*A Phase 2b Multicentre, Randomised, Double-blind, Placebo-controlled, Parallel Group Dose Finding, Safety, Tolerability and Efficacy Study of PQ912 in Subjects with Mild Cognitive Impairment and Mild Dementia due to Alzheimer*s Disease.*

1. Signed and dated written informed consent obtained from the subject in
accordance with local regulations
2. Male or female, aged >= 50 to <= 80 years
3. A biomarker profile reflecting Alzheimer's Disease (AD), according to the
Alzheimer Association - National Institute on Aging (AA-NIA) Research Framework
[Jack et al 2018] defined as follows:
a) Screening CSF sample with an Aβ42 concentration of <1000 pg/ml AND p-tau >19
pg/ml, or a ratio of p-tau/Aβ42 of >=0.024 as assessed by central laboratory,
(Elecsys assay), OR, in case of subjects in whom CSF sampling is not feasible
due to medical or technical reasons:
b) Existing Positive amyloid Positron-Emission Tomography (PET) evidence within
six months of the screening visit
4. Clinical syndrome of mild cognitive impairment (MCI) or mild dementia
according to the AA-NIA Research Framework [Jack et al 2018]
5. A cognitive impairment in the WAIS-IV Coding Test of at least 0.5 standard
deviations below the normative data
6. Meeting the completion and performance criteria for the Cogstate
Neuropsychological Test Battery (NTB)
7. Be in a stable therapeutic condition with respect to the current AD
condition: either without specific current approved treatment (minimum wash-out
period from a prior treatment is 10 weeks and currently no plan to initiate
currently approved treatment or being on an approved treatment for AD on a
stable dose for at least 10 weeks
8. Fluency in local language and evidence of adequate intellectual functioning
in the opinion of the investigator.
9. Adequate visual and auditory abilities to perform the cognitive and
functional assessments in the opinion of the investigator.
10. Outpatient with study partner capable of accompanying the subject on all
applicable clinic visits.
11. The subject and study partner are likely to be able to participate in all
scheduled evaluations according to country and site practices.

1. Significant neurological or psychiatric disorders, other than AD, that may
affect cognition
2. Atypical clinical presentations of MCI due to AD or mild dementia due to AD,
such as the visual variant of AD (including posterior cortical atrophy),
frontal variant or the language variant (including logopenic aphasia)
3. Moderate and severe dementia with a Mini Mental State Examination (MMSE)
score below 20
4. History of (maximally six months from screening) or screening visit brain
MRI scan indicative of any other significant abnormality, including but not
limited to severe white matter hyperintensities (Fazekas score 3), history or
evidence of a single prior haemorrhage >1 cm3, multiple lacunar infarcts or
evidence of a single prior infarct >1 cm3, evidence of a cerebral contusion,
encephalomalacia, aneurysms, vascular malformations, subdural hematoma, or
space-occupying lesions (e.g. brain tumours)
5. Current presence of a clinically important major psychiatric disorder (e.g.
major depressive disorder) as defined by DSM-5 criteria, or symptom(s) (e.g.
hallucinations) that could affect the subject*s ability to complete the study
6. Current clinically important systemic illness that is likely to result in
clinically relevant deterioration of the subject*s condition or might affect
the subject*s safety during the study
7. History of clinically evident stroke
8. History of seizures within the last two years prior to the screening visit
9. Myocardial infarction within the last six months prior to screening
10. History of cancer within the last two years prior to screening, with the
exception of any of the following conditions: non-metastatic basal cell
carcinoma, and squamous cell carcinoma of the skin. Note: subjects can be
included in the study with a prior history of cancer if evidence of no residual
disease has been clinically confirmed within the last six months before baseline
11. History of uncontrolled hypertension (in the opinion of the investigator)
within six months prior to screening
12. Other clinically important diseases or conditions or abnormalities of vital
signs, physical examination, neurological examination, laboratory results, or
electrocardiogram (ECG) examination (e.g. atrial fibrillation) that could
compromise the study or the safety of the subject
13. Haemoglobin level less than 11 g/dL (6.8 mmol/L) at screening
14. Clinically important infection within 30 days prior to screening e.g.
chronic, persistent, or acute infection, such as bronchitis or urinary tract
infection
15. Known, untreated or insufficiently treated hypothyroidism, vitamin B12 or
folate deficiency
16. Any known hypersensitivity to the investigational product PQ912 or any of
the excipients (section 6.2. of the study protocol)
17. Severe hepatic failure (Child-Pugh C) or kidney failure (creatinine
clearance (eGFR) <= 30 ml/min/1.73m2) as estimated using the MDRD method, or
serum creatinine above 1.5-fold of Upper Limit of Normal (ULN) or
Asparagine-Amino Transferase (AST) or Alanine-Amino Transferase (ALT) above 3
fold of ULN at screening.
18. Blood donation in the 90 days prior to screening
19. History of alcohol or drug dependence or abuse as defined by DSM-5 criteria
within the last two years prior to screening
20. Claustrophobia or presence of pacemakers, aneurysm clips, artificial heart
valves, ear implants, CSF shunts, or metal fragments or foreign objects in the
eyes, skin, or body that would contraindicate a brain MRI scan
21. Inadequate venous access to allow multiple blood draws
22. Personnel involved in the conduct of the study: Subjects who are
investigational site staff members directly involved in the conduct of the
trial and their family members, site staff members otherwise supervised by the
Investigator, or subjects who are Vivoryon employees directly involved in the
conduct of the trial
23. Previous participation in any investigational trial within the last 60 days
of the screening visit
24. of prohibited medications or of measures/ interventions
o Immunosuppressive medications (e.g. systemic corticosteroids in a dose
equivalent to more than 10 mg of prednisolone/day) within the last 90 days
prior to baseline
o Chemotherapeutic agents for malignancy within the last year prior to baseline
o Concomitant treatment which may impair cognitive function requires a wash out
phase of at least 5 half-lives of the treatment prior to screening (short
acting hypnotics are not permitted 72 hours before EEG or cognitive testing)
o Anticoagulants (e.g. heparin, vitamin K antagonists or direct thrombin
inhibitors) within 30 days prior to screening and V8 (week 48)/ EOT. The
combination of clopidogrel and carbasalate calcium or aspirin is not allowed
during the time of lumbar puncture. Clopidogrel or aspirin alone is allowed.
o Strong inhibitors or inducers of CYP2C19: fluconazole, fluvoxamin, ticlopidin
and rifampin (washout phase of at least two weeks before baseline)
o Substrates of CYP2C19 with a narrow therapeutic margin: S mephenytoin,
phenytoin, phenobarbital and indomethacin (washout phase of at least two weeks
before baseline)
o St. John*s Wort (a wash out phase of at least 2 weeks prior to baseline is
required)
25. For women of childbearing potential:
(a) Pregnancy (i.e. positive pregnancy test at Screening) or breastfeeding
(b) Failure to agree to practice a highly effective method of contraception,
from enrolment up to at least 3 months after the study end
26. For sexually active men with a female partner of childbearing potential:
failure to agree to use condom from enrolment up to at least 3 months after the
study end