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

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: 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).