A Phase IIa Clinical Study to Evaluate the Efficacy and Safety of Rocbrutinib (LP-168), an Oral BTK Inhibitor, in Patients With Relapsing-Remitting Multiple Sclerosis (RRMS)
This is a randomized, controlled, multicenter, open-label Phase IIa clinical study to evaluate the efficacy and safety of rocbrutinib (LP-168), an oral BTK inhibitor, in subjects with paramagnetic rim lesion (PRL)-positive relapsing-remitting multiple sclerosis (RRMS). Approximately 30 subjects with RRMS will be enrolled and randomized 2:1 to receive rocbrutinib 25 mg once daily (experimental arm) or dimethyl fumarate (DMF) delayed-release capsules 120 mg twice daily, escalated to 240 mg twice daily after 7 days (active control arm). The treatment period is 24 weeks; subjects in the experimental arm who remain relapse-free and are assessed by the investigator as having potential benefit may enter an open-label extension and continue rocbrutinib until Week 48 after randomization. The primary endpoint is the change from screening/baseline in the number, new number, and volume of PRL lesions detected by 7T MRI at Week 24.
• Age 18 to 65 years (inclusive), male or female.
• Diagnosis of relapsing-remitting multiple sclerosis (RRMS) according to the 2017 revised McDonald criteria.
• Disease activity, meeting at least one of the following: (a) at least 2 documented relapses within 2 years, or at least 1 relapse within 1 year prior to signing the ICF; OR (b) at least 1 T1 gadolinium-enhancing (Gd+) lesion confirmed by brain MRI within 180 days prior to signing the ICF.
• Measurable lesions: at least 4 paramagnetic rim lesions (PRL) in the CNS observed by 7T MRI within 4 weeks prior to randomization.
• Concomitant medication: subjects with RRMS may receive stable-dose dimethyl fumarate (DMF); other treatments require discontinuation and washout (see Exclusion Criterion #13).
• EDSS score ≥0 and ≤5.5 at screening and baseline assessments prior to randomization.
• Neurological status stable for at least 30 days prior to randomization.
• Adequate hepatic and renal function: AST and ALT ≤2.0 × ULN; serum total bilirubin ≤1.2 × ULN (≤3.0 × ULN if documented Gilbert's syndrome); serum creatinine ≤1.5 × ULN or creatinine clearance ≥60 mL/min (Cockcroft-Gault formula).
• All male subjects and female subjects of childbearing potential must use medically acceptable contraception throughout the treatment period and for 1 week after the last dose; female subjects of childbearing potential must have a negative serum pregnancy test within 7 days before start of treatment and must not be lactating; male subjects must not donate sperm during the study and for 1 week after the last dose.
⁃ Willing and able to provide written informed consent and to comply with the study treatment schedule and visit plan.