A Study of Rocbrutinib in PRL-Positive Relapsing-Remitting Multiple Sclerosis

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.

Study Overview

• Status: Recruiting
• Conditions: Relapsing-remitting Multiple Sclerosis (RRMS)
• Intervention / Treatment: Drug: Rocbrutinib; Drug: Dimethyl Fumarate

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Dr. De-Cai Tian, M.D., Ph.D.; Phone Number: +861059978585; Email: tiandecai@bjtth.org

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China
      • Recruiting
      • Beijing Tiantan Hospital, Capital Medical University
      • Contact: De-Cai Tian, M.D., Ph.D.; Phone Number: +861059978585; Email: tiandecai@bjtth.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18 to 65 years (inclusive), male or female.
2. Diagnosis of relapsing-remitting multiple sclerosis (RRMS) according to the 2017 revised McDonald criteria.
3. 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.
4. Measurable lesions: at least 4 paramagnetic rim lesions (PRL) in the CNS observed by 7T MRI within 4 weeks prior to randomization.
5. Concomitant medication: subjects with RRMS may receive stable-dose dimethyl fumarate (DMF); other treatments require discontinuation and washout (see Exclusion Criterion #13).
6. EDSS score ≥0 and ≤5.5 at screening and baseline assessments prior to randomization.
7. Neurological status stable for at least 30 days prior to randomization.
8. 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).
9. 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.
10. Willing and able to provide written informed consent and to comply with the study treatment schedule and visit plan.

Exclusion Criteria:

