A phase II a , Multicenter, Randomized , Third -party Unblinded , Long- term Extension study to Determine Safety, Tolerability and Immunogenicity of ACC-001 with and without QS21 Adjuvant in Subjects with Mild to Moderate Alzheimzer's Disease ?Estudio de fase IIa, multicéntrico, aleatorizado y con tercera parte conocedora del tratamiento, de extensión a largo plazo, para determinar la seguridad, la tolerabilidad y la inmunogenicidad de ACC-001, con y sin adyuvante QS-21, en sujetos con enfermedad de Alzheimer de grado leve a moderado"

• Register: EUCTR
• Last refreshed on: 10 March 2014
• Main ID: EUCTR2009-010922-21-ES
• Date of registration: 13/07/2009
• Prospective Registration: Yes
• Primary sponsor: Wyeth Pharmaceuticals France, Wyeth Research Division
• Public title: A phase II a , Multicenter, Randomized , Third -party Unblinded , Long- term Extension study to Determine Safety, Tolerability and Immunogenicity of ACC-001 with and without QS21 Adjuvant in Subjects with Mild to Moderate Alzheimzer's Disease ?Estudio de fase IIa, multicéntrico, aleatorizado y con tercera parte conocedora del tratamiento, de extensión a largo plazo, para determinar la seguridad, la tolerabilidad y la inmunogenicidad de ACC-001, con y sin adyuvante QS-21, en sujetos con enfermedad de Alzheimer de grado leve a moderado"
• Scientific title: A phase II a , Multicenter, Randomized , Third -party Unblinded , Long- term Extension study to Determine Safety, Tolerability and Immunogenicity of ACC-001 with and without QS21 Adjuvant in Subjects with Mild to Moderate Alzheimzer's Disease ?Estudio de fase IIa, multicéntrico, aleatorizado y con tercera parte conocedora del tratamiento, de extensión a largo plazo, para determinar la seguridad, la tolerabilidad y la inmunogenicidad de ACC-001, con y sin adyuvante QS-21, en sujetos con enfermedad de Alzheimer de grado leve a moderado"
• Date of first enrolment: 23/10/2009
• Target sample size: 64
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-010922-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: yes Other trial design description: ... If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: No comparator or placebo arm in study; IMP (ACC-001) is administered alone or with adjuvant (QS-21)

Countries of recruitment

France, Germany, Spain

Key inclusion & exclusion criteria

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.
Are the trial subjects under 18? no
Number of subjects for this age range:
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

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 multiple microhemorrhages (2 or more), 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 space-occupying 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. 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.
8. 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with mild to moderate Alzheimer's disease. Enfermedad de Alzheimer.

Intervention(s)

Product Name: ACC-001
Product Code: ACC-001
Pharmaceutical Form: Injection*
Current Sponsor code: ACC-001
Other descriptive name: A-Beta-1-7-CRM197 Conjugate
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 25-

Product Name: ACC-001
Product Code: ACC-001
Pharmaceutical Form: Injection*
Current Sponsor code: ACC-001
Other descriptive name: A-Beta-1-7-CRM197 Conjugate
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 60-

Product Name: ACC-001 + QS-21 Adjuvant
Product Code: ACC-001 + QS-21 Adjuvant
Pharmaceutical Form: Injection*
Current Sponsor code: ACC-001
Other descriptive name: A-Beta-1-7-CRM197 Conjugate
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 25-

Product Name: ACC-001 + QS-21 Adjuvant
Product Code: ACC-001 + QS-21 Adjuvant
Pharmaceutical Form: Injection*
Current Sponsor code: ACC-001
Other descriptive name: A-Beta-1-7-CRM197 Conjugate
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 60-

Primary Outcome(s)

Secondary Objective: ? To assess the immunogenicity of doses of 3, 10, and 30 µg of ACC-001
? 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, and ventricular boundary shift integral (BSI) as assessed from MRI scans.

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.

Main Objective: 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 alone and in combination with QS-21 adjuvant) in subjects with mild to moderate AD.

Secondary ID(s)

3134K1-2203-EU

2009-010922-21-DE