Alzheimer's disease MedDRA version: 20.0 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852
Conditions
Sponsors
Araclon Biotech, S.L.
Eligibility
Sex/Gender
All
Inclusion criteria
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. 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 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 90
Exclusion criteria
Exclusion criteria: 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, as defined by plasma creatinine =2.5 mg/dL (221 µmol/l) and/or total bilirubin >3 mg/dL (51.3 µmol/l) measured at the local site laboratory. 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 documenta
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Safety Objective: - To evaluate the safety and tolerability of repeated doses of ABvac40 in a population of patients with a-MCI or vm-AD. Primary Efficacy (Immunogenicity) Objective: - To assess the immune response produced during the study by repeated doses of ABvac40 in a population of a-MCI or vm-AD.;Secondary Objective: Secondary (Exploratory) Efficacy Objectives: - To characterize the immune response elicited by repeated doses of ABvac40 in a population of a-MCI or vm-AD. - To assess the changes in the disease biomarkers elicited by ABvac40 in the overall study population - To assess the changes in cognition and quality of life elicited by ABvac40 in the overall study population Exploratory Safety Objective -To evaluate the safety and tolerability of repeated doses of ABvac40 after delayed start in patients receiving placebo during Part A, and the long-term safety and tolerability of ABvac40 in patients receiving a booster after their Part A vaccination scheme Exploratory Efficacy Objectives Immunogenicity -To assess the immune response produced by repeated doses of ABvac40 after delayed start in patients receiving placebo during Part A. -To assess the immune response triggered by a second ABvac40 booster in patients receiving ABvac40 during Part A ;Primary end point(s): The primary safety endpoint: the incidence of AEs (overall or grouped as neurological, psychiatric or cardiovascular). Primary efficacy endpoint: the average maximal increment (M?) of anti-Aß40 antibody signal (OD in ELISA) ) in each subject with regard to the pre-treatment visit (either V0 or V1).;Timepoint(s) of evaluation of this end point: Primary Safety Endpoint: All visits Primary Efficacy Endpoint: V0, V1, V3, V6, V9, V12, V15, V16, V17, V20, V21, V23 and V25. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary safety endpoints: - number of withdrawn patients due to adverse events (AEs) - number of withdrawn patients due to other causes - number of serious adverse events (SAEs) - number of clinically significant changes in physical and neurological examination -number and type of concomitant medications - number of clinically significant changes in vital signs (blood pressure, heart rate, respiratory rate, body temperature), body mass (weight, height). - number of clinically significant changes in brain MRI - number of clinically significant changes in electrocardiogram (EKG) - number of clinically significant changes in analytical haematology, biochemistry, coagulation, serology and urine test strip results. Secondary Efficacy endpoints: Additionally, the following secondary efficacy endpoints will be evaluated including: - Characterization of the immune response: o Levels of anti-KLH and anti-Aß42 antibodies in plasma. o Level of anti-Aß40 antibodies in CSF o Levels of cytokines in plasma including IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-15, TNF-a and IFN-?. o Analysis of the peripheral blood cell subsets by immunophenotyping o Levels of antibody secreting cells and cytokine-secreting cells (including IFN-?, TNF-a and IL-13) - Assessment of disease biomarkers: o Levels of Aß peptides in plasma o Cortical fibrillary amyloid deposition assessed by PET scans. o Levels of CSF biomarkers (Aß42, Tau, P-tau, neurofilament light and neurogranin) and other Aß peptide species o Brain volumetric and atrophy of the hippocampus using magnetic resonance imaging - Assessment of cognition and quality of life: o Mini Mental State Examination (MMSE) o Clinical Dementia Rating scale (CDR) o Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Alzheimer’s Disease Cooperative Study – Activities of Daily Living, Mild Cognitive Impairment (ADCS-ADL MCI) o COLUMBIA Suicide Severity Rating Scale (C-SSRS) o Trail Making Test (TMT) o Euroqo | — |
Countries
France, Italy, Spain, Sweden
Contacts
Public ContactBelén García Alonso
Araclon Bitech S.L.
Outcome results
None listed