Safety Study of AADvac1, a Tau Peptide-KLH-Conjugate Active Vaccine to Treat Alzheimer's Disease
This first-time-in-man study is mainly designed to assess the safety and tolerability of AADvac1 in the treatment of Alzheimer's disease.
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:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A 3-months Randomized, Placebo-controlled, Parallel Group, Double-blinded, Multi-centre, Phase I Study to Assess Tolerability & Safety of AADvac1 Applied to Patients With Mild-Moderate Alzheimer's Disease With 3-months Open Label Extension|
- 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 3 months / 3 administrations ] [ Designated as safety issue: Yes ]
Safety is assessed via recording of all Adverse Events and Adverse Events
Patients are observed via:
- Clinical & neuro-psychiatric observation
- Cognitive testing
- Blood biochemistry, hematology, coagulation measurement
- Urine analysis
- Immunogenicity of AADvac1 [ Time Frame: Immune response to the vaccine will be assessed over 3 months / 3 administrations ] [ 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: 3 months / 3 administrations, with an optional 3 months open label extension phase (3+3 administrations) ] [ 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:||May 2013|
|Study Completion Date:||March 2015|
|Primary Completion Date:||March 2015 (Final data collection date for primary outcome measure)|
Placebo Comparator: Placebo (adjuvant in saline solution)
Placebo patients will receive 1 dose of placebo per month over 3 months, for a total of 3 administrations.
Placebo consists of vaccine adjuvant in saline solution. Placebo is administered subcutaneously.
The placebo contains the same buffer and adjuvant as AADvac1, but lacks the API.
Other Name: (no other names)
AADvac1 patients will receive 1 dose of AADvac1 per month over 3 months, for a total of 3 administrations.
AADvac1 is a vaccine (single-use vials with solution ready for injection) AADvac1 is administered subcutaneously.
AADvac1 is intended as an active vaccination for disease-modifying treatment of Alzheimer's disease.
Other Name: (no commercial or INN name assigned yet)
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). Patients will receive 3 - 6 immunization doses; 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: NCT01850238
|Medizinische Universitat Graz|
|Graz, Steiermark, Austria, 8036|
|Univeristätsklinik für Neurologie, PMU, Christian-Doppler Klinik|
|Salzburg, Austria, 5020|
|Medizinische Universitat Wien|
|Wien, Austria, 1090|
|Principal Investigator:||Reinhold Schmidt, Professor||Medizinische Universität Graz|