Safety, Tolerability, and Pharmacodynamic Exploration of Orelabrutinib in Patients With Amyotrophic Lateral Sclerosis (ALS)

This is a single-center, open-label, dose-escalation, investigator-initiated pilot study to evaluate the safety, tolerability, dose-limiting toxicity (DLT), and pharmacodynamic signals of orelabrutinib in patients with amyotrophic lateral sclerosis (ALS). A 12-week run-in observation period will be used to establish each participant's historical ALSFRS-R decline slope. Participants will receive orelabrutinib 50 mg once daily (QD), 100 mg QD, or optional 150 mg QD using a 3+3 dose-escalation design for 24 weeks, followed by a 4-week safety follow-up.