Clinical trial NCT02579252 (phase 2, status: completed)
Conditions: alzheimer's disease
ICD codes: G30.8, G30.9, G30.0, G30.1
Drugs: placebo
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion criteria (abbreviated):

          -  Diagnosis of probable Alzheimer's disease according to the revised National Institute
             on Aging-Alzheimer's Association (NIA-AA) criteria (McKhann 2011).

          -  Mini Mental State Examination (MMSE) score ≥ 20 and ≤ 26.

          -  Brain MRI finding consistent with the diagnosis of Alzheimer's disease

          -  Medial temporal lobe atrophy: Scheltens score of ≥ 2 (on a scale of 0-4 on the more
             atrophied side) AND/OR positive AD biomarker profile in the CSF (amyloid+, tau+)

          -  At least 6 years of formal elementary education.

          -  Age 50-85 years.

          -  Fluency in the local language and sufficient auditory and visual capacities to allow
             neuropsychological testing.

          -  Ability to read and understand the informed consent.

          -  Stable therapy with an acetylcholinesterase inhibitor for at least 3 months prior to
             screening.

          -  If the patient is on memantine treatment, the dose regimen must be stable for at least
             3 months prior to screening.

          -  Hachinski Ischemia Scale score ≤ 4.

          -  Availability of a caregiver.

          -  Female patients must be either surgically sterile or at least 2 years postmenopausal.

          -  Male patients must either be surgically sterile, or he and his female spouse/partner
             who is of childbearing potential must be using highly effective contraception starting
             at screening and continuing throughout the study period.

          -  Patient provides written informed consent.

        Exclusion criteria (abbreviated):

          -  Participation in another clinical study within 3 months prior to screening.

          -  Pregnant or breastfeeding female.

          -  Not expected to complete the clinical study.

          -  Known allergy to components of the vaccine.

          -  Contraindication for MRI imaging.

          -  Any of the following detected by brain MRI:

               -  Infarction in the territory of large vessels

               -  More than one lacunar infarct.

               -  Any lacunar infarct in a strategically important location.

               -  Confluent hemispheric deep white matter lesions (Fazekas grade 3).

               -  Other focal lesions which may be responsible for the cognitive status of the
                  patient or any other abnormalities associated with significant central nervous
                  disease other than Alzheimer's disease.

          -  Surgery (under general anaesthesia) within 3 months prior to screening and/or
             scheduled surgery (under general anaesthesia) during the whole study period.

          -  Patient has a history and/or currently suffers from a clinically significant
             autoimmune disease, or is expected to receive immunosuppressive or immunomodulatory
             treatment at the present or in the future.

          -  Recent history of cancer (last specific treatment ≤ 5 years prior to Screening).

          -  Myocardial infarction within 2 years prior to screening.

          -  Hepatitis B, C, HIV or Syphilis.

          -  Active infectious disease.

          -  Presence and/or history of immunodeficiency.

          -  Patient currently suffering from a clinically important systemic illness:

               -  poorly controlled congestive heart failure (NYHA ≥ 3)

               -  BMI > 40

               -  poorly controlled diabetes (HbA1c > 7.5%)

               -  severe renal insufficiency (eGFR < 30 mL/min)

               -  chronic liver disease - ALT (alanine aminotransferase) > 66 U/L in females or >
                  80 U/L in males, AST (aspartate aminotransferase) > 82 U/L

               -  QTc interval prolongation in ECG (> 450 ms)

               -  other clinically significant systemic illness, if considered relevant by the
                  investigator

          -  Hypothyroidism, defined as TSH (thyroid-stimulating hormone) elevation > 5.000
             mcIU/mL, and/or FT4 levels < 0.7 ng/dL. Patients with corrected hypothyroidism are
             eligible for the study provided that treatment has been stable for 3 months before
             study entry.

          -  Valid diagnosis of a significant psychiatric illness such as schizophrenia, any type
             of psychotic disorder or bipolar affective disorder.

          -  Current depressive episode (Geriatric Depression Scale GDS ≥ 6) or major depressive
             episode within the last 1 years.

          -  Metabolic or toxic encephalopathy or dementia due to a general medical condition.

          -  History of alcohol or drug abuse or dependence within the past 2 years.

          -  Wernicke's encephalopathy.

          -  History or evidence of any CNS disorder other than AD that could be the cause of
             dementia.

          -  Cerebrovascular disease (ischemic or haemorrhagic stroke), or diagnosis of possible,
             probable or definite vascular dementia.

          -  Epilepsy.

          -  Treatment with experimental immunotherapeutics including intravenous immunoglobulin
             within 3 months prior to screening.

          -  Treatment with experimental therapies for AD aiming at disease-modification within 3
             months prior to screening.

          -  Patient is currently being treated or was treated in the past with any active vaccines
             for AD.

          -  Treatment with immunosuppressive drugs.

          -  Change in dose of previous and current medications within the last 30 days prior to
             Screening (V01), if considered clinically relevant by the investigator.

          -  Vitamin B12 deficiency (serum vitamin B12 < 191 pg/mL).