Alzheimer's disease MedDRA version: 19.1 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. 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. Presence of up to 3 microhemorrhages will be acceptable. 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. The vaccination against influenza, must be avoided within 3 months before inclusion. 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 r
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 (quantify) 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 study population stratified by amyloid-PET positivity. - To assess the changes in cognition and quality of life elicited by ABvac40 in the study population stratified by amyloid-PET positivity.;Primary end point(s): The primary endpoint for safety is the incidence of AEs (overall or grouped as neurological, psychiatric or cardiovascular). The hypothesis for the primary endpoint for safety is that ABvac40 will be safe for human administration, according to the observed pattern of AEs. The trial will be considered satisfactory if the pattern of AEs (overall or grouped as neurological, psychiatric or cardiovascular) is consistent with a good safety and tolerability profile of ABvac40 for human administration at the final visit. The primary efficacy endpoint is the average maximal increment (M?) of anti-Aß40 antibody signal (OD in ELISA). The hypothesis for the primary efficacy endpoint for is that ABvac40 will elicit immune responses to Aß40 (statistical superiority compared to placebo). The trial will be considered successfully confirmatory regarding efficacy (immunogenicity) of ABvac40 if the average maximal increment (M?) of anti-Aß40 antibody signal (OD in ELISA) in the verum group is = 1.778 OD than the average M? in the placebo group (the difference reached between both groups in the phase I clinical trial of ABvac40) at the final of the study.;Timepoint(s) of evaluation of th | — |
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 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 urinalysis Secondary efficacy endpoints: - Characterization of the immune response: · Levels of Aß peptides in plasma. · Level of anti-Aß40 antibodies in CSF · Levels of cytokines in plasma including IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-15, TNF-a and IFN-?. · Relative number of peripheral blood mononuclear cells (cluster of differentiations; CD) including CD3, CD4, CD8, CD19, CD25, CD27 and CD69. · Levels of antibody secreting cells and cytokine-secreting cells (including IFN-?, TNF-a and IL-13) - Assessment of disease biomarkers: · Levels of Aß peptides in plasma · Cortical fibrillary amyloid deposition assessed by PET scans. · Levels of CSF biomarkers (Aß42, Tau, P-tau and neurogranin) and other Aß peptide species · Brain volumetric and atrophy of the hippocampus using magnetic resonance imaging - Assessment of cognition and quality of life: · Mini Mental State Examination (MMSE) · Clinical Dementia Rating scale (CDR) · Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) · Alzheimer’s Disease Cooperative Study – Activities of Daily Living, Mild Cognitive Impairment (ADCS-ADL MCI) · COLUMBIA Suicide Severity Rating Scale (C-SSRS) · Trail Making Test (TMT) · Euroqol 5 Dimensions (EQ-5D);Timepoint(s) of evaluation of this end point: Secondary sa | — |
Countries
France, Italy, Spain, Sweden
Contacts
Public ContactItziar San José
Araclon Bitech S.L.
Outcome results
None listed