E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with mild degree of Alzheimer's Disease |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001896 |
E.1.2 | Term | Alzheimer's disease |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to assess the clinical activity based on assessment of cognitive and functional domains of repeated immunizations of AD patients in an early stage with AFFITOPE AD02. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objective is to assess immunological activity, the overall clinical activity, the impact on health-related quality of life, the treatment effect on the biomarker brain atrophy as well as the safety and tolerability of the Alzheimer AFFITOPE AD02 vaccine. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Confirmed diagnosis of probable & mild Alzheimer’s disease -Diagnosis of probable Alzheimer’s disease based on the NINCDS/ADRDA criteria. -Assessing the severity of Alzheimer’s disease of mild degree by the Mini Mental State Examination (MMSE). AD of mild degree has been confirmed if the MMSE score is ≥20. -Hachinski Ischemia Scale is used to distinguish AD from vascular dementia. A score of ≤ 4 suggests AD. -The result of the Magnetic Resonance Imaging scan (MRI) of the patient’s brain has to be consistent with the diagnosis of AD, central reading. This includes medial temporal lobe atrophy as assessed by the Scheltens scale. Further conditions for inclusion into the clinical trial -Written informed consent signed and dated by the patient and the caregiver. The patient’s capability to give informed consent has to be confirmed by an independent professional. -Deterioration in the patient’s episodic memory test (according to Dubois and colleagues; cut-off: total recall: <40, cued recall: <17). -Age between 50 and 80 years. -Availability of a partner/caregiver knowing the patient and being able to accompany the patient at the visits and being available for the telephone interviews. -Adequate visual and auditory acuity to allow neuropsychological testing. -Female patients of childbearing potential are eligible if they use a medically accepted contraceptive method. -Availability of the APOE genotype. -A potential participant treated with conventional AD and hypothyreoidism therapies must be on stable doses for at least 3 months prior to Visit 1 and during the entire trial period. -A potential participant has to be on stable doses of all medications he/she is taking because of consisting illnesses according to medical history (except AD and hypothyreoidism therapies, AD therapies will be recorded separately) for at least 30 days prior to Visit 1. |
|
E.4 | Principal exclusion criteria |
-Pregnant women. -Sexually active women of childbearing potential who are not using a medically accepted birth control method. -Participation in another clinical trial within 3 months before Visit 1. -History of questionable compliance to visit schedule; patients not expected to complete the clinical trial. -Presence or history of allergy to components of the vaccine, if considered relevant by the investigator. -Contraindication for MRI imaging, including but not limited to pacemakers; cochlear implants, cerebral aneurysm clips; implanted infusion pumps; implanted nerve stimulators; metallic splinters in the eye; other magnetic, electronic, or mechanical implants; or any other clinical history or examination finding that, in the judgement of the investigator, would pose a potential hazard in combination with MRI. -Inability to tolerate MRI procedure (e.g., claustrophobia, inability to lie motionless for 30 minutes, noise sensitivity). -MRI findings at Visit 1 excluding participation: a significant number of microhemorrhages, a single prior hemorrhage > 1 cm3, 2 or more lacunar infarcts , a single prior infarct > 1 cm3, a single strategically located subcortical infarct (e.g., thalamus, hippocampus, left caudate head), evidence of a meningioma, cerebral contusion, encephalomalacia, or aneurysms, evidence of other dementia (non-AD) pathology. -Operation (under general anaesthesia) within 3 months prior to study entry and scheduled elective operation during the whole study period. -History and/or presence of autoimmune disease. -Recent (≤5 years since last specific treatment) history of cancer (Exceptions: basal cell carcinoma, intraepithelial cervical neoplasia). -Active infectious disease (e.g., Hepatitis B, C). - Presence and/or history of Immunodeficiency (e.g., HIV). -Significant systemic illness (e.g., chronic renal failure, chronic liver disease, poorly controlled diabetes, poorly controlled congestive heart failure, other deficiencies). -Hypothyroidism, defined as any significant thyroid-stimulating hormone elevation. Patients with corrected hypothyroidism are eligible for the study provided that treatment has been stable for 3 months before study entry. -History of significant psychiatric illness such as schizophrenia, bipolar affective disorder or psychotic depression. -Current depressive episode (Geriatric Depression Scale (GDS) >5 at Visit 1) -Metabolic or toxic encephalopathy or dementia due to a general medical condition. -Alcoholism or substance abuse within the past year (alcohol or drug intoxication). -Wernicke’s encephalopathy -History or evidence of any other CNS disorder that could be interpreted as a cause of dementia (infectious or inflammatory/demyelinating CNS conditions, Creutzfeld Jacob disease, Parkinson’s disease, Huntington’s disease, brain tumor, subdural haematoma, etc.) -History or evidence of cerebrovascular disease (stroke, transient ischemic attack, hemorrhage), or diagnosis of possible, probable or definite vascular dementia in accordance with NINDS-AIREN criteria. -Epilepsy. -Prior and/or current treatment with experimental immunotherapeutics including IVIG, AD antibody therapy and/or vaccines for AD including AFFITOPE AD01&AD02. -Prior and/or current treatment with immunosuppressive drugs. -Benzodiazepines administered on a chronic basis. -Change in dose of standard treatments for AD or hypothyroidism within 3 months prior to Visit 1. -Change in dose of previous and current medications which the patient is taking because of consisting illnesses according medical history (except AD and hypothyreoidism therapies, AD therapies will be recorded separately) within the last 30 days prior to Visit 1, if clinically relevant. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of the present clinical trial is to assess the clinical activity of various doses / formulations of AFFITOPE AD02 following its repeated s.c. administration to patients with mild AD, based on the evaluation of the cognitive and functional domains.
This clinical trial will be considered positive if one or all treatment groups do better than the pooled placebo group in the primary endpoints of the study (cognitive and functional disease domain) |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
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 | Information not present in EudraCT |
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 |
|
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
|
from 360 evaluable patients the last visit of last patient |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |