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Status unknownNCT03174886AIDAUpdated Nov 14, 2019

A 24-month Phase 1 Pilot Study of AADvac1 in Patients With Non Fluent Primary Progressive Aphasia

A Phase 1 interventional study of AADvac1 40 µg and AADvac1 160 µg in Primary Progressive Nonfluent Aphasia, sponsored by Axon Neuroscience SE. Status unknown at 3 sites in Germany. Open to participants aged 18 Years to 85 Years. Per ClinicalTrials.gov, last updated 2019-11-14.

Sponsored by Axon Neuroscience SE · Phase 1, Interventional, and Treatment

The sponsor has not verified this record recently (last verified Nov 2019), so the status shown — last known as Active, not recruiting — may be out of date.
Phase
Phase 1
Study type
Interventional
Enrollment
33
Allocation
Randomized
Ages
18 Years to 85 Years
Sex
All
01

Study summary

This study is a pilot trial evaluating the safety and immunogenicity of AADvac1 in patients with the non-fluent variant of Primary Progressive Aphasia.

50% of participants will receive the 40 µg dosage of AADvac1 and 50% of participants will receive the 160 µg dosage of AADvac1. No placebo is used.

Read the detailed description

The non-fluent variant of Primary progressive Aphasia (nfvPPA) 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.

No treatments are currently available; symptomatic medications are used off-label in nfvPPA.

AADvac1 is designed to raise antibodies against pathological tau protein (the primary constituent of neurofibrillary pathology, which is the underlying cause of disease in \~80% of nfvPPA cases). 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.

02

Conditions studied

  • Primary Progressive Nonfluent Aphasia

Keywords

  • tau
  • neurofibrillary
  • degeneration
  • primary progressive aphasia
  • agrammatic
  • tauopathy
  • immunotherapy
  • immunization
03

In context

Aphasia

365 studies on the registry are indexed under Aphasia; 89 are open to participants now.

This study's enrollment of 33 is close to the median of 30 across 316 interventional studies indexed under Aphasia.

Browse Aphasia studies →

Lead sponsor

Axon Neuroscience SE is the lead sponsor of 4 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 85 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Patient has a clinical diagnosis of non-fluent/agrammatic variant PPA according to the criteria by Gorno-Tempini et al. (2011) with evidence of left frontal brain hypometabolism. Patients with right-sided hypometabolism are eligible for the study only if they are left-handed.
  2. Patient has a FTLD-CDR language domain score of ≤ 2, and other individual FTLD-CDR domain scores ≤ 1.
  3. Patient's age is 18 - 85 years inclusive at the time of having provided informed consent.
  4. Patient has adequate visual and auditory abilities and premorbid local language skills to allow neuropsychological testing.
  5. Sexually active female patients must be using highly effective contraception methods, or be surgically sterile, or be at least 2 years post-menopausal.
  6. Sexually active male patients must be using highly effective contraception methods, or be surgically sterile.
  7. Patient and caregiver have signed and dated written informed consent.
  8. Availability of a partner/caregiver knowing the patient and being able to accompany the patient to the visits.
  9. Patient is legally competent.

Exclusion criteria

Exclusion Criteria:

  1. The patient's brain MRI is incompatible with a diagnosis of nfvPPA.
  2. Patient has a history or evidence of a central nervous system (CNS) disorder other than nfvPPA which may cause symptoms of aphasia or dementia (Alzheimer's disease, Dementia with Lewy Bodies, inflammatory/demyelinating CNS conditions, Creutzfeldt-Jakob disease, Huntington's disease, etc.)
  3. Patient has a history or currently suffers from a significant psychiatric illness such as schizophrenia, any type of psychotic disorder or bipolar affective disorder.
  4. Patient has a history or evidence of cerebrovascular disease (ischemic or haemorrhagic stroke), or diagnosis of possible, probable or definite vascular dementia.
  5. Patient has Wernicke's encephalopathy.
  6. Patient has metabolic or toxic encephalopathy or dementia due to a general medical condition.
  7. Patient suffers from hypothyroidism, defined as 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 12 weeks before study entry.
  8. Patient has a known pathogenic mutation in GRN or C9orf72.
  9. Presence or history of allergy to components of the vaccine.
  10. Presence and/or history of immunodeficiency (e.g., HIV).
  11. Patient is currently being treated with immunosuppressive drugs.
  12. 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.
  13. Patient has a recent (≤ 5 years since last specific treatment) history of cancer (Exceptions: basal cell carcinoma, intraepithelial cervical neoplasia).
  14. Patient has an active infectious disease (e.g., Hepatitis B, C).
  15. Patient had a myocardial infarction within the last 2 years.

