Safety, tolerability, and pharmacokinetics of single and multiple ascending doses of THN391, a monoclonal antibody targeting the fibrin inflammatory epitope: Phase 1a clinical trial results

THN391 was safe and well-tolerated at all doses with only 6 adverse events which were mild, related to the infusion site and resolved without sequelae. There were no clinically significant changes observed in lab results, vital signs, or ECG. THN391 had no impact on coagulation and fibrinolysis, as measured by PT, aPTT and ROTEM. Interim population PK modeling suggests that THN391 exhibits dose proportional pharmacokinetics and a terminal half-life of 38 days, supporting monthly or less frequent dosing CONCLUSION: THN391, a first-in-class antibody targeting fibrin-induced inflammation, was found to be safe and well-tolerated in a Phase 1a study, with a half-life supporting monthly IV dosing. A Phase 1b study is planned in patients with early AD and confirmed cerebral small vessel disease (cSVD). ApoE4 homozygotes will be included. The study will assess safety, PK, early signals of efficacy based on CSF and plasma biomarkers of inflammation and disease progression, brain MRI (ASL and DCE-MRI) and cognition.