The Alzheimer’s Prevention Initiative ADAD Colombia Trial Program (clinicaltrials.gov NCT06996730) is a new clinical trial that will test the efficacy (as measured by amyloid PET) of the anti-amyloid antibody, donanemab, in autosomal dominant Alzheimer’s disease (ADAD) in the Colombian PSEN1E280A kindred, the world’s largest extended family with ADAD. The study will also explore various ways to maintain low brain amyloid levels using donanemab, a novel gamma secretase modulator, RG6289, or the combination of the two drugs. This two-part clinical trial will include up to 200 cognitively unimpaired or mildly impaired PSEN1 mutation carriers and 40 placebo-treated non-carriers from the E280A kindred.

In Part 1, PSEN1 E280A carriers will receive up to 18 months of an amyloid plaque-clearing antibody, donanemab, treatment, to enable a comparison of the magnitude of Aβ PET and plasma pTau reductions in this ADAD kindred to that observed in trials of the same drug in amyloid positive mildly impaired late onset AD patients and cognitively unimpaired older adults.

In Part 2, carriers will be randomized to receive 1) donanemab maintenance treatment, 2) an oral gamma secretase modulator (GSM) treatment, RG6289, with the potential to minimize the re-accumulation of Aβ aggregates in a complementary, potentially less expensive, and more scalable way, 3) combined donanemab/RG6289 treatment, and 4) placebo treatment for 18 months.