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
Authors: B. Kirkham, K. Chaabo, C. Hall, A. Vincent, J. Vasconcelos, T. Prevost, G. Panayi, V. Corrigall
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> 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. <h3>Objectives</h3> 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). <h3>Methods</h3> 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 <i>a single intravenous infusion over 1hr</i> 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. <h3>Results</h3> 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 <i>moderate</i> EULAR responses, the highest rate of EULAR <i>good</i> 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). <h3>Conclusions</h3> 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. <h3>References</h3> 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. <h3>Acknowledgements</h3> 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. <h3>Disclosure of Interest</h3> 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