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Alzheimer's DiseasePhase 2ADAMANTNCT02579252

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

A Phase 2 study testing AADvac1 in people with Alzheimer's Disease, run by Axon Neuroscience SE at 42 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 50 to 85 years
Conditions the study is for
Alzheimer's Disease
What is being tested?
AADvac1
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
208 participants
Where
42 sitesin 8 countries
Study dates
Mar 2016to Jun 2019
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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:
Show all 41Show fewer
  • 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.
  • Hepatitis B, C, HIV or Syphilis.
  • Active infectious disease.
  • Presence and/or history of immunodeficiency.
  • Patient currently suffering from a clinically important systemic illness:
  • poorly controlled congestive heart failure (NYHA ≥ 3)
  • BMI > 40
  • poorly controlled diabetes (HbA1c > 7.5%)
  • severe renal insufficiency (eGFR < 30 mL/min)
  • chronic liver disease - ALT (alanine aminotransferase) > 66 U/L in females or > 80 U/L in males, AST (aspartate aminotransferase) > 82 U/L
  • QTc interval prolongation in ECG (> 450 ms)
  • other clinically significant systemic illness, if considered relevant by the investigator
  • Hypothyroidism, defined as TSH (thyroid-stimulating hormone) elevation > 5.000 mcIU/mL, and/or FT4 levels < 0.7 ng/dL. Patients with corrected hypothyroidism are eligible for the study provided that treatment has been stable for 3 months before study entry.
  • Valid diagnosis of a significant psychiatric illness such as schizophrenia, any type of psychotic disorder or bipolar affective disorder.
  • Current depressive episode (Geriatric Depression Scale GDS ≥ 6) or major depressive episode within the last 1 years.
  • Metabolic or toxic encephalopathy or dementia due to a general medical condition.
  • History of alcohol or drug abuse or dependence within the past 2 years.
  • Wernicke's encephalopathy.
  • History or evidence of any CNS disorder other than AD that could be the cause of dementia.
  • Cerebrovascular disease (ischemic or haemorrhagic stroke), or diagnosis of possible, probable or definite vascular dementia.
  • Epilepsy.
  • Treatment with experimental immunotherapeutics including intravenous immunoglobulin within 3 months prior to screening.
  • Treatment with experimental therapies for AD aiming at disease-modification within 3 months prior to screening.
  • Patient is currently being treated or was treated in the past with any active vaccines for AD.
  • Treatment with immunosuppressive drugs.
  • Change in dose of previous and current medications within the last 30 days prior to Screening (V01), if considered clinically relevant by the investigator.
  • Vitamin B12 deficiency (serum vitamin B12 < 191 pg/mL).

Trial locations and contacts

42 sites in 8 countries.

42 sites in 8 countries

Poland11 sites

  • Podlaskie Centrum Psychogeriatrii

    Bialystok, 15-756

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

    Bydgoszcz, 85-796

  • Wielospecjalistyczna Poradnia Lekarska Synapsis

    Katowice, 40-123

  • Care Clinic

    Katowice, 40-752

  • Centrum Neurologii Klinicznej, Krakowska Akademia Neurologii

    Krakow, 31-505

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

    Lublin, 20-362

  • Oddzial Neurologiczny

    Olsztyn, 10-082

  • NZOZ Neuro-Kard

    Poznan, 61-853

  • EUROMEDIS Sp. z o.o.

    Szczecin, 70-111

  • Centrum Medyczne NeuroProtect

    Warsaw, 01-697

  • Wrocławskie Centrum Alzheimerowskie

    Wroclaw, 53-139

Other trials in Poland

Slovakia9 sites

  • Neurologicka ambulancia

    Banská Bystrica, 974 04

  • Nestatna psychiatricka ambulancia

    Bratislava, 81107

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

    Bratislava, 813 69

  • Univerzitna nemocnica Bratislava, Psychiatricka klinika LFUK a UNB

    Bratislava, 81369

  • Univerzitna nemocnica L Pasteura Kosice, Psychiatricka klinika

    Košice, 041 90

  • NEURES, s.r.o. Neurologicka ambulancia

    Krompachy, 05342

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

    Svidník, 089 01

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

    Trenčín, 91108

  • Fakultna nemocnica s poliklinikou Zilina, Psychiatricke oddelenie

    Žilina, 012 07

Other trials in Slovakia

Germany6 sites

  • Neuro Centrum Odenwald

    Erbach, Rhineland-Palatinate, 64711

  • Arzneimittelforschung Leipzig (AFL)

