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

NCT01850238 | Completed Phase 1 DMC

• 2 other identifiers: AXON CO 187002012-003916-29
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Alzheimer Disease

Keywords

Alzheimer disease; tau protein; neurofibrillary degeneration; disease-modifying

Outcome Measures

Primary Outcomes (1)

• Tolerability and safety profile of AADvac1 in patients with mild-to-moderate Alzheimer's disease

  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

  Tolerability & safety are assessed over a period of 3 months / 3 administrations

Secondary Outcomes (1)

• Immunogenicity of AADvac1

  Immune response to the vaccine will be assessed over 3 months / 3 administrations

Other Outcomes (1)

• Patient cognition

  3 months / 3 administrations, with an optional 3 months open label extension phase (3+3 administrations)

Study Arms (2)

Placebo (adjuvant in saline solution)

PLACEBO COMPARATOR

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.

Other: Placebo

AADvac1

EXPERIMENTAL

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.

Biological: AADvac1

Interventions

AADvac1 BIOLOGICAL

AADvac1 is intended as an active vaccination for disease-modifying treatment of Alzheimer's disease.

Also known as: (no commercial or INN name assigned yet)

AADvac1

Placebo OTHER

The placebo contains the same buffer and adjuvant as AADvac1, but lacks the API.

Also known as: (no other names)

Placebo (adjuvant in saline solution)

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of probable Alzheimer's disease based on the NINCDS/ADRDA criteria.
• MMSE 15-26.
• stable dose of Alzheimer's Disease treatment since 3 months before screening visit or being untreated.
• Hachinski Ischemia Scale ≤ 4.
• MRI consistent with the diagnosis of AD.
• Informed consent capability
• Written informed consent signed and dated by the patient \& caregiver.
• Age between 50 and 85 years.
• Availability of partner/caregiver.
• Adequate visual and auditory abilities and German language skills for neuropsychological testing.
• Females either surgically sterile or 2+ years postmenopausal.
• 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.
• Sexually active males must be using reliable contraception methods or be surgically sterile.

You may not qualify if:

• Pregnant women.
• Participation in another clinical trial within 3 months before Visit 1.
• Patients not expected to complete the clinical trial.
• Presence or history of allergy to components of the vaccine, if considered relevant by the investigator.
• Contraindication for MRI imaging (e.g. metallic endoprosthesis, stent implantation in the last 6 months).
• 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
• Surgery (under general anaesthesia) within 3 months prior to study entry and scheduled surgery during the whole study period.
• History and/or presence of autoimmune disease, if considered relevant by the investigator.
• Recent (≤3 years since last specific treatment) history of cancer (Exceptions: basal cell carcinoma, intraepithelial cervical neoplasia).
• Active infectious disease (e.g., Hepatitis B, C).

Sponsors & Collaborators

• Axon Neuroscience SE: lead

Study Sites (3)

Univeristätsklinik für Neurologie, PMU, Christian-Doppler Klinik

Salzburg, Salzburg, 5020, Austria

Location

Medizinische Universitat Graz

Graz, Styria, 8036, Austria

Location

Medizinische Universitat Wien

Vienna, Vienna, 1090, Austria

Location

Related Publications (3)

• Novak P, Schmidt R, Kontsekova E, Kovacech B, Smolek T, 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, Zilka N, Winblad B, Novak M. FUNDAMANT: an interventional 72-week phase 1 follow-up study of AADvac1, an active immunotherapy against tau protein pathology in Alzheimer's disease. Alzheimers Res Ther. 2018 Oct 24;10(1):108. doi: 10.1186/s13195-018-0436-1.

  PMID: 30355322 DERIVED

• 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.

  PMID: 27955995 DERIVED

• Kontsekova E, Zilka N, Kovacech B, Novak P, Novak M. First-in-man tau vaccine targeting structural determinants essential for pathological tau-tau interaction reduces tau oligomerisation and neurofibrillary degeneration in an Alzheimer's disease model. Alzheimers Res Ther. 2014 Aug 1;6(4):44. doi: 10.1186/alzrt278. eCollection 2014.

  PMID: 25478017 DERIVED

MeSH Terms

Conditions

Alzheimer Disease; Frontotemporal Dementia

Interventions

AADvac1

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Frontotemporal Lobar Degeneration; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Reinhold Schmidt, Professor

  Medizinische Universität Graz

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2013
• First Posted: May 9, 2013
• Study Start: May 1, 2013
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: October 12, 2015

Record last verified: 2015-10

Locations

AU (3)