International multicenter randomized, placebo-controlled phase III clinical trial of β-d-mannuronic acid in rheumatoid arthritis patients

• Published in: Inflammopharmacology 2019-10, Vol.27 (5), p.911-921
• Main Authors: Rezaieyazdi, Zahra, Farooqi, Abid, Soleymani-Salehabadi, Hossein, Ahmadzadeh, Arman, Aslani, Mona, Omidian, Saiedeh, Sadoughi, Arezoo, Vahidi, Zohreh, Khodashahi, Mandana, Zamurrad, Shazia, Mortazavi-Jahromi, Seyed Shahabeddin, Fallahzadeh, Hossein, Hosseini, Mostafa, Aghazadeh, Zahra, Ekhtiari, Parvin, Matsuo, Hidenori, Rehm, Bernd H. A., Cuzzocrea, Salvatore, D’Aniello, Antimo, Mirshafiey, Abbas
• Format: Article
• Language: English
• Subjects: Allergology; Antibodies, Monoclonal - therapeutic use; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - drug therapy; Biomedical and Life Sciences; Biomedicine; Dermatology; Double-Blind Method; Female; Gastroenterology; Hexuronic Acids - therapeutic use; Humans; Immunology; Male; Middle Aged; Original Article; Pharmacology/Toxicology; Rheumatology; Severity of Illness Index; Treatment Outcome
• ISSN: 0925-4692; 1568-5608
• DOI: 10.1007/s10787-018-00557-2

Background The oral administration of drug β- d -mannuronic acid (M2000) showed a potent therapeutic effect in phase I/II study in rheumatoid arthritis (RA) patients. Here, our aim is to assess the efficacy and safety of this new drug in RA patients under a multinational, randomized placebo-controlled phase III clinical trial. Method Patients ( n  = 288) with active disease at baseline and inadequate response to conventional drugs were randomly allocated to three groups; (1) receiving mannuronic acid at a dose of two capsules (500 mg) per day orally for 12 weeks, (2) placebo-controlled, and (3) conventional. The primary endpoints were the America College of Rheumatology 20 response (ACR20), 28-joint disease activity score (DAS28) and Modified Health Assessment Questionnaire-Disability Index (M-HAQ-DI). In addition, the participants were followed-up for safety assessment. Results In this phase III trial, after 12 weeks of treatment, there was a significant reduction in ACR20 between mannuronic-treated patients compared to placebo and conventional groups. Moreover, there was a similar significant improvement for DAS28 following mannuronic therapy. The statistical analysis showed a significant reduction in the swollen and tender joint count in mannuronic-treated patients compared with the placebo group. On the other side, mannuronic acid showed no-to-very low adverse events in comparison to placebo. Conclusion The results of this multinational, phase III clinical trial provided a potent evidence base for the use of β- d -mannuronic acid as a new highly safe and efficient drug in the treatment of RA.