The Alzheimer’s Prevention Initiative (API) Autosomal Dominant Alzheimer’s Disease (ADAD) Colombia Trial (clinicaltrials.gov NCT01998841) was a randomized, placebo-controlled clinical trial of the anti-oligomeric amyloid-β (Aβ) monoclonal antibody treatment crenezumab in 252 cognitively unimpaired Colombian PSEN1 E280A mutation carriers and non-carriers from the world’s largest ADAD kindred (API-Colombia). The mutation carriers are virtually certain to develop Alzheimer’s disease and progress to mild cognitive impairment (MCI) and dementia at the respective median ages of 44 and 49. Like other ADAD mutation carriers, PSEN1 E280A mutation carriers demonstrate biomarker evidence of amyloid-β (Aβ) plaque more than 25 years before the onset of dementia, followed by tau tangle deposition and neurodegeneration. The API ADAD Trial included participants within about 15 years from carriers’ median age of MCI onset at the time of enrollment and who had not received information about their genetic risk, who received 60-96 months of double-blind treatment utilizing a common close design.

This study consisted of two periods:

1. Study Period A – evaluating the efficacy and safety of crenezumab versus placebo in participants who carry the PSEN1 E280A autosomal-dominant mutation and did not meet the criteria for mild cognitive impairment due to Alzheimer’s or dementia due to Alzheimer’s and were thus, in a preclinical phase of Alzheimer’s. Participants were randomized in a 1:1 ratio to receive either crenezumab or placebo subcutaneously (every 2 weeks) or intravenously (every 4 weeks) for at least 260 weeks. A cohort of participants (non-mutation carriers) were also enrolled and were dosed solely on placebo
2. Study Period B – Participants were offered the opportunity to continue to receive study drug until the results of the study were known and post-trial access to crenezumab was started or development of crenezumab was discontinued.