To report MRI outcomes at Week (W) 96 (2 years) in LTS16004 (NCT03996291), an ongoing long-term safety (LTS) extension study of the Phase 2b trial (NCT03889639) of tolebrutinib, a brain-penetrant Bruton’s tyrosine kinase inhibitor in participants with relapsing multiple sclerosis.
In the double-blind phase (DBP) of the Phase 2b trial, tolebrutinib was well-tolerated over 12 weeks with dose-dependent reductions in new gadolinium-enhancing T1 and new/enlarging T2-lesions.
In LTS Part A, participants continued receiving their DBP tolebrutinib dose (5, 15, 30, or 60mg/day) until Phase 3 dose selection. In open-label Part B, all participants received 60mg/day. MRI outcomes included numbers of new gadolinium-enhancing T1 and new/enlarging T2-lesions, T2-lesion volume change, slowly evolving lesions (SEL), and paramagnetic rim lesions (PRL).
124/125 participants completed Part A and transitioned to Part B; 114 (90.5%) remained on study as of 18 February 2022 (W96 cut-off). Mean age±SD at DBP baseline was 37.7±9.6 years (range 19–56); 69% were women. New gadolinium-enhancing lesion counts remained low in 60/60-mg arm through W96 and were reduced in other arms W48 through W96 (W96 mean±SD: 0.85±2.5, 0.41±0.91, 0.90±2.16, 0.31±0.66 in 5/60-, 15/60-, 30/60-, 60/60-mg arms, respectively). New/enlarging T2-lesion counts remained low for 60/60-mg. T2-lesion volume change remained low for 60/60-mg (W96 vs baseline [mean±SD]: +0.38±2.11 cm3). Median (IQR) W96 SEL volume was 247.5 (84–420), 258 (66–906), 570 (133.5–1011), and 244.5 (87–939) mm3 for 5/60-, 15/60-, 30/60-, and 60/60-mg, respectively. PRL count remained unchanged in 18 participants; 2 had 1 PRL at baseline but none at W96, and 3 had 1–3 additional PRL at W96 vs baseline (none in the 60/60-mg arm).