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Table 1 Inclusion and exclusion criteria

From: Rationale and study design of a randomized, placebo-controlled, double-blind phase 2b trial to evaluate efficacy, safety, and tolerability of an oral glutaminyl cyclase inhibitor varoglutamstat (PQ912) in study participants with MCI and mild AD—VIVIAD

• Principal inclusion criteria
- Male or female, aged ≥ 50 to ≤ 80 years
- A biomarker profile reflecting AD, according to the Alzheimer Association—National Institute on Aging (AA-NIA) Research Framework (Jack et al. 2018) defined as follows:
o a1) Screening CSF sample with an Aβ42 concentration of < 1000 pg/ml AND p-tau > 19 pg/ml, OR
o a2) A ratio of p-tau/Aβ42 of ≥0.024 as assessed by central laboratory, (Elecsys assay), OR, in case of study participants in whom CSF sampling is not feasible due to medical or technical reasons.
o b) Existing positive amyloid positron-emission tomography (PET) evidence within 6 months of the screening visit
- Clinical syndrome of MCI or mild dementia according to the AA-NIA Research Framework (Jack et al. 2018)
- Signed and dated written informed consent obtained from the subject in accordance with local regulations
- A cognitive impairment in the digital symbol substitution test (DSST ) of at least one standard deviation below the normative data
- Being in a stable condition with respect to the current AD condition: either without specific treatment or in a stable dose of AD medication for the past 10 weeks
- Outpatient with study partner capable of accompanying the subject on screening visits, week 24, 48 weeks, and at the end of treatment visit (EOT)
Principal exclusion criteria
- Significant neurological or psychiatric disorders other than AD that may affect cognition
- Atypical prenstations of MCI due to AD or mild dementia due to AD (such as posterior cortical atrophy, frontal variant, or language variant)
- Moderate and severe dementia with a MMSE below 20
- History of (maximally 6 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 hemorrhage > 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 tumors)
- 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
- History of stroke or seizures
- Myocardial infarction within 6 months of screening
- History of cancer within the past 2 years prior to screening (except: non-metastatic basal cell carcinoma, and squamous cell carcinoma of the skin) OR no signs of residual cancer confirmed minimum 6 months before baseline
- History of uncontrolled hypertension within 6 months prior to baseline
- Hemoglobin level less than 11 g/dL at screening
- Clinically important infections within 30 days prior to screening
- Insufficiently or untreated hypothyroidism, B12 or folate deficiency
- Severe hepatic failure (Child-Pugh C) or kidney failure (creatinine clearance (eGFR) ≤ 30 mL/min/1.73 m2) 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.