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

NCT07776743 | Recruiting Phase 2 FDA Drug

• 1 other identifier: LP-168-CN205-MS
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Relapsing-remitting Multiple Sclerosis (RRMS)

Keywords

multiple sclerosis; rocbrutinib; BTK inhibitor; paramagnetic rim lesions; dimethyl fumarate

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (14)

• 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

  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

Other Outcomes (2)

• 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

Study Arms (2)

Rocbrutinib

EXPERIMENTAL

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

Dimethyl Fumarate (DMF)

ACTIVE COMPARATOR

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

Interventions

Rocbrutinib DRUG

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).

Also known as: LP-168

Rocbrutinib

Dimethyl Fumarate DRUG

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.

Dimethyl Fumarate (DMF)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.
• 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).
• Prior organ, allogeneic stem cell or bone marrow transplantation and/or anti-rejection therapy.
• Systemic chronic, recurrent or serious infection within 90 days prior to randomization (e.g., pneumonia, sepsis).
• Uncontrolled active systemic bacterial, fungal or viral infection within 4 weeks prior to randomization.
• 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.
• Prior treatment with BTK inhibitors for malignant or autoimmune indications.
• 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).
• 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).
• History of cerebral infarction or intracranial hemorrhage (except lacunar infarction judged by the investigator as not affecting enrollment).
• History of myocardial infarction within 180 days.

Sponsors & Collaborators

• Guangzhou Lupeng Pharmaceutical Company LTD.: lead

Study Sites (1)

Beijing Tiantan Hospital, Capital Medical University

Beijing, Beijing Municipality, China

RECRUITING

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis

Interventions

Dimethyl Fumarate

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Fumarates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• De-Cai Tian, M.D., Ph.D.

  Beijing Tiantan Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dr. De-Cai Tian, M.D., Ph.D.

CONTACT

+861059978585; tiandecai@bjtth.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2026
• First Posted: August 20, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: August 20, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)