Clinical trial NCT03113812 (phase 1, status: completed)
Conditions: alzheimer's disease
ICD codes: G30.8, G30.9, G30.0, G30.1
Drugs: abvac40, 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:

          1. Clinical diagnosis suggesting Alzheimer's disease (AD) based on the criteria of the
             National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's
             Disease and Related Disorders Association (NINCDS-ADRDA).

          2. The results of the patient's MRI brain scan had to be concordant with the diagnosis of
             AD according to the following criteria: Scheltens scale, and quantitative measurement
             of white matter and past hemorrhages.

          3. Severity of Alzheimer's disease (AD) assessed as mild or moderate using the Mini
             Mental State Examination (MMSE) scale. Mild or moderate AD was confirmed if the MMSE
             score varied between 15 and 26.

          4. The Hachinski ischemic scale was used to distinguish AD from multi-infarct dementia. A
             score of ≤4 suggested AD.

          5. Score on the Clinical Dementia Rating Scale (CDR) of 0.5 or 1.0.

          6. Be receiving a stable dose of treatment for AD for three months before the selection
             visit, and expecting to continue treatment for the duration of the study (if
             appropriate).

          7. Stable treatment for other illnesses may be administered 30 days prior to V0
             (selection).

          8. Males or females from 50 to 85 years of age, inclusive (at the time of signing
             informed consent).

          9. The patient (or a close relative or legal representative) should read the patient
             information sheet, agreed to participate in the clinical trial and signed Inform
             consent (IC) (the patient and a close relative or legal representative).

         10. Presence of a stable caregiver willing to attend patient visits during the study.

         11. Sufficient visual and auditory capacity to undertake the neuropsychological tests.

         12. Positive assessment of the candidate by the investigator for complying with the
             requirements and procedures of the study.

        Exclusion Criteria:

          1. Pregnant women or women of child-bearing age.

          2. Patients whose general state of health was such that it did not allow completion of
             the trial or that made taking part in the trial difficult, as judged by the
             investigator.

          3. Participation in another clinical trial in the 3 months prior to visit 0 or during the
             12 months prior to the selection visit in the case of patients who had participated in
             trials where the study drug was aimed at modifying the progression of AD.

          4. Known allergy to the vaccine components or history of anaphylaxis, severe allergic
             reaction or history of hypersensitivity to any of the components of the formulation.

             Allergy to fish or shellfish.

          5. Absolute (having a pacemaker or implantable defibrillator) or relative (bare metal
             stent or stent implanted in the last 6 months) contraindications to MRI examination.

          6. Surgery (with general anesthetic) during the 3 months prior to admission into the
             study and/or surgery planned at any point during the study period.

          7. History or presence of autoimmune disease.

          8. Presence or history of immunodeficiency (e.g. HIV).

          9. Recent history of cancer (≤3 years since the last specific treatment). (Exceptions:

             basal-cell carcinoma, intraepithelial cervical neoplasia).

         10. Active infectious disease (e.g. hepatitis B, C) or history of chronic viral hepatitis
             or other chronic hepatic disorders.

         11. Major systemic condition (e.g. chronic renal failure, chronic hepatopathy,
             uncontrolled diabetes, uncontrolled congestive heart failure, other deficiencies).

         12. History of asthma or reactive airway disease presenting as bronchospasm in the last 6
             months or currently on a regular anti-asthmatic drug treatment.

         13. Poorly controlled diseases like poorly controlled hypertension (systolic arterial
             tension >160 mmHg or diastolic arterial tension >100 mmHg, as an average of 3
             measurements) or poorly controlled diabetes according to the investigator's opinion
             (HbA1c > 12.0).

         14. Significant alterations in hematological, biochemical or urine analytical parameters,
             particularly those relating to levels of vitamin B12, folic acid or thyroid tests, and
             including the possibility of clinically significant anemia.

         15. Hypothyroidism, defined as any major alteration in thyrotropin (TSH). Patients with
             corrected hypothyroidism could participate in the study providing that treatment had
             remained stable for three months immediately prior to admission to the study, and
             provided that it was ruled out as the cause of or as contributing to the severity of
             the subject's dementia.

         16. Positive serology for syphilis (except where neurosyphilis had previously been ruled
             out).

         17. History of major psychiatric illness such as schizophrenia, bipolar disorder or major
             depressive disorder during the last year [according to Diagnostic and Statistical
             Manual of Mental Disorders (DSM) -IV criteria)].

         18. Metabolic or toxic encephalopathy or dementia due to a general medical illness.

         19. Abuse or excessive consumption of alcohol or drugs according to the DSM-IV criteria.

         20. Wernicke's encephalopathy.

         21. History or indications of any other Central Nervous System (CNS) disorder that could
             be the cause of the dementia (demyelinating, or infectious or inflammatory CNS
             disease, Creutzfeldt- Jakob disease, Parkinson's disease, Huntington's disease, brain
             tumor, subdural hematoma, etc.).

         22. History or indications of cerebrovascular disease (ischemic or hemorrhagic ictus,
             transient ischemic attack), or diagnosis of possible, probable or definite vascular
             dementia according to NINDS- Association Internationale pour la Recherché et
             l'Enseignement en Neurosciences (AIREN) criteria.

         23. History of intracerebral hemorrhage caused by any of the following: cerebral amyloid
             angiopathy, uncontrolled hypertension, cerebral arteriovenous malformation,
             coagulopathy, CNS vasculitis or any other pathology considered by the investigator
             and/or medical monitor to be a risk factor for intracerebral hemorrhage.

         24. Prior or current treatment with experimental immunotherapies, including Intravenous
             Immunoglobulin (IVIG) or vaccines against AD.

         25. Treatment with systemic corticosteroids or other immunosuppressants during the 30 days
             prior to visit 0.

         26. Change in treatments doses for AD or hypothyroidism during the 3 months prior to visit
             0.

         27. Change in dose of drugs for concurrent illnesses appearing in the patient's clinical
             history during the 30 days prior to visit 1, if they were clinically relevant.

         28. Patients who had been previously included in the trial, except those patients who
             failed the screening for reasons that had since been resolved, and so their re-entry
             into the trial could be considered. Those who received their randomization number and
             then left the trial remained excluded.