  16. Patient has a current clinically important systemic illness that is likely to result in deterioration of the patient's condition or affect the subject's safety during the study:

    1. poorly controlled congestive heart failure (New York Heart Association [NYHA] score ≥ 3),
    2. poorly controlled diabetes,
    3. severe renal insufficiency (Estimated glomerular filtration rate \< 30 mL/min),
    4. chronic liver disease - ALT (alanine aminotransferase) > 2x upper limit of normal range (ULN), AST (aspartate aminotransferase) > 2x ULN
    5. other clinically significant systemic illness, if considered relevant by the investigator.
  17. Patient had alcohol or drug dependence within the past year.
  18. Patient has a current diagnosis of epilepsy.
  19. Pregnant or breastfeeding women.
  20. Patient has participated in another interventional clinical trial within 12 weeks before Visit 01.
  21. Patient has contraindication for MRI imaging such as metallic endoprosthesis or MRI-incompatible stent implantation.
  22. Patient has contraindications for other study procedures, such as CSF sampling.
  23. Patient had surgery (under general anaesthesia) within 12 weeks prior to Visit 01 and/or scheduled surgery (under general anaesthesia) during the whole study period.
  24. Patient is currently being treated or was treated in the past with any active vaccines for a neurodegenerative disorder.
  25. Patients not expected to complete the clinical trial.
  26. Patient, in the opinion of the investigator, is unlikely to comply with the clinical study protocol, or is unsuitable for other reasons.
  27. Patient is dependent from Sponsor or investigator (e.g. as an employee or as a relative).
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Participant)
Enrollment
33 participants (actual)

Study arms

  • Experimental
    AADvac1 40 µg

    The intervention consists of Axon Peptide 108 coupled to keyhole limpet haemocyanin (KLH) 40 µg/0.30 mL suspension for injection; and aluminium hydroxide Al(OH)3 (containing approx. 0.5 mg Al3+/0.30 mL), administered subcutaneously. The basic immunisation regimen consists of 6 doses administered subcutaneously in 6-week intervals. Subsequently, 5 booster doses are applied in 13-week intervals, for a total of 11 administrations.

    Drug: AADvac1 40 µg

  • Experimental
    AADvac1 160 µg

    The intervention consists of Axon Peptide 108 coupled to KLH 160 µg/0.30 mL suspension for injection; and aluminium hydroxide Al(OH)3 (containing approx. 0.5 mg Al3+/0.30 mL), administered subcutaneously. The basic immunisation regimen consists of 6 doses administered subcutaneously in 6-week intervals. Subsequently, 5 booster doses are applied in 13-week intervals, for a total of 11 administrations.

    Drug: AADvac1 160 µg

Interventions

  • DrugAADvac1 40 µg

    Active immunotherapy against neurofibrillary pathology.

  • DrugAADvac1 160 µg

    Active immunotherapy against neurofibrillary pathology.

06

What researchers measure

Primary outcomes

  1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

    The safety assessment is based on the number, type and severity of adverse events (AEs).

    Time frame: 25 months

  2. Immunogenicity (Percentage of patients who develop an IgG immune response, geometric mean titre of titre of antibodies against Axon Peptide 108, IgG to IgM ratio of antibodies against Axon Peptide 108)

    AADvac1 depends on raising antibodies that mediate its treatment effects. Immunogenicity assessment includes: Percentage of AADvac1-treated patients who develop an immune response (responder rate), geometric mean titre of antibodies against Axon Peptide 108, IgG to IgM ratio of antibodies against Axon Peptide 108.