    Leipzig, Saxony, 04107

  • Universität Heidelberg, Zentralinstitut für Seelische Gesundheit

    Mannheim, 68159

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

    München, 81675

  • Praxis Dr. Klaus Christian Steinwachs

    Nuremberg, 90402

  • Universitätsklinikum Ulm, Klinik und Poliklinik für Neurologie

    Ulm, 89081

Other trials in Germany

Czechia5 sites

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

    Brno, 656 91

  • Fakultni nemocnice Hradec Kralove, Neurologicka Klinika

    Hradec Králové, 500 05

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

    Klecany, 250 67

  • Vseobecna fakultni nemocnice v Praze

    Prague, 128 21

  • Fakultni nemocnice v Motole

    Prague, 150 06

Other trials in Czechia

Austria4 sites

  • Universitätsklinik für Neurologie

    Graz, Styria, 8036

  • Abteilung Psychiatrie und Psychotherapie, LKH Hall

    Hall in Tirol, Tyrol, 6060

  • Ordination Dr. Bancher

    Horn, Lower Austria, 3580

  • Universitätsklinikum Innsbruck

    Innsbruck, Tyrol, 6020

Other trials in Austria

Sweden4 sites

  • Skånes Universitetssjukhus Malmö, Minneskliniken

    Malmö, SE-20502

  • Sahlgrenska Universitetssjukhuset, Minnesmottagningen

    Mölndal, SE-43141

  • Karolinska Universitetssjukhuset Huddinge

    Stockholm, SE-14186

  • Akademiska Sjukhuset I Uppsala, Minnes-och geriatrikmottagningen

    Uppsala, SE-75185

Other trials in Sweden

Slovenia2 sites

  • Univerzitetni klinični Center Ljubljana, Neurology Clinic

    Ljubljana, 1000

  • University Clinical Centre Maribor

    Maribor, 2000

Other trials in Slovenia

Romania1 site

  • "Dr. Constantin Gorgos" Psychiatry Hospital Titan

    Bucharest, 030447

Other trials in Romania

About this study

Official title: A 24 Months Randomised, Placebo-controlled, Parallel Group, Double Blinded, Multi Centre, Phase 2 Study to Assess Safety and Efficacy of AADvac1 Applied to Patients With Mild Alzheimer's Disease

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.

Read the detailed description

Alzheimer's disease (AD) is a chronic progressive neurodegenerative disorder of the brain. Over the course of the disease, pathological proteins accumulate in the brain, damaging neurons, thus causing them to lose their connections and die.

Currently available treatments are designed to compensate for the neurotransmitter loss caused by the disease without affecting the disease process itself.

AADvac1 is designed to raise antibodies against pathological tau protein (the primary constituent of neurofibrillary pathology in AD). These antibodies are expected to prevent tau protein from aggregating, to facilitate the removal of tau protein aggregates and prevent the spreading of pathology, slowing or halting the progress of the disease.

Being tested
AADvac1, Placebo
Keywords
vaccine, tau protein, active, immunization, KLH, immunotherapy, tau
Medical subject headings
Alzheimer Disease, Frontotemporal Dementia, Motor Activity, Pick Disease of the Brain

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AADvac1Biological

  • PlaceboDrug

Study groups in NCT02579252
Study groupRoleWhat they receive
AADvac1ExperimentalAADvac1 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.
Receives: Biological: AADvac1
PlaceboPlacebo comparatorPlacebo 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.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 24 months

Secondary outcomes (4)

  1. Clinical Dementia Rating (CDR) Sum of Boxes

    The domain scores of the standard 6-domain CDR assessment will be summed up to obtain a Sum-of-Boxes score of 0-18

    Measured: 24 months

  2. Custom cognitive battery (composite standard score)

    A composite standard score will be calculated from the following tests:

    Cogstate International Shopping List Task (memory)

    • immediate free recall
    • delayed free recall
    • delayed recognition

    Cogstate One Card Learning Task (memory)

    Cogstate One Card Back Task (memory)

    Category Fluency Test (executive function, language)

    Letter Fluency Test (executive function, language)

    Digit Symbol Coding (executive functioning, working memory and processing speed)

    Measured: 24 months

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

    Activities of daily living will be assessed using the informant-based ADCS questionnaire (both the score for the 18-point and the 24-point version will be calculated)

    Measured: 24 months

  4. Immunogenicity

    Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Oct 2015 (estimated)
  2. Study startMar 2016
  3. Primary completionJun 2019
  4. Study completionJun 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
208 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02579252
Sponsor's protocol ID
AC-AD-003
Other IDs
2015-000630-30, 2015
Acronym
ADAMANT
Status last verified
Nov 2019
First submitted
9 Oct 2015
Last updated
14 Nov 2019
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 25478018

  • 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.

    PubMed 25478017

  • 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.

    PubMed 27955995

  • 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.

    PubMed 39580468

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing AADvac1 in people with Alzheimer's Disease, run by Axon Neuroscience SE at 42 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 41 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 42 sites in Poland, Slovakia, Germany, Czechia, Austria and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety (all-case treatment-emergent adverse events except local reactions) (time frame: 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02579252, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2019.

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