A Study of Crenezumab Versus Placebo in Preclinical Presenilin1 (PSEN1) E280A Mutation Carriers to Evaluate Efficacy and Safety in the Treatment of Autosomal-Dominant Alzheimer's Disease (AD), Including a Placebo-Treated Non-Carrier Cohort

This study consists of 2 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 do not meet the criteria for mild cognitive impairment due to AD or dementia due to AD and are thus, in a preclinical phase of AD. Participants will be randomised 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) will also be enrolled and will be dosed solely on Placebo and \[2\] Study Period B - Participants will be offered the opportunity to continue to receive study drug until the results of the study are known and post trial access to Crenezumab is started or development of Crenezumab is discontinued.

• Period A: Annualized Rate of Change in the Autosomal-Dominant Alzheimer's Disease (API ADAD) Composite Cognitive Test Total Score
• Period A: Annualized Rate of Change in an Episodic Memory Measure: Free and Cued Selective Reminding Task (FCSRT) Cueing Index

1. Last registry update

   Jul 30, 2024

2. Results first posted

   Sep 22, 2023

3. Study completion

   Aug 8, 2023

4. Primary completion

   Mar 22, 2022

5. Started

   Dec 20, 2013

6. Registered

   Dec 2, 2013

• Baseline and placebo-related imaging, cerebrospinal fluid, plasma biomarker, and cognitive findings in unimpaired PSEN1 E280A mutation carriers and non-carriers in the Alzheimer's Prevention Initiative Autosomal Dominant Alzheimer's Disease Colombia Trial

  EBioMedicine