scans.
• To evaluate the change from baseline of A-beta, total tau, and phosphorylated tau (p-tau) in cerebrospinal fluid at week 78.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subjects were randomized under previous 3134K1-200-EU study and met all inclusion and none of the exclusion criteria.
2. Subject must have completed through week 78 of study 3134K1-200-EU and received at least 3 doses of investigational product and has been compliant in the opinion of the investigator and sponsor.
3. Screening brain MRI scan is consistent with the diagnosis of AD.
4. Mini-Mental State Examination (MMSE) score >=10.
5. Lives at home with appropriate caregiver capable of accompanying the subject on all clinic visits, or community dwelling with caregiver capable of accompanying the subject on all clinic visits and visiting with the subject approximately 5 times per week for the duration of the study.
6. In the opinion of the investigator, the subject and the caregiver will be compliant and have a high probability of completing the study.
7. The subject and caregiver are likely to be able to participate in all scheduled examinations and complete all required tests.

E.4

Principal exclusion criteria

1. Significant neurological disease other than AD that may affect cognition or function.
2. Early termination (ET) from the preceding 3134K1 200-EU study.
3. Experienced a SAE in the preceding double-blind study deemed related to investigational product.
4. Brain MRI evidence of vasogenic edema (VE) during the preceding 3134K1 200-EU study.
5. History of screening visit brain MRI scan indicative of any other significant abnormality including but not limited to more than 4 microhemorrhages (<10 mm), evidence of a single prior hemorrhage > 1 cm3, multiple lacunar infarcts (2 or more) or evidence of a single prior infarct > 1 cm3, evidence of a cerebral contusion, encephalomalacia, aneurysms, vascular malformations, subdural hematoma, or spaceoccupying lesions (eg, arachnoid cysts or brain tumors, such as meningioma).
6. Current clinically important systemic illness that is likely to result in deterioration of the subject’s condition or affect the subject’s safety during the study.
7. Current presence of a clinically significant major psychiatric disorder (e.g., Major Depressive Disorder) according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition-Text Revision (DSM-IV-TR), or symptom (e.g.,hallucinations, suicidal ideation, suicidal behavior), that could affect the subject's ability to complete the study.
8. Other clinically significant abnormality on screening visit which includes physical, neurological, laboratory, or electrocardiogram (ECG) examination (eg, atrial fibrillation) that could compromise the study or be detrimental to the subject.
9. Current use of clopidogrel (Plavix) and central nervous system (CNS) stimulants eg, methylphenidate [Ritalin]).
10. Presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, cerebrospinal fluid (CSF) shunts, or metal fragments or foreign objects in the eyes, skin, or body, or claustrophobia that would contraindicate a brain MRI scan.

E.5 End points

E.5.1

Primary end point(s)

Safety assessments will include vital sign measurements, weight, physical and neurological examinations, 12-lead ECG recordings, and brain MRI scans (at screening and before each immunization and at the end of the study), including T2*/gradient echo MRI). Clinical laboratory evaluations will include complete blood count (CBC) with platelet count, chemistry panel, and urinalysis, thyroid panel, serum vitamin B12 and folate, coagulation studies, and circulating immune complexes and anti-A-beta titers.

E.5.1.1

Timepoint(s) of evaluation of this end point

At every study visit

E.5.2

Secondary end point(s)

No secondary endpoints in study - exporataory endpoints are:
To assess the immunogenicity of doses of 3, 10, and 30 ug of ACC-001 (CRM-conjugated A-beta [1-7] antigen in combination with QS-21 adjuvant) in subjects with mild to moderate AD. Change from baseline levels of anti-A-beta IgG at week 0, 4, 12, 24, 30, 36, 50, 56, 66, 76, 82, and 104. baseline is defined as level prior to first treatment with ACC-001 with QS 21. Anti-A-beta IgM and IgG subclass antibody levels may be assessed at selected time points.
 To assess the long-term efficacy of ACC-001 in subjects with mild to moderate AD utilizing Alzheimer disease assessment scale-cognitive (ADAS-Cog), mini-mental state examination (MMSE), neuropsychiatric test battery (NTB), disability assessment for dementia (DAD), neuropsychiatric inventory (NPI), and clinical dementia rating-sum of boxes (CDR-SOB) at week 0, 26, 52, 78, and 104.
 To evaluate the health outcomes of times spent caregiving and resource utilization (Resource Use Dementia [RUD-lite]), quality of life in patients with AD [QoL-AD], and Dependence Scale (DS) at week 0, 26, 52, 78, and 104 To compare the efficacy at the end of the study between those subjects who received ACC-001in the preceding double-blind trial and those subjects who received placebo (phosphate-buffered saline [PBS] or QS-21) in the preceding trial.
 To evaluate the change from baseline volumes for whole brain volume, brain boundary shift integral (BBSI), hippocampal boundary shift integral (HBSI), ventricular volume, and ventricular boundary shift integral (VBSI) as assessed from MRI scans, at month 24 –(week 104).
 To evaluate the change from baseline of A-beta, total tau, and phosphorylated tau (p-tau) in cerebrospinal fluid at week 78.

E.5.2.1

Timepoint(s) of evaluation of this end point

At various timepoint between Day 1 and Week 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

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

ACC-001 + adjuvant (QS-21)

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

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

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

Last visit of the last subject.

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:

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

Yes

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Alzheimer's disease patients may need a legal representative signature.

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

120

F.4.2.2

In the whole clinical trial

120

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)

Subjects can maintain basic therapy with cholinesterase inhibitors and/or memantine throughout their participation in the trial. The standard of care therapy at the study site will be provided after the patient's participation has ended.

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

2009-09-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-08-27

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-12-17

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