Table 2.

Key study objectives for the Generation Program

Objectives
Primary objective •To demonstrate the effects of CAD106 and umibecestat* versus placebo on TTE, with event defined as a diagnosis of MCI due to AD or dementia due to AD, whichever occurs first during the course of the study •To demonstrate the effects of CAD106 and umibecestat versus respective placebo on cognition as measured by the change from the baseline to month 60 in the APCC test score
Secondary objectives •To assess the effects of CAD106 and umibecestat versus placebo on global clinical status as measured by the change from the baseline to month 60 in CDR-SOB score •To assess the safety and tolerability of CAD106 and umibecestat versus placebo as measured by AEs, changes in brain structural MRI, laboratory tests, and noncognitive neurological examinations •To demonstrate treatment effects on cognition and function using RBANS and ECog •To demonstrate treatment effects on biomarkers including amyloid/tau pathology, and brain atrophy (CSF and brain imaging)
Exploratory objectives •To assess impact of disclosure and psychiatric symptoms of the disease with psychiatric evaluations •To assess health-related quality of life and changes in lifestyle •To assess additional imaging biomarkers, CSF and blood-based samples

NOTE. *Generation Study 2 investigates the use of umibecestat versus placebo only; Control: Generation Study 1 matching placebo group, Generation Study 2 placebo group.

Abbreviations: AD, Alzheimer's disease; AE, adverse event; APCC, API preclinical composite cognitive battery; API, Alzheimer's Prevention Initiative; CDR-SOB, Clinical Dementia Rating Scale Sum of Boxes; CSF, cerebrospinal fluid; ECog, Everyday Cognition Scale; MCI, mild cognitive impairment; MRI, magnetic resonance imaging; RBANS, Repeatable Battery for the Assessment of Neuropsychological Status; TTE, time to event.