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18-months Safety Follow-up Study of AADvac1, an Active Tau Vaccine for Alzheimer's Disease (FUNDAMANT)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02031198
First Posted: January 9, 2014
Last Update Posted: March 17, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Axon Neuroscience SE
January 7, 2014
January 9, 2014
March 17, 2017
January 2014
August 2016   (Final data collection date for primary outcome measure)
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 ]

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

Same as current
Complete list of historical versions of study NCT02031198 on ClinicalTrials.gov Archive Site
  • Immunogenicity of AADvac1 [ Time Frame: Immune response to the vaccine will be assessed over 18 month ]

    Measurement of:

    Titres of antibodies reactive with AADvac1 Titres of antibodies reactive with Alzheimer tau protein Antibody isotype profiles

  • Patient cognition [ Time Frame: 18+ months ]

    Tests used:

    ADAS-Cog (Alzheimer's Disease Assessment Scale-cognitive subscale) COWAT (Controlled oral word association test) Category fluency

Same as current
Not Provided
Not Provided
 
18-months Safety Follow-up Study of AADvac1, an Active Tau Vaccine for Alzheimer's Disease
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"

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.

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.

Interventional
Phase 1
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Alzheimer's Disease
Drug: AADvac1
Active immunization against pathological Alzheimer's disease tau protein
Other Names:
  • Axon peptide 108 (coupled to KLH), 40ug/0.3mL
  • Axon peptide 108 conjugated to KLH
Experimental: AADvac1

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.

Intervention: Drug: AADvac1
Novak P, Schmidt R, Kontsekova E, Zilka N, Kovacech B, Skrabana R, Vince-Kazmerova Z, Katina S, Fialova L, Prcina M, Parrak V, Dal-Bianco P, Brunner M, Staffen W, Rainer M, Ondrus M, Ropele S, Smisek M, Sivak R, Winblad B, Novak M. Safety and immunogenicity of the tau vaccine AADvac1 in patients with Alzheimer's disease: a randomised, double-blind, placebo-controlled, phase 1 trial. Lancet Neurol. 2017 Feb;16(2):123-134. doi: 10.1016/S1474-4422(16)30331-3. Epub 2016 Dec 10.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
25
December 2016
August 2016   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Completion of visit V8 of the AADvac1 phase I study AXON CO 18700 (EUDRACT 2012-003916-29).
  2. Informed consent capability (as determined by an independent neurologist/psychiatrist).
  3. Written informed consent signed and dated by the patient and the caregiver.
  4. Availability of a partner/caregiver knowing the patient and being able to accompany the patient to the visits
  5. Adequate visual and auditory abilities and language skills to allow neuropsychological testing.
  6. Female patients are only eligible for the study if they are either surgically sterile or at least 2 years postmenopausal.
  7. Sexually active males must be using reliable contraception methods (i.e. condoms) or be surgically sterile.

Exclusion Criteria:

  1. Pregnant women.
  2. Participation in another clinical trial during the course of this study.
  3. Contraindication for MRI imaging such as MRI-incompatible metallic endoprosthesis or MRI-incompatible stent implantation
  4. History and/or presence of autoimmune disease, if considered relevant by the investigator.
  5. Significant systemic illness (e.g., chronic renal failure, chronic liver disease, poorly controlled diabetes, poorly controlled congestive heart failure, congenital long QT syndrome, other deficiencies), if considered relevant by the investigator.
  6. Current treatment with immunosuppressive drugs.
Sexes Eligible for Study: All
50 Years to 86 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Austria
 
 
NCT02031198
AC-AD-002
2013-004499-36 ( EudraCT Number )
Yes
Not Provided
Not Provided
Axon Neuroscience SE
Axon Neuroscience SE
Not Provided
Principal Investigator: Reinhold Schmidt, Professor Medizinische Universität Graz
Axon Neuroscience SE
March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP