Rdp58 Is a Novel and Potentially Effective Oral Therapy for Ulcerative Colitis
Open Access
- 1 August 2005
- journal article
- clinical trial
- Published by Oxford University Press (OUP) in Inflammatory Bowel Diseases
- Vol. 11 (8), 713-719
- https://doi.org/10.1097/01.mib.0000172807.26748.16
Abstract
RDP58 is a novel anti-inflammatory d-amino acid decapeptide that inhibits synthesis of proinflammatory cytokines by disrupting cell signaling at the pre-MAPK MyD88-IRAK-TRAF6 protein complex. We therefore evaluated its efficacy and safety in parallel multicenter, double-blind, randomized concept studies in ulcerative colitis (UC). In the first trial, 34 patients with mild to moderate active UC were randomized (1:2) to placebo (n = 13) or RDP58 100 mg (n = 21). In the second trial, 93 similar patients were randomized (1:1:1) to placebo (n = 30) RDP58 200 mg (n = 31), or RDP 300 mg (n = 32). In both studies, treatment success was defined as a simple clinical colitis activity index score of no more than 3 at 28 days. Sigmoidoscopy and rectal biopsy (at baseline and 28 days) and safety measures (baseline and 28 and 56 days) were other endpoints. Treatment success on RDP 100 mg was 29% versus 46% on placebo (P = 0.46). There were no significant differences in sigmoidoscopy or histology score. In the second study, treatment success on the higher doses of RDP58 (200 and 300 mg) was 71% and 72%, respectively, versus 43% on placebo (P = 0.016). Improvements in sigmoidoscopy scores (41% on 200 mg and 46% on 300 mg versus 32% on placebo) did not reach significance, but histology scores improved significantly (P = 0.002) versus placebo. Overall, adverse events were no different between placebo (3.3 ± 2.4) and RDP58 (2.7 ± 1.4, 300-mg group). RDP58 at a dose of 200 or 300 mg, but not 100 mg, was effective in mild-to-moderate UC. RDP58 was safe and well tolerated, and its novel action makes it an attractive potential therapy.Keywords
This publication has 21 references indexed in Scilit:
- RDP58, a novel immunomodulatory peptide, ameliorates clinical signs of disease in the Lewis rat model of acute experimental autoimmune encephalomyelitisJournal of Neuroimmunology, 2004
- RDP58, a novel anti-inflammatory peptide, inhibits multiple intracellular messenger pathways and transcription factors to block TNF-α, IFN-γ, and IL12 productionGastroenterology, 2003
- RDP58, a Novel Immunomodulatory Peptide with Anti-Inflammatory Effects. A Pharmacological Study in Trinitrobenzene Sulphonic Acid Colitis and Crohn DiseaseScandinavian Journal of Gastroenterology, 2003
- Rational Design and Development of RDP58Current Pharmaceutical Design, 2002
- RDP58, a locally active TNF inhibitor, is effective in the dextran sulphate mouse model of chronic colitisInflammation Research, 2002
- Orally administered RDP58 reduces the severity of dextran sodium sulphate induced colitisAnnals Of The Rheumatic Diseases, 2002
- Image of the monthGastroenterology, 2002
- IL-1-induced NFκB and c-Jun N-terminal kinase (JNK) activation diverge at IL-1 receptor-associated kinase (IRAK)Proceedings of the National Academy of Sciences of the United States of America, 2001
- Inhibition of Tumor Necrosis Factor mRNA Translation by a Rationally Designed Immunomodulatory PeptideJournal of Biological Chemistry, 2000
- MyD88: An Adapter That Recruits IRAK to the IL-1 Receptor ComplexImmunity, 1997