Exploratory evaluation of 18F‐MK‐6240 tau PET positivity in TANGO phase 2 clinical trial of gosuranemab (BIIB092) in Mild Cognitive Impairment and mild Alzheimer’s disease

Abstract

AbstractBackgroundTANGO was a randomized, placebo‐controlled, phase 2 study evaluating gosuranemab, an investigational anti‐tau antibody, for potential treatment of mild cognitive impairment (MCI) due to Alzheimer’s disease and mild Alzheimer’s disease. We explored the feasibility and validity of assessing 18F‐MK‐6240 tau PET positivity in post hoc exploratory analyses, to inform evaluation of treatment effect in future clinical trials.MethodTANGO enrolled 654 individuals aged 50‐80 years, diagnosed with MCI due to Alzheimer’s disease or mild Alzheimer’s disease, positive for amyloid pathology. 357 participants enrolled in an optional 18F‐MK‐6240 tau PET substudy. Two expert neuroradiologists read each baseline scan as visually tau positive (Tau+) or negative (Tau‐); discrepant cases were resolved by consensus. Exploratory regional SUVR quantitative thresholds (>2 standard deviations from the mean) were derived on an external 18F‐MK‐6240 sample of N=103 elderly, cognitively unimpaired, amyloid negative adults. TANGO baseline tau PET scans were classified as quantitatively Tau+ if SUVR was above a threshold in composite regions for Braak I‐II (SUVR >1.22) and/or Braak III‐IV (SUVR > 1.29). Baseline demographics and clinical characteristics were compared between the Tau+ and Tau‐ groups and concordance between the two tau positivity approaches (visual read vs. quantitative SUVR thresholds) was assessed.Results85%‐90% of the TANGO tau PET substudy population was Tau+ at baseline using quantitative or visual read approaches, respectively. Interrater agreement for the two visual readers was high (97%). Agreement between the visual read and quantitative methods was also high (93%). Tau+ and Tau‐ groups overlapped in their baseline clinical and demographic characteristics, but the Tau+ group trended toward indicators of more advanced disease at baseline (e.g. worse clinical scores).ConclusionsBased on this study of patients diagnosed with MCI due to AD and mild Alzheimer’s disease, patients who are amyloid positive also have a high probability of having tau pathology as measured by either visual read or quantitative assessment. These exploratory analyses suggest the criteria for 18F‐MK‐6240 tau PET positivity using either visual read or SUVR quantitative thresholds are feasible and valid and provides opportunities to incorporate evaluation of 18F‐MK‐6240 tau positivity into clinical trials.