FRI0159 Results of a Single Dose Ascending First-in-Man Trial of a Novel Biologic, Human Stress Protein Rasolvir (BIP) in Rheumatoid Arthritis (RA): The Ragulo Trial

Background Rasolvir (BiP) is a human endoplasmic reticulum-resident stress protein. In pre-preclinical studies it has prolonged anti-inflammatory properties by the induction of regulatory cells. A single intravenous infusion suppresses ongoing collagen-induced arthritis in the mouse; ameliorates arthritis and inhibits bone damage in the TNFa-trangenic mouse; and suppresses inflammation in the RA synovial membrane/SCID transplantation model (see review). It is thus a potential new therapy for RA acting by a novel mode of action. Objectives The objectives of this randomised placebo-controlled, dose ascending double blind Phase I/IIA trial of Rasolvir were safety (Primary Objective) and efficacy as measured by the DAS28 (Secondary Objective). Methods Forty-one patients with established active RA, who had failed DMARDs, were assessed; 24 fulfilled the inclusion/exclusion criteria. They were sequentially assigned to three cohorts each of 8 patients randomly allocated to receive placebo (2 patients) or Rasolvir (6 patients). Patients received a single intravenous infusion over 1hr and observed as inpatients overnight. Cohort 1 received 1mg rasolvir; 2 5mg; and 3 15mg. No patients were re-treated. Clinical, rheumatological and laboratory assessments for safety and efficacy (DAS28) were carried out at stated intervals for 12 weeks. Results SAFETY. No infusion reactions or serious adverse reactions were noted. Adverse events were evenly distributed between placebo and IMP groups demonstrating no Rasolvir-related toxicity. Haematological, renal and metabolic parameters remained within the normal range. EFFICACY. Six patients receiving placebo and 6 in each Rasolvir group were available for analysis. Although the placebo group had a high frequency of moderate EULAR responses, the highest rate of EULAR good responses was observed in the Rasolvir groups. Good EULAR responses were seen as early as 3 weeks after the infusion. At 12 weeks, 3 patients who had received Rasolvir were still in remission (DAS28 ≤2.6). Conclusions Rasolvir is safe when administered up to a dose of 15mg in patients with active RA. A higher rate of good EULAR response after a single dose of Rasolvir suggests that it merits further study as a treatment447855328407 of RA. References Shields AM, Panayi GS, Corrigall, V. A new-age for biologic therapies: long-term drug-free therapy with BiP. Front Immunol 2012;17:3-17. Acknowledgements Study funded by Arthritis Research UK. Support received from the Biomedical Research Centre KCL; Quintiles for the infusion and overnight stay; Kings Health Partners Joint Clinicat Trials Office; the Pharmacy at GSTT. The Rasolvir produced at CBC, Bristol University. Disclosure of Interest B. Kirkham Grant/research support from: AbbVie;UC, Consultant for: Novartis; AbbVie; BMS; Lilly; MSD, Speakers bureau: BMS; MSD; UCB, K. Chaabo: None declared, C. Hall: None declared, A. Vincent: None declared, J. Vasconcelos: None declared, T. Prevost: None declared, G. Panayi Shareholder of: Immune Regulation Ltd, V. Corrigall Shareholder of: Immune Regulation Ltd