1. Subjects with a disease duration of RRMS >10 years and an EDSS score ≤2.
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.
3. Contraindications to MRI or allergy to gadolinium-based contrast agents.
4. Currently diagnosed with or suspected of progressive multifocal leukoencephalopathy (PML), or a history of PML.
5. History of malignancy within 2 years prior to randomization, except adequately treated basal cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the breast, localized squamous cell carcinoma, and malignancies confirmed by the investigator to have been cured by surgery or other treatments.
6. History of serious infection or potential risk of serious infection, including: HIV infection; syphilis or tuberculosis infection (except previously infected subjects judged cured by the investigator or specialist); HBsAg- or HBcAb-positive with HBV-DNA above the upper limit of normal of the study site (subjects with HBsAg- or HBcAb-positive but HBV-DNA negative may be enrolled and require anti-HBV therapy during the study); HCV antibody-positive with HCV-RNA above the ULN or qualitatively positive (HCV-RNA-negative subjects may be enrolled).
7. Prior organ, allogeneic stem cell or bone marrow transplantation and/or anti-rejection therapy.
8. Systemic chronic, recurrent or serious infection within 90 days prior to randomization (e.g., pneumonia, sepsis).
9. Uncontrolled active systemic bacterial, fungal or viral infection within 4 weeks prior to randomization.
10. Receipt of live attenuated vaccines within 4 weeks prior to randomization, or planned during the study or within 4 weeks after the end of study treatment.
11. Prior treatment with BTK inhibitors for malignant or autoimmune indications.
12. Any other medical condition or complication that adversely affects participation in the study, including but not limited to: short expected survival due to pre-existing health conditions; inability to undergo primary efficacy endpoint evaluation; severe and/or uncontrolled systemic diseases judged unsuitable for the study by the investigator (including uncontrolled hypertension or diabetes ≥CTCAE Grade 2, unstable angina, congestive heart failure, respiratory diseases requiring continuous oxygen, severe thromboembolism, uncontrolled major bleeding or bleeding from vital organs, known platelet dysfunction, severe hepatic/renal or metabolic diseases such as cirrhosis or renal failure).
13. Poor cardiac function: NYHA class ≥2, or LVEF <50% by echocardiography, or significant abnormalities on screening ECG (atrial fibrillation/flutter, second-degree type II or third-degree atrioventricular block, CTCAE ≥Grade 2 bradycardia, or mean QTcF ≥450 ms on ≥3 independent ECGs).
14. History of cerebral infarction or intracranial hemorrhage (except lacunar infarction judged by the investigator as not affecting enrollment).
15. History of myocardial infarction within 180 days.
16. Receipt of any investigational drug within 3 months or 5 half-lives (whichever is longer) prior to randomization.
17. Receipt of the following MS treatments within the specified periods prior to randomization: systemic corticosteroids within 4 weeks; intravenous immunoglobulin or S1P receptor modulators (e.g., fingolimod) within 2 months; azathioprine, mycophenolate mofetil or methotrexate within 3 months; anti-CD20 monoclonal antibodies (e.g., ofatumumab, ocrelizumab, rituximab) within 6 months, or if the last dose was >6 months before screening but peripheral blood B cells have not recovered to normal levels; teriflunomide within 6 months (washout may be shortened to 1 month if plasma teriflunomide concentration <0.02 mg/L after rapid clearance); anti-α4-integrin antibody (natalizumab) within 6 months; anti-CD52 antibody (alemtuzumab) within 4 years; prior total lymphoid irradiation, mitoxantrone (with cardiotoxicity or cumulative dose ≥120 mg/m²), or other potent immunosuppressive therapy with long-lasting effects.
18. Major surgery (usually defined as Grade III or above per institutional regulations) or serious trauma within 4 weeks prior to randomization.
19. Planned long-term use during the study of: strong or moderate CYP3A inhibitors or inducers, OATP1B3 sensitive substrates, or proton pump inhibitors (see Appendices 2 and 3).
20. Receipt of anticoagulants or antiplatelet agents within 7 days or 5 half-lives (whichever is longer) prior to randomization.
21. Conditions affecting the ability to swallow the drug, or conditions seriously affecting drug absorption or pharmacokinetics (e.g., refractory nausea/vomiting, short bowel syndrome).
22. Disease symptoms unfavorable for oral administration of the study drug; unresolved toxicity from prior treatment affecting AE assessment; underlying disease leading to poor compliance; or alcohol/drug abuse or dependence.
23. Hypersensitivity to rocbrutinib tablets/dimethyl fumarate capsules or any of their excipients.
24. Any other condition judged by the investigator as unsuitable for participation in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rocbrutinib; Rocbrutinib tablet orally once daily, taken on an empty stomach (except 1 h before to 2 h after meals) with approximately 240 mL of water; tablets must be swallowed whole. Continue until the end of the treatment period; subjects without relapse and with potential benefit may enter the open-label extension through Week 48.	Drug: Rocbrutinib; Rocbrutinib (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).; Other Names: LP-168
Active Comparator: Dimethyl Fumarate (DMF); DMF 120 mg orally twice daily as starting dose; after 7 days, escalate to maintenance dose 240 mg twice daily for 24 weeks. May be taken with food to reduce flushing.	Drug: Dimethyl Fumarate; DMF 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From screening/baseline to Week 24
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	From screening/baseline to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Screening/Baseline in number, newly occured number of PRL lesions at Weeks 12, 36, and 48 by 7T MRI		Weeks 12, 36, and 48
Change from Screening/Baseline in Volume of PRL lesions at Week 12, 36, and 48 by 7T MRI		Time Frame: Weeks 12, 36, and 48
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.	Weeks 12, 24, 36, and 48
Cumulative number of new/enlarging T2 lesions at Week 12, 24, 36 and 48 by 7T MRI		Weeks 12, 24, 36, and 48
Change from Screening/Baseline in brain volume at Week 12, 24 ,36 and 48 by 7T MRI		Weeks 12, 24, 36, and 48
Change in Expanded Disability Status Scale (EDSS) score	The Expanded Disability Status Scale (EDSS) is scored from 0 (normal neurological examination) to 10 (death); higher scores indicate greater disability	Weeks 12, 24, 36, and 48
Adjusted cumulative annualized relapse rate (ARR)		From randomization up to Week 48
Change in Timed 25-Foot Walk (T25FW) results	The Timed 25-Foot Walk (T25FW) is a quantitative ambulation test: the time (in seconds) for the subject to walk 25 feet (7.62 meters) as fast as possible, assessing lower limb motor function; an increase from baseline indicates functional worsening	Weeks 12, 24, 36, and 48
Change in 9-Hole Peg Test (9HPT) results	The 9-Hole Peg Test (9HPT) is a quantitative upper extremity function test: the time (in seconds) for the subject to place 9 pegs into a pegboard and remove them, tested for both dominant and non-dominant hands, assessing fine motor function; an increase from baseline indicates functional worsening	Weeks 12, 24, 36, and 48
Time to first confirmed disability progression (CDP) event	CDP is defined as a clinically significant increase in EDSS score from baseline confirmed over at least 4 weeks (increase ≥1.5 points from a baseline of 0; ≥1.0 point from a baseline of 0.5 to ≤5.5; ≥0.5 point from a baseline >5.5)	From date of randomization until the date of first confirmed disability progression, assessed up to Week 48
Number of participants with treatment-emergent adverse events (TEAEs) as assessed by CTCAE v5.0		From first dose of study treatment through 4 weeks after the end of the 24-week treatment period (or through 4 weeks after the end of the 48-week treatment period including the open-label extension), including the safety follow-up period
Number of participants with treatment-related adverse events (TRAEs) as assessed by CTCAE v5.0		From first dose of study treatment through 4 weeks after the end of the 24-week treatment period (or through 4 weeks after the end of the 48-week treatment period including the open-label extension), including the safety follow-up period
Number of participants with serious adverse events (SAEs) as assessed by CTCAE v5.0		From first dose of study treatment through 4 weeks after the end of the 24-week treatment period (or through 4 weeks after the end of the 48-week treatment period including the open-label extension), including the safety follow-up period
Number of participants with clinically significant abnormal findings on physical examination		From first dose of study treatment through 4 weeks after the end of the 24-week treatment period (or through 4 weeks after the end of the 48-week treatment period including the open-label extension), including the safety follow-up period

Other Outcome Measures

Outcome Measure	Time Frame
Change in immunoglobulin quantification (IgG, IgA, IgM)	Weeks 12, 24, 36, and 48
Change in lymphocyte subset counts (e.g., CD3+, CD4+, CD8+, and CD19+ B cells)	Weeks 12, 24, 36, and 48

Collaborators and Investigators

• Sponsor: Guangzhou Lupeng Pharmaceutical Company LTD.
• Investigators: Principal Investigator: De-Cai Tian, M.D., Ph.D., Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: August 7, 2026
• First Submitted That Met QC Criteria: August 17, 2026
• First Posted (Actual): August 20, 2026

Study Record Updates

• Last Update Posted (Actual): August 20, 2026
• Last Update Submitted That Met QC Criteria: August 17, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: multiple sclerosis; BTK inhibitor; dimethyl fumarate; rocbrutinib; paramagnetic rim lesions
• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Organic Chemicals; Acids, Acyclic; Carboxylic Acids; Fumarates; Dicarboxylic Acids; Dimethyl Fumarate
• Other Study ID Numbers: LP-168-CN205-MS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No