18-months Safety Follow-up Study of AADvac1, an Active Tau Vaccine for Alzheimer's Disease (FUNDAMANT)
This follow-up study continues to observe patients who have completed the phase 1 trial of AADvac1, for another 18 months.
Long-term safety and behavior of the immune response to AADvac1 over time are the main points of interest.
AADvac1 is a vaccine directed against pathologically modified Alzheimer tau protein that is the main constituent of neurofibrillary tangles (NFTs), and is intended to be a disease-modifying treatment for Alzheimer's disease, i.e. to halt its progress.
As this study is a Phase I study focused on tolerability and safety, efficacy will be assessed in an exploratory manner.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An 18-months Open Label Phase I Follow-up Study on Patients With Alzheimer's Disease Who Have Completed the AADvac1 Phase I Study "AXON CO 18700"|
- Tolerability and safety profile of AADvac1 in patients with mild-to-moderate Alzheimer's disease [ Time Frame: Tolerability & safety are assessed over a period of 18+ months ] [ Designated as safety issue: Yes ]
Safety is assessed via recording of all Adverse Events and Adverse Events
Patients are observed via:
MRI Clinical & neuro-psychiatric observation Cognitive testing ECG Blood biochemistry, hematology, coagulation measurement Urine analysis
- Immunogenicity of AADvac1 [ Time Frame: Immune response to the vaccine will be assessed over 18 month ] [ Designated as safety issue: No ]
Titres of antibodies reactive with AADvac1 Titres of antibodies reactive with Alzheimer tau protein Antibody isotype profiles
- Patient cognition [ Time Frame: 18+ months ] [ Designated as safety issue: Yes ]
ADAS-Cog (Alzheimer's Disease Assessment Scale-cognitive subscale) COWAT (Controlled oral word association test) Category fluency
|Study Start Date:||January 2014|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||August 2016 (Final data collection date for primary outcome measure)|
Patients who have received 6 doses in the previous trial will be administered 1-2 booster doses of AADvac1 (2 if their antibody titers decline below those achieved in the previous trial).
Patients who have received 3 doses in the previous trial will be administered another 3 doses, then vaccinated with booster doses as above.
Active immunization against pathological Alzheimer's disease tau protein
AADvac1 is a candidate therapeutic vaccine for Alzheimer's disease that targets misfolded tau protein, a common denominator of neurofibrillary pathology. Based on preclinical results, the intervention is expected to reduce the number of neurofibrillary tangles, remove hyperphosphorylated tau protein and reduce the amount of oligomerized and insoluble pathological tau in the brain, to halt the spread of neurofibrillary pathology through the brain, and thus prevent associated cognitive decline.
The vaccine's antigenic determinant is a synthetic peptide derived from a tau protein sequence, which is coupled to keyhole limpet hemocyanin (KLH) and uses aluminum hydroxide (Alhydrogel) as an adjuvant.
At present AADvac1 is intended as an active immunotherapy for patients with diagnosed Alzheimer's disease (AD). According to need, patients will receive additional immunization doses beyond those administered in the preceding pase 1 trial; the raised titers of therapeutic antibodies and possible benefits of the treatment can extend beyond the duration of the study.
Because of the central role of pathological misfolded tau protein in the etiology of AD, the vaccine is expected to be more effective than active or passive immunotherapies aiming to eliminate the amyloid β plaques that have been clinically investigated so far.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02031198
|Medizinische Universitat Graz|
|Graz, Steiermark, Austria, 8036|
|Univeristätsklinik für Neurologie, PMU, Christian-Doppler Klinik|
|Salzburg, Austria, 5020|
|Medizinische Universitat Wien|
|Wien, Austria, 1090|
|Sozialmedizinisches Zentrum Ost (SMZ Ost) /Donauspital, Memory Clinic and Karl Landsteiner Institut for Amnestic disorders|
|Wien, Austria, A-1220|
|Principal Investigator:||Reinhold Schmidt, Professor||Medizinische Universität Graz|