Increased flexibility in the timing of the first lumbar puncture for cerebrospinal fluid (CSF) sample collection. Change in fasting requirements for laboratory assessments: no fasting requirements for blood sample collection, except for screening.

Amendment of eligibility criteria, which would allow subjects to roll over to an open-label extension study. A requirement for additional safety assessments at 8- and 12-weeks was added for those subjects, who discontinue prematurely from the study. Allow nurse practitioners and equivalently qualified personnel (under applicable law) to review and sign-off on the Mini-Mental State Examination (MMSE) and the Columbia-Suicide Severity Scale (C-SSRS) before the subject is discharged. Allow collection of PK samples 60−90 minutes post infusion. To clarify that start or discontinuation of an approved Alzheimer's Disease (AD) treatment or dose changes of approved AD treatments during the study are in principle not permitted. Crenezumab has been introduced as an alternative name for MABT5012A.

The included and excluded concomitant medications at screening and throughout the duration of the study were clarified: soporifics are allowed if administered at a stable dose prior to randomization and throughout the study, opiates and opioids are prohibited if administered chronically; intermittent use of soporifics, opiates, opioids and benzodiazepines is allowed except 5 half-lives prior to neurocognitive assessment. The protocol has been updated to reflect the correct weight to use for intravenous (IV) dose calculations, specifically, that the subject’s screening weight (reference weight) will be used at each visit, unless the current weight has changed (increase or decrease) by >= 10% from the screening weight (or the last reference weight used). If this occurs, the current weight will become the reference weight for subsequent dosing.

The interim analysis plan was modified to synchronize more closely with the companion trial (Study ABE4869g/GN00761): two interim analyses will be conducted: one after all subjects in both the subcutaneous (SC) and intravenous (IV) cohorts have completed the week 49 assessment and another after all subjects in the SC cohort have completed the week 73 assessment. Restriction on analysis of cognitive endpoints if Alzheimer’s disease (AD) medications were changed while subjects are on study, was eliminated.