    Time frame: 24 months

Other outcomes

  1. Cerebrospinal fluid (CSF) biomarkers

    Temporal change in total CSF neurogranin, phosphorylated neurofilament heavy chain protein, ubiquitin, β-synuclein, tau protein, phospho-tau pT181, N-terminal tau protein, amyloid β1-40, amyloid-β1-42, ubiquitin, α-, β- and γ-synuclein, Chitinase-3-like protein (YKL-40), Monocyte chemoattractant protein-1 (MCP-1), and other CSF markers

    Time frame: 24 months

  2. Serum neurofilament light chain protein (and other blood biomarkers of nfvPPA)

    Temporal change in neurofilament light chain protein and other blood biomarkers (exploratory measure; biomarker panel to be finalised based on the state of the art at the time of analysis)

    Time frame: 24 months

  3. Magnetic resonance imaging (MRI) volumetry

    Temporal change in whole brain volume and set of regions of interest, as measured by MRI

    Time frame: 24 months

  4. Frontotemporal lobar degeneration - Clinical Dementia Rating - Sum of Boxes (FTLD-CDR-SB)

    Temporal change in FTLD-CDR SB score

    Time frame: 24 months

  5. Clinician's Global Impression - Improvement (CGI-I)

    Temporal change in CGI-I score

    Time frame: 24 months

  6. Instrumental Activities of Daily Living (IADL)

    Temporal change in Amsterdam IADL

    Time frame: 24 months

  7. Custom Cognitive Battery

    Temporal change in the custom Cognitive Battery score

    Time frame: 24 months

  8. Addenbrooke's Cognitive Examination

    Temporal change in Addenbrooke's Cognitive Examination score

    Time frame: 24 months

  9. Unified Parkinson's disease rating scale (UPDRS) part III

    Temporal change in UPDRS part III score

    Time frame: 24 months

  10. Frontal Systems Behavior Scale (FrSBe)

    Temporal change in FrSBe score

    Time frame: 24 months

  11. Immune cell (granulocyte, monocyte, and lymphocyte populations)

    Temporal change in immunological variables (monocytes, lymphocytes, basophil and neutrophil granulocytes; a range of lymphocyte sub-populations - CD3+, CD3+/CD4+, CD3+/CD4+/CD28+, CD3+/CD4+/CD28+/CD45RA+, CD3+/CD4+/CD28+/CD45RO+, CD3+/CD8+, CD3+/CD8+/CD28+, CD3+/CD8+/CD28+/CD45RA+, CD3+/CD8+/CD28+/CD45RO+) over 24 months

    Time frame: 24 months

  12. Correlation of a range of potential immunological predictors with IgG antibody titres against Axon Peptide 108

    Correlation of measures of immune response with immunological variables (monocytes, lymphocytes, basophil and neutrophil granulocytes; a range of lymphocyte sub-populations - CD3+, CD3+/CD4+, CD3+/CD4+/CD28+, CD3+/CD4+/CD28+/CD45RA+, CD3+/CD4+/CD28+/CD45RO+, CD3+/CD8+, CD3+/CD8+/CD28+, CD3+/CD8+/CD28+/CD45RA+, CD3+/CD8+/CD28+/CD45RO+) will individually be assessed for correlation with IgG antibody titres. The possibility of multiple independent predictors of the antibody response will be examined using regression trees analysis)

    Time frame: 24 months

07

Study locations

3 sites
  • Universitätsmedizin Göttingen, Klinik für Psychiatrie und Psychotherapie
    Göttingen, 37075, Germany
  • Klinikum Rechts der Isar der TU München, Klinik und Poliklinik für Psychiatrie und Psychotherapie
    München, 81675, Germany
  • Universitätsklinikum Ulm
    Ulm, 89081, Germany
08

References and documents

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 ↗

Individual participant data

Plan to share: Undecided

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 14, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT03174886
Lead sponsor
Axon Neuroscience SE
Responsible party
Sponsor
First posted
Jun 5, 2017
Start date
Jul 31, 2017
Primary completion
Nov 2020 (estimated)
Completion
Nov 2020 (estimated)
Last update
Nov 14, 2019

Study contacts

Markus Otto, Prof
principal investigator · Universitat Ulm

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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