. 2019 Jun 12;5:216–227. doi: 10.1016/j.trci.2019.02.005

Table 3.

Key inclusion and exclusion criteria for screening in the Generation Program

Inclusion criteria	Exclusion criteria
• Written informed consent, including consent to receive disclosure of APOE genotype: ○ Homozygous APOE4 ○ Or heterozygous APOE4* with elevated brain amyloid (measured by CSF Aβ or amyloid PET) • Male or female, aged 60–75 years inclusive at ICF signature • Females must be postmenopausal • Psychological readiness to receive APOE genotype information based on predisclosure rating scales • Having a study partner • Cognitively unimpaired: ○ MMSE total score ≥24 ○ Score of 85 or greater on the RBANS delayed memory index and CDR global score of 0^†	• Disability that may prevent participant from completing the study (e.g., blindness or deafness) • Current medical or neurological condition that may impact cognitive assessments • Advanced disease that may interfere with study assessments • History of malignancy in past 5 years (with or without treatment) • Indication for or current treatment with cholinesterase inhibitors or other AD treatments • Recent suicidal ideation or past behavior on the eC-SSRS • Use of other investigational drugs prior to screening • Current chronic treatment with strong CYP3A4 inducers (umibecestat only) • Brain MRI results that indicate an abnormality, which might be a leading cause of cognitive decline or hinder MRI assessments • Evidence of amyloid-related imaging abnormality including hemorrhages (CAD106 in Generation Study 1 only) • Positive drug screen due to drug abuse or dependence • Clinically significant ECG findings • Prior treatment with drugs known for their potential to cause major organ system toxicity • Contraindication or intolerance to PET or MRI • If PET scans are scheduled: total dosimetry above acceptable exposure • If CSF sampling is scheduled: contraindication to lumbar puncture

Inclusion criteria

Exclusion criteria

•
Written informed consent, including consent to receive disclosure of APOE genotype:
- ○
  Homozygous APOE4
- ○
  Or heterozygous APOE4* with elevated brain amyloid (measured by CSF Aβ or amyloid PET)
•
Male or female, aged 60–75 years inclusive at ICF signature
•
Females must be postmenopausal
•
Psychological readiness to receive APOE genotype information based on predisclosure rating scales
•
Having a study partner
•
Cognitively unimpaired:
- ○
  MMSE total score ≥24
- ○
  Score of 85 or greater on the RBANS delayed memory index and CDR global score of 0^†

•
Disability that may prevent participant from completing the study (e.g., blindness or deafness)
•
Current medical or neurological condition that may impact cognitive assessments
•
Advanced disease that may interfere with study assessments
•
History of malignancy in past 5 years (with or without treatment)
•
Indication for or current treatment with cholinesterase inhibitors or other AD treatments
•
Recent suicidal ideation or past behavior on the eC-SSRS
•
Use of other investigational drugs prior to screening
•
Current chronic treatment with strong CYP3A4 inducers (umibecestat only)
•
Brain MRI results that indicate an abnormality, which might be a leading cause of cognitive decline or hinder MRI assessments
•
Evidence of amyloid-related imaging abnormality including hemorrhages (CAD106 in Generation Study 1 only)
•
Positive drug screen due to drug abuse or dependence
•
Clinically significant ECG findings
•
Prior treatment with drugs known for their potential to cause major organ system toxicity
•
Contraindication or intolerance to PET or MRI
•
If PET scans are scheduled: total dosimetry above acceptable exposure
•
If CSF sampling is scheduled: contraindication to lumbar puncture

NOTE. *Generation Study 2 only; ^†If the RBANS delayed memory index score is between 70 and 84 (inclusive) and the global CDR score = 0, the participant may be allowed to continue only if the investigator judges that cognition is unimpaired following review of the MCI/dementia criteria. If the global CDR score = 0.5 and the RBANS delayed memory index score is 85 or greater, the participant may be allowed to continue only if the investigator judges that cognition is unimpaired following review of the MCI/dementia criteria.

Abbreviations: Aβ, amyloid beta; AD, Alzheimer's disease; CDR, Clinical Dementia Rating; CSF, cerebrospinal fluid; C-SSRS, Columbia–Suicide Severity Rating Scale; ECG, electrocardiogram; eC-SSRS, electronic C-SSRS; MCI, mild cognitive impairment; MMSE, Mini-Mental State Examination; MRI, magnetic resonance imaging; PET, positron emission tomography; RBANS, Repeatable Battery for the Assessment of Neuropsychological Status; homozygous, APOE ε4/ε4; heterozygous, APOE ε2/ε4 or ε3/ε4.