OBJECTIVE: Reparixin is an inhibitor of CXCR1/2 chemokine receptor shown to be an effective anti-inflammatory adjuvant in a pilot clinical trial in allotransplant recipients. RESEARCH DESIGN AND METHODS: A phase 3, multicenter, randomized, double-blind, parallel-assignment study (NCT01817959) was conducted in recipients of islet allotransplants randomized (2:1) to reparixin or placebo in addition to immunosuppression. Primary outcome was the area under the curve (AUC) for C-peptide during the mixed-meal tolerance test at day 75 ± 5 after the first and day 365 ± 14 after the last transplant. Secondary end points included insulin independence and standard measures of glycemic control. RESULTS: The intention-to-treat analysis did not show a significant difference in C-peptide AUC at both day 75 (27 on reparixin vs. 18 on placebo, P = 0.99) and day 365 (24 on reparixin vs. 15 on placebo, P = 0.71). There was no statistically significant difference between treatment groups at any time point for any secondary variable. Analysis of patient subsets showed a trend for a higher percentage of subjects retaining insulin independence for 1 year after a single islet infusion in patients receiving reparixin as compared with patients receiving placebo (26.7% vs. 0%, P = 0.09) when antithymocyte globulin was used as induction immunosuppression. CONCLUSIONS: In this first double-blind randomized trial, islet transplantation data obtained with reparixin do not support a role of CXCR1/2 inhibition in preventing islet inflammation-mediated damage.

Department of Clinical Science Intervention and Technology Karolinska Institutet Karolinska Sweden

Institute for Clinical and Experimental Medicine Prague Czech Republic

Institute of Cellular Medicine Newcastle University and Freeman Hospital Newcastle upon Tyne Hospitals NHS Foundation Trust Newcastle upon Tyne U K

Ospedale Niguarda Ca' Granda Milan Italy

Research and Development Department Dompé farmaceutici S p A Milan Italy

San Raffaele Diabetes Research Institute IRCCS Ospedale San Raffaele Milan Italy

Skåne University Hospital Malmö Sweden

Transplantation Institute University of Chicago Medicine Chicago IL

University of Gothenburg Göteborg Sweden

Uppsala University Uppsala Sweden

Diabetes Care. 2020 Apr;43(4):698-700. doi: 10.2337/dci19-0080. PubMed

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ClinicalTrials.gov
NCT01817959