24 Months Safety and Efficacy Study of AADvac1 in Patients With Mild Alzheimer's Disease

NCT02579252 | Completed Phase 2 DMC

• 2 other identifiers: AC-AD-0032015-000630-30
• Study Type: interventional
• Target: 208
• Locations: 7 countries
• Sites: 33

Brief Summary

This study evaluates the safety and efficacy of AADvac1 in the treatment of patients with mild Alzheimer's disease. 60% of participants will receive AADvac1 and 40% of participants will receive placebo.

Conditions

Alzheimer's Disease

Keywords

vaccine; tau protein; active; immunization; KLH; immunotherapy; tau

Outcome Measures

Primary Outcomes (1)

• Safety (all-case treatment-emergent adverse events except local reactions)

  The safety and tolerability of AADvac1 in the treatment of patients with mild Alzheimer disease, as assessed by AEs, vital signs, ECG, laboratory measures, MRI of the brain, physical and neurological examination, Columbia Suicide Severity Rating Scale (C-SSRS) and review of the Patient Diary

  24 months

Secondary Outcomes (4)

• Clinical Dementia Rating (CDR) Sum of Boxes

  24 months

• Custom cognitive battery (composite standard score)

  24 months

• Alzheimer's Disease Cooperative Study - Activities of Daily Living questionnaire (version for Mild Cognitive Impairment) (ADCS MCI ADL)

  24 months

• Immunogenicity

  24 months

Other Outcomes (3)

• Exploratory: Fludeoxyglucose Positron Emission Tomography (FDG PET) assessment of brain metabolism (change in cerebral glucose metabolic rate expressed as Standardised Uptake Value Ratio [SUVR] change, multiple regions of interest)

  24 months

• Exploratory: MRI volumetry

  24 months

• Exploratory: Cerebrospinal fluid (CSF) biomarkers

  24 months

Study Arms (2)

AADvac1

EXPERIMENTAL

AADvac1 is a suspension for subcutaneous injection. AADvac1 is provided in single-use vials. Dosage: 40 µg Axon peptide 108 (coupled to keyhole limpet haemocyanin (KLH)) using aluminium hydroxide (containing 0.5 mg Al3+) as adjuvant, in a phosphate buffer. Patients receive 6 doses in 4-week intervals, and then 5 individual booster doses in 3-month intervals, for a total of 11 doses.

Biological: AADvac1

Placebo

PLACEBO COMPARATOR

Placebo is a suspension for subcutaneous injection. Placebo is provided in single-use vials. Dosage: aluminium hydroxide (containing 0.5 mg Al3+), in a phosphate buffer. Patients receive 6 doses in 4-week intervals, and then 5 individual booster doses in 3-month intervals, for a total of 11 doses.

Drug: Placebo

Interventions

AADvac1 BIOLOGICAL

AADvac1

Placebo DRUG

Placebo

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 according to the revised National Institute on Aging-Alzheimer's Association (NIA-AA) criteria (McKhann 2011).
• Mini Mental State Examination (MMSE) score ≥ 20 and ≤ 26.
• Brain MRI finding consistent with the diagnosis of Alzheimer's disease
• Medial temporal lobe atrophy: Scheltens score of ≥ 2 (on a scale of 0-4 on the more atrophied side) AND/OR positive AD biomarker profile in the CSF (amyloid+, tau+)
• At least 6 years of formal elementary education.
• Age 50-85 years.
• Fluency in the local language and sufficient auditory and visual capacities to allow neuropsychological testing.
• Ability to read and understand the informed consent.
• Stable therapy with an acetylcholinesterase inhibitor for at least 3 months prior to screening.
• If the patient is on memantine treatment, the dose regimen must be stable for at least 3 months prior to screening.
• Hachinski Ischemia Scale score ≤ 4.
• Availability of a caregiver.
• Female patients must be either surgically sterile or at least 2 years postmenopausal.
• Male patients must either be surgically sterile, or he and his female spouse/partner who is of childbearing potential must be using highly effective contraception starting at screening and continuing throughout the study period.
• Patient provides written informed consent.

You may not qualify if:

• Participation in another clinical study within 3 months prior to screening.
• Pregnant or breastfeeding female.
• Not expected to complete the clinical study.
• Known allergy to components of the vaccine.
• Contraindication for MRI imaging.
• Any of the following detected by brain MRI:
• Infarction in the territory of large vessels
• More than one lacunar infarct.
• Any lacunar infarct in a strategically important location.
• Confluent hemispheric deep white matter lesions (Fazekas grade 3).
• Other focal lesions which may be responsible for the cognitive status of the patient or any other abnormalities associated with significant central nervous disease other than Alzheimer's disease.
• Surgery (under general anaesthesia) within 3 months prior to screening and/or scheduled surgery (under general anaesthesia) during the whole study period.
• Patient has a history and/or currently suffers from a clinically significant autoimmune disease, or is expected to receive immunosuppressive or immunomodulatory treatment at the present or in the future.
• Recent history of cancer (last specific treatment ≤ 5 years prior to Screening).
• Myocardial infarction within 2 years prior to screening.

