Fucoidan in the Treatment of Active Rheumatoid Arthritis

Fucoidan Therapy in Adults With Active Rheumatoid Arthritis and Inadequate Response to Conventional DMARDs: a Multicenter, Single-arm, Open-label, Phase 2 Trial

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint destruction and autoantibody production. Scavenger receptor-A (SR-A), a pattern recognition receptor primarily expressed on myeloid-derived cells, is significantly elevated in the serum of RA patients. Genetic knockout of SR-A completely protects mice from collagen-induced arthritis (CIA). As an SR-A inhibitor, fucoidan markedly suppresses the progression of CIA in mice. Given the potential role of SR-A in RA pathogenesis, the investigators hypothesize that fucoidan may exert therapeutic effects in RA by specifically targeting human SR-A.

This study aims to investigate the efficacy of fucoidan in RA treatment through a multicenter, single-arm, open-label trial, providing original insights into its clinical application. The investigators plan to enroll 40 patients with a 12-week follow-up period. Clinical manifestations, laboratory parameters, and disease activity will be systematically evaluated to assess therapeutic outcomes. The findings will provide evidence-based medical data for RA treatment strategies.

Inclusion Criteria:

• Patients aged 18-65 years (inclusive) at screening, regardless of gender, with a minimum weight of 35 kg.
• Patients meeting the 2010 ACR classification criteria for rheumatoid arthritis.
• Patients with active rheumatoid arthritis showing moderate-to-high disease activity (DAS28-ESR >3.2) despite current treatment.
• If receiving conventional NSAIDs or other pain medications, the dose must have been stable for at least 2 weeks prior to the first study drug administration and remain unchanged during the study period.
• If taking oral corticosteroids, patients must have been on treatment for at least 4 weeks, with the dose stabilized at an average of ≤1.0 mg/kg/day prednisone equivalent for at least 4 weeks prior to the first study drug administration, and remain unchanged during the study period.
• If receiving DMARDs (methotrexate ≤25 mg/week with folic acid supplementation [recommended ≥5 mg/week] or leflunomide ≤40 mg/day), patients must have been on treatment for ≥8 weeks, with the dose stable for at least 4 weeks prior to the first study drug administration, and remain unchanged during the study period.
• Female patients of childbearing potential must have negative serum and urine pregnancy test results at screening.
• From the time of signing the informed consent form throughout the study and for 3 months after the last dose, female patients of childbearing potential and male patients who have not undergone vasectomy must use effective contraception.
• Patients must be willing and able to comply with the study restrictions.
• Patients must sign the informed consent form, understand the purpose and procedures of the study, and be willing to participate in the study.

Exclusion Criteria:

• Patients currently receiving biologic therapy.
• Patients with other inflammatory joint diseases or connective tissue diseases.
• Patients with significant bone marrow impairment or significant anemia, leukopenia, or thrombocytopenia secondary to inactive rheumatoid arthritis.
• Patients with persistent or severe infections within 3 months prior to enrollment.
• Patients with uncontrolled hypertension, uncontrolled diabetes, unstable ischemic heart disease, active inflammatory bowel disease, active peptic ulcers, terminal illnesses, or other conditions that, in the investigator's opinion, would pose a risk to the patient's participation in the study.
• Patients with clinically relevant cardiovascular, hepatic, neurological, endocrine, or other major systemic diseases that would complicate the implementation of the protocol or interpretation of study results.
• Patients with severe hypoalbuminemia (serum albumin <30 g/L), such as due to severe liver disease or nephrotic syndrome.
• Patients with moderate or severe renal impairment, defined as serum creatinine >133 μmol/L (or 1.5 mg/dL).
• Patients with a recent or clinically significant history of drug or alcohol abuse.
• Patients with impaired liver function or persistent alanine aminotransferase levels >2 times the upper limit of normal.
• Pregnant patients.
• Breastfeeding patients.
• Patients with congenital or acquired severe immunodeficiency, a history of cancer or lymphoproliferative disorders, or those who have undergone total lymphoid irradiation.
• Patients with known HIV-positive status.
• Patients with known positive serology for hepatitis B or hepatitis C.
• Patients enrolled in any other clinical trial involving off-label use of investigational drugs or devices, or enrolled in any other type of medical research.
• Patients with any active infection (including chronic or localized infections) requiring antimicrobial therapy within 28 days prior to the first study drug dose.
• Patients with a body mass index (BMI) <18.5 kg/m² or >30 kg/m².