Safety and Immunogenicity of Repeated Doses of ABvac40 in Patients With a-MCI or Vm-AD

This is an interventional treatment trial for Mild Cognitive Impairment Read More

Inclusion Criteria:

A subject must meet all the following inclusion criteria:

1. Male or female between 55 and 80 years of age, both inclusive, at the time of signing informed consent.
2. The patient (or legal representative, if applicable) and a close relative/caregiver must read the subject information sheet, agree to participate in the clinical trial and sign the informed consent form (the patient and a close relative/caregiver).
3. Presence of a stable caregiver to attend the patient study visits.
4. Mini-Mental Status Examination (MMSE) score between 24 and 30 points (inclusive), according to age and education level.
5. Clinical Dementia Rating (CDR) scale scoring 0.5.
6. Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score on the Delayed Memory Index (DMI) of 85 or lower.
7. The results of the patient's MRI brain scan must be concordant with the diagnosis of clinical a-MCI or vm-AD according to the following criteria: Scheltens scale, and measurement of white matter and past haemorrhages.
8. If the patient is receiving treatment for AD, must have been stable during the two months before the selection visit.
9. Treatment for concomitant diseases must be stable during the previous month before the treatment of the study.
10. Positive assessment of the candidate by the investigator for complying with the requirements and procedures of the study.

Exclusion Criteria:

A subject meeting any of the following exclusion criteria is NOT eligible for participation in the study.

1. Known allergy to components of the vaccine or prior history of anaphylaxis, a severe allergic reaction or a history of hypersensitivity to any component of the formulation. Allergy to fish or shellfish.
2. Active infectious disease (i.e. hepatitis B, C). Positive syphilis serology.
3. History or presence of autoimmune disease, except mild eczema, rhinitis or psoriasis.
4. Presence or history of immunodeficiency (i.e. HIV).
5. Significant kidney and/or liver disease.
6. History of asthma or reactive airway disease with bronchospasm in the last 6 months, or currently on regular treatment.
7. Major uncontrolled systemic condition (e.g. diabetes, congestive heart failure, hypertension).
8. History of cancer (≤5 years since the last specific treatment). Exceptions: basocellular carcinoma.
9. Significant alterations in hematological, biochemical or urine analytical parameters, particularly those relating to levels of vitamin B12, folic acid or thyroid tests.
10. History of any other central nervous system disorder, degenerative or non-degenerative neurological or psychiatric condition that, in the investigator's opinion could be the cause of the dementia, or could explain the cognitive impairment, or that might interfere with cognitive function directly or by its treatment.
11. Geriatric Depression Scale (GDS; abbreviated version), score >5
12. Has a "yes" answer to C-SSRS suicidal ideation items 4 or 5, or any suicidal behavior within 6 months before Screening, or has been hospitalized or treated for suicidal behavior in the past 5 years before Screening.
13. History or signs of cerebrovascular disease (ischemic or haemorrhagic stroke, transient ischemic attack), or diagnosis of possible, probable or clear vascular dementia according to NINDS-AIREN criteria.
14. Presence on MRI of a relevant pattern of microvascular disease (Leukoaraiosis, Fazekas score ≥2 in the deep white matter scale or ≥4 in the global score) or more than one lacunar or territorial infarcts. Any other MRI finding that, in the opinion of the investigator, might be a relevant contributing cause of subject´s cognitive impairment. Presence of up to 3 microhemorrhages will be acceptable.
15. History of bleeding disorder or predisposing conditions, blood clotting or clinically significant abnormal results on coagulation profile at Screening, as determined by the Investigator.
16. Patients being treated with anticoagulants or antiaggregant therapy (aspirin at a prophylactic dose ≤ 325 mg daily or clopidogrel at a dose ≤75 mg daily are allowed) should not be recruited in the study.
17. Modified Hachinski Ischemic Scale, score higher than 4.
18. Surgery (with general anaesthetic) within the previous three months to be included in the trial, or programed during the study period.
19. Treatment within 30 days prior to visit 0 with systemic corticosteroids or other immunosuppressant's.
20. Vaccination against influenza or any other vaccination within 2 months before first IMP dose.
21. Patients, who have previously been randomized in this trial.
22. Participation in another clinical trial within the previous 1 month to screening visit, or within the previous 12 months after the last dose to the screening visit in the case of subjects who participated in trials with a study drug whose intention was to modify the progression AD unless documentation of receipt of placebo is available. The patient cannot be included in the study if the experimental drug was an immunotherapeutic drug, including IVIG or a vaccine against Alzheimer's disease unless documentation of receipt of placebo is available.
23. Patients with alcohol or drug abuse or dependence.
24. Absolute (having a pacemaker or implantable defibrillator) or relative (bare metal stent or stent implanted in the last six months) contraindications to MRI examination. Feeling of claustrophobic do not let perform MRI or PET scan.
25. Patients unlikely to comply with the protocol (e.g., unable to return for follow-up visits).
26. Women of childbearing potential, pregnant or nursing.
27. Significant alterations in the EKG that are associated with an added risk for the patient.