Safety Study of AADvac1, a Tau Peptide-KLH-Conjugate Active Vaccine to Treat Alzheimer's Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by Axon Neuroscience SE
Sponsor:
Information provided by (Responsible Party):
Axon Neuroscience SE
ClinicalTrials.gov Identifier:
NCT01850238
First received: May 7, 2013
Last updated: November 10, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Alzheimer Disease
Drug: AADvac1
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Axon Neuroscience SE:

Primary Outcome Measures:
  • 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:

    • MRI
    • Clinical & neuro-psychiatric observation
    • Cognitive testing
    • ECG
    • Blood biochemistry, hematology, coagulation measurement
    • Urine analysis


Secondary Outcome Measures:
  • Immunogenicity of AADvac1 [ Time Frame: Immune response to the vaccine will be assessed over 3 months / 3 administrations ] [ Designated as safety issue: No ]

    Measurement of:

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


Other Outcome Measures:
  • 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 ]

    Tests used:

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


Estimated Enrollment: 30
Study Start Date: May 2013
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Experimental: AADvac1

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.

Drug: AADvac1
AADvac1 is intended as an active vaccination for disease-modifying treatment of Alzheimer's disease.
Other Name: (no commercial or INN name assigned yet)

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   50 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis of probable Alzheimer's disease based on the NINCDS/ADRDA criteria.
  2. MMSE 15-26.
  3. stable dose of Alzheimer's Disease treatment since 3 months before screening visit or being untreated.
  4. Hachinski Ischemia Scale ≤ 4.
  5. MRI consistent with the diagnosis of AD.
  6. Informed consent capability
  7. Written informed consent signed and dated by the patient & caregiver.
  8. Age between 50 and 85 years.
  9. Availability of partner/caregiver.
  10. Adequate visual and auditory abilities and German language skills for neuropsychological testing.
  11. Females either surgically sterile or 2+ years postmenopausal.
  12. Participant on stable doses of all medications for concomitant illnesses according to medical history for at least 30 days prior to Visit 1 if considered relevant by the investigator.
  13. Sexually active males must be using reliable contraception methods or be surgically sterile.

Exclusion Criteria:

  1. Pregnant women.
  2. Participation in another clinical trial within 3 months before Visit 1.
  3. Patients not expected to complete the clinical trial.
  4. Presence or history of allergy to components of the vaccine, if considered relevant by the investigator.
  5. Contraindication for MRI imaging (e.g. metallic endoprosthesis, stent implantation in the last 6 months).
  6. Any of the following detected by brain MRI:

    • Thromboembolic infarction
    • Other focal lesions which may be responsible for the cognitive status of the patient
    • More than one lacunar infarct with a diameter of less than 1.5 cm in any dimension
    • Any lacunar infarct in a strategically important location such as the thalamus, hippocampus of either hemisphere, head of the left caudate
    • White matter lesions involving more than 25% of the hemispheric white matter
  7. Surgery (under general anaesthesia) within 3 months prior to study entry and scheduled surgery during the whole study period.
  8. History and/or presence of autoimmune disease, if considered relevant by the investigator.
  9. Recent (≤3 years since last specific treatment) history of cancer (Exceptions: basal cell carcinoma, intraepithelial cervical neoplasia).
  10. Active infectious disease (e.g., Hepatitis B, C).
  11. Presence and/or history of Immunodeficiency (e.g., HIV).
  12. Significant systemic illness, if considered relevant by the investigator.
  13. Hypothyroidism (patients with corrected hypothyroidism are eligible for the study if treatment has been stable for 3 months before study entry)
  14. History of significant psychiatric illness such as schizophrenia, bipolar affective disorder or major depression.
  15. Current depressive episode (Geriatric Depression Scale GDS >5 at Visit 1).
  16. Metabolic or toxic encephalopathy or dementia due to a general medical condition.
  17. Alcoholism or substance abuse within the past year (alcohol or drug intoxication).
  18. Wernicke's encephalopathy
  19. History or evidence of any other CNS disorder that could be the cause of dementia (infectious or inflammatory/demyelinating CNS conditions, Creutzfeldt-Jakob disease, Parkinson's disease, Huntington's disease, brain tumour, subdural haematoma, etc.)
  20. History or evidence of cerebrovascular disease (ischemic or haemorrhagic stroke, transient ischemic attack), or diagnosis of possible, probable or definite vascular dementia.
  21. Epilepsy.
  22. Prior and/or current treatment with experimental immunotherapeutics including IVIG or any vaccines for AD.
  23. Current treatment with immunosuppressive drugs.
  24. Change in dose of standard treatments for AD or hypothyroidism within 3 months prior to visit 1.
  25. Change in dose of previous and current medications which the patient is taking because of consisting illnesses according medical history within the last 30 days prior to visit 1, if considered clinically relevant by the investigator.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01850238

Contacts
Contact: Reinhold Schmidt, Professor +43-316-385-83397 reinhold.schmidt@medunigraz.at

Locations
Austria
Medizinische Universitat Graz Recruiting
Graz, Steiermark, Austria, 8036
Contact: Reinhold Schmidt, Professor    +43-316-385-83397    reinhold.schmidt@medunigraz.at   
Principal Investigator: Reinhold Schmidt, Professor         
Univeristätsklinik für Neurologie, PMU, Christian-Doppler Klinik Recruiting
Salzburg, Austria, 5020
Contact: Wolfgang Staffen, Professor       w.staffen@salk.at   
Contact: Daniela Sinadinoska    +43-662-4483-3120    CDK-Studien@salk.at   
Principal Investigator: Wolfgang Staffen, Professor         
Medizinische Universitat Wien Recruiting
Wien, Austria, 1090
Contact: Peter Dal-Bianco, Professor    +43 1 3203334    peter.dal-bianco@meduniwien.ac.at   
Principal Investigator: Peter Dal-Bianco, Professor         
Sponsors and Collaborators
Axon Neuroscience SE
Investigators
Principal Investigator: Reinhold Schmidt, Professor Medizinische Universität Graz
  More Information

No publications provided

Responsible Party: Axon Neuroscience SE
ClinicalTrials.gov Identifier: NCT01850238     History of Changes
Other Study ID Numbers: AXON CO 18700, 2012-003916-29
Study First Received: May 7, 2013
Last Updated: November 10, 2013
Health Authority: Austria: Agency for Health and Food Safety

Keywords provided by Axon Neuroscience SE:
Alzheimer disease
tau protein
neurofibrillary degeneration
disease-modifying

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on August 18, 2014