Fucoidan in the Treatment of Active Rheumatoid Arthritis

Official title

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

Overview

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.

Interventions

• Drug Fucoidan
  Background Therapy: Continued pre-existing conventional RA treatment at stable doses Intervention: Oral fucoidan Dosage Form: Size-0 gelatin capsules containing 1000mg fucoidan powder Dosage: 2000mg (2 capsules) per dose, twice daily (BID) Duration: 12 weeks continuous treatment

Primary outcome measures

• The proportion of patients achieving the American College of Rheumatology 20% improvement criteria (ACR20) at Week 12. [Time frame: at Week 12]

Secondary outcome measures (5)

• Proportion of patients achieving Disease Activity Score in 28 joints using Erythrocyte Sedimentation Rate (DAS28-ESR) remission or low disease activity at Week 12 [Time frame: at Week 12]
• Change from baseline in Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) at Week 12 [Time frame: at Week 12]
• Percentage of patients achieving good or moderate EULAR response at Week 12 [Time frame: at Week 12]
• Proportion of subjects achieving American College of Rheumatology 50% improvement criteria (ACR50) at Week 12 [Time frame: at Week 12]
• Percentage of participants meeting the 2011 ACR/EULAR Boolean remission criteria at Week 12 [Time frame: at Week 12]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Peking University People's Hospital — Beijing

Publications

• Li ZG. A new look at rheumatology in China--opportunities and challenges. Nat Rev Rheumatol. 2015 May;11(5):313-7. doi: 10.1038/nrrheum.2014.218. Epub 2015 Jan 20. PMID 25599919
• Hu F, Jiang X, Guo C, Li Y, Chen S, Zhang W, Du Y, Wang P, Zheng X, Fang X, Li X, Song J, Xie Y, Huang F, Xue J, Bai M, Jia Y, Liu X, Ren L, Zhang X, Guo J, Pan H, Su Y, Yi H, Ye H, Zuo D, Li J, Wu H, Wang Y, Li R, Liu L, Wang XY, Li Z. Scavenger receptor-A is a biomarker and effector of rheumatoid arthritis: A large-scale multicenter study. Nat Commun. 2020 Apr 20;11(1):1911. doi: 10.1038/s41467- PMID 32312978
• Yeh CW, Shih CJ, Liu TC, Chiou YL. Effects of oligo-fucoidan on the immune response, inflammatory status and pulmonary function in patients with asthma: a randomized, double-blind, placebo-controlled trial. Sci Rep. 2022 Oct 28;12(1):18150. doi: 10.1038/s41598-022-21527-3. PMID 36307493
• Konic Ristic A, Ryan S, Attjioui M, O'Connell S, Gibney ER. Effects of an Extract of the Brown Seaweed Ascophylum nodosum on Postprandial Glycaemic Control in Healthy Subjects: A Randomized Controlled Study. Mar Drugs. 2023 May 31;21(6):337. doi: 10.3390/md21060337. PMID 37367662

Identifiers

NCT: NCT07045896 · 2024PHB505-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