Sponsors & Collaborators

• Axon Neuroscience SE: lead

Study Sites (42)

Ordination Dr. Bancher

Horn, Lower Austria, 3580, Austria

Location

Universitätsklinik für Neurologie

Graz, Styria, 8036, Austria

Location

Abteilung Psychiatrie und Psychotherapie, LKH Hall

Hall in Tirol, Tyrol, 6060, Austria

Location

Universitätsklinikum Innsbruck

Innsbruck, Tyrol, 6020, Austria

Location

Fakultni nemocnice u sv. Anny v Brne, Mezinarodni centrum klinickeho vyzkumu (ICRC), Centrum pro kognitivni poruchy, Neuro 2

Brno, 656 91, Czechia

Location

Fakultni nemocnice Hradec Kralove, Neurologicka Klinika

Hradec Králové, 500 05, Czechia

Location

Narodni ustav dusevniho zdravi (NÚDZ), Department of cognitive disorders - AD Center

Klecany, 250 67, Czechia

Location

Vseobecna fakultni nemocnice v Praze

Prague, 128 21, Czechia

Location

Fakultni nemocnice v Motole

Prague, 150 06, Czechia

Location

Neuro Centrum Odenwald

Erbach, Rhineland-Palatinate, 64711, Germany

Location

Arzneimittelforschung Leipzig (AFL)

Leipzig, Saxony, 04107, Germany

Location

Universität Heidelberg, Zentralinstitut für Seelische Gesundheit

Mannheim, 68159, Germany

Location

Klinikum rechts der Isar der Technischen Universität München, Klinik und Poliklinik fur Psychiatrie und Psychotherapie

München, 81675, Germany

Location

Praxis Dr. Klaus Christian Steinwachs

Nuremberg, 90402, Germany

Location

Universitätsklinikum Ulm, Klinik und Poliklinik für Neurologie

Ulm, 89081, Germany

Location

Podlaskie Centrum Psychogeriatrii

Bialystok, 15-756, Poland

Location

Pallmed prowadzacy NZOZ Dom Sue Ryder w Bydgoszczy Centrum Psychoneurologii Wieku Podeszlego

Bydgoszcz, 85-796, Poland

Location

Wielospecjalistyczna Poradnia Lekarska Synapsis

Katowice, 40-123, Poland

Location

Care Clinic

Katowice, 40-752, Poland

Location

Centrum Neurologii Klinicznej, Krakowska Akademia Neurologii

Krakow, 31-505, Poland

Location

KO-MED Centra Kliniczne Sp. z o.o.

Lublin, 20-362, Poland

Location

Oddzial Neurologiczny

Olsztyn, 10-082, Poland

Location

NZOZ Neuro-Kard

Poznan, 61-853, Poland

Location

EUROMEDIS Sp. z o.o.

Szczecin, 70-111, Poland

Location

Centrum Medyczne NeuroProtect

Warsaw, 01-697, Poland

Location

Wrocławskie Centrum Alzheimerowskie

Wroclaw, 53-139, Poland

Location

"Dr. Constantin Gorgos" Psychiatry Hospital Titan

Bucharest, 030447, Romania

Location

Neurologicka ambulancia

Banská Bystrica, 974 04, Slovakia

Location

Nestatna psychiatricka ambulancia

Bratislava, 81107, Slovakia

Location

Univerzitna nemocnica Bratislava, Nemocnica Stare Mesto, I. Neurologicka klinika LF UK a UNB

Bratislava, 813 69, Slovakia

Location

Univerzitna nemocnica Bratislava, Psychiatricka klinika LFUK a UNB

Bratislava, 81369, Slovakia

Location

Univerzitna nemocnica L Pasteura Kosice, Psychiatricka klinika

Košice, 041 90, Slovakia

Location

NEURES, s.r.o. Neurologicka ambulancia

Krompachy, 05342, Slovakia

Location

Centrum zdravia R.B.K., s.r.o., Psychiatricka ambulancia

Svidník, 089 01, Slovakia

Location

Pro Mente Sana S.R.O., Psychiatricka Ambulancia

Trenčín, 91108, Slovakia

Location

Fakultna nemocnica s poliklinikou Zilina, Psychiatricke oddelenie

Žilina, 012 07, Slovakia

Location

Univerzitetni klinični Center Ljubljana, Neurology Clinic

Ljubljana, 1000, Slovenia

Location

University Clinical Centre Maribor

Maribor, 2000, Slovenia

Location

Skånes Universitetssjukhus Malmö, Minneskliniken

Malmo, SE-20502, Sweden

Location

Sahlgrenska Universitetssjukhuset, Minnesmottagningen

Mölndal, SE-43141, Sweden

Location

Karolinska Universitetssjukhuset Huddinge

Stockholm, SE-14186, Sweden

Location

Akademiska Sjukhuset I Uppsala, Minnes-och geriatrikmottagningen

Uppsala, SE-75185, Sweden

Location

Related Publications (4)

• Kontsekova E, Zilka N, Kovacech B, Skrabana R, Novak M. Identification of structural determinants on tau protein essential for its pathological function: novel therapeutic target for tau immunotherapy in Alzheimer's disease. Alzheimers Res Ther. 2014 Aug 1;6(4):45. doi: 10.1186/alzrt277. eCollection 2014.

  PMID: 25478018 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Kovacech B, Cullen NC, Novak P, Hanes J, Kontsekova E, Katina S, Parrak V, Fresser M, Vanbrabant J, Feldman HH, Winblad B, Stoops E, Vanmechelen E, Zilka N. Post hoc analysis of ADAMANT, a phase 2 clinical trial of active tau immunotherapy with AADvac1 in patients with Alzheimer's disease, positive for plasma p-tau217. Alzheimers Res Ther. 2024 Nov 23;16(1):254. doi: 10.1186/s13195-024-01620-7.

  PMID: 39580468 DERIVED

MeSH Terms

Conditions

Alzheimer Disease; Frontotemporal Dementia; Motor Activity; Pick Disease of the Brain

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; Behavior

Study Officials

• Reinhold Schmidt, Prof. MD.

  Medical University, Graz, Austria

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: October 9, 2015
• First Posted: October 19, 2015
• Study Start: March 1, 2016
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2019
• Last Updated: November 14, 2019

Record last verified: 2019-11

Locations

AU (4); CZ (5); DE (6); SL (2); SE (4); RO (1); PL (11)