Fig. 1

Study design CONSORT diagram. Forty-three participants were assessed for eligibility and 23 participants were randomized to receive placebo or 100 or 300 mg CT1812 once daily for 24 weeks. Two participants in the 100 mg and two in the 300 mg CT1812 group discontinued intervention due to AEs, and one in the 300 mg group became unavailable when pandemic-related travel restrictions precluded their return to the USA. One participant in the placebo group discontinued after experiencing an AE. PET was performed at baseline, 12 and 24 weeks to detect SV2A and at baseline and 24 weeks to detect FDG. MRI was performed and clinical outcomes were assessed at baseline, 12 and 24 weeks. CSF was sampled for biomarker assessments at baseline and 24 weeks. The participant numbers indicated for each assessment category are for the 24-week analysis