A Study of Rocbrutinib in PRL-Positive Relapsing-Remitting Multiple Sclerosis
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-65
SponsorGuangzhou Lupeng Pharmaceutical Company LTD.
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
Subjects with a disease duration of RRMS >10 years and an EDSS score ≤2.
Neurological or autoimmune diseases other than RRMS that, in the investigator's judgment, may affect efficacy evaluation due to clinical symptoms or concomitant medication.
Contraindications to MRI or allergy to gadolinium-based contrast agents.
Currently diagnosed with or suspected of progressive multifocal leukoencephalopathy (PML), or a history of PML.
Trial design
Design model
Parallel
Treatments tested in this trial
Rocbrutinib
DrugRocbrutinib (LP-168), a novel oral BTK inhibitor, film-coated tablet. Administered 25 mg orally once daily until completion of the treatment period (maximum 48 weeks including open-label extension).
Dimethyl Fumarate
DrugDMF delayed-release capsules 120 mg/240 mg. Starting dose 120 mg twice daily; after 7 days, increase to maintenance dose 240 mg twice daily for 24 weeks.
Treatment groups
30 Participants
are divided into 2 treatment groupsGroup A: RocbrutinibExperimental treatment 1 intervention
Group B: Dimethyl Fumarate (DMF)Active comparator 1 intervention
Trial outcomes
Primary outcomes
1
Change from Screening/Baseline in the Number, New Number of Paramagnetic Rim Lesions (PRL) Detected by 7T MRI
7T MRI imaging performed at screening/baseline and Week 24 to assess the number, newly appearing number, and volume of PRL lesions.Newly developed PRLs are defined as either (1) newly appearing lesions that demonstrate a paramagnetic rim, or (2) pre-existing lesions without a paramagnetic rim at baseline that develop a new paramagnetic rim during follow-up.
Time frame
From screening/baseline to Week 242
Change from Screening/Baseline in the Volume of Paramagnetic Rim Lesions (PRL) Detected by 7T MRI
7T MRI imaging performed at screening/baseline and Week 24 to assess the Volume
Time frame
From screening/baseline to Week 24Secondary outcomes
1
Change from Screening/Baseline in number, newly occured number of PRL lesions at Weeks 12, 36, and 48 by 7T MRI
Time frame
Weeks 12, 36, and 482
Change from Screening/Baseline in Volume of PRL lesions at Week 12, 36, and 48 by 7T MRI
Time frame
Time Frame: Weeks 12, 36, and 483
Number of total and newly developed Gd+ T1 lesions at Week 12, 24, 36 and 48 by 3T MRI
Newly developed Gd+ T1 lesions are defined as Gd+ T1 lesions that are newly identified compared with the preceding MRI assessment. Persistent enhancement of the same lesion across consecutive visits will not be counted as a newly developed lesion more than once.
Time frame
Weeks 12, 24, 36, and 484
Cumulative number of new/enlarging T2 lesions at Week 12, 24, 36 and 48 by 7T MRI
Time frame
Weeks 12, 24, 36, and 48Other outcomes
1
Change in immunoglobulin quantification (IgG, IgA, IgM)
Time frame
Weeks 12, 24, 36, and 482
Change in lymphocyte subset counts (e.g., CD3+, CD4+, CD8+, and CD19+ B cells)
Time frame
Weeks 12, 24, 36, and 48Sponsors and contacts
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Source ClinicalTrials.gov