Can Cxcl8 Inhibitor (reparixin) Improve Islet Engraftment And Clinical Outcomes After Islet Allotransplantation? University Of Chicago Preliminary Results From A Phase 3 Multicenter Randomized, Double-blinded, Prospective Study.
1University of Chicago Medicine, Chicago, IL, 2Medical University of Gdansk, Gdansk, Poland
Meeting: 2019 American Transplant Congress
Abstract number: D293
Keywords: Engraftment, Islets
Session Information
Session Name: Poster Session D: Pancreas and Islet: All Topics
Session Type: Poster Session
Date: Tuesday, June 4, 2019
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: Reparixin is a novel CxCR1/2 chemokine receptor-blocking molecule, which has been shown improving islet engraftment in animal models. A multicenter trial was organized to test Reparixin, and now we present preliminary results from our center only, before outcomes from the trial are available.
*Methods: 12 patients with brittle T1DM were randomized blindly (2:1) to Reparixin or placebo group. All patients received the same immunosuppression (anti thymocyte globulin, tacrolimus, mycophenolate mofetil) and islet allotransplantation with up to 2 islet infusions. Reparixin or placebo was administrated as a 7-day continuous infusion after the transplant in respective groups.
*Results: Reparixin group consisted of 8 patients (4F/4M), whereas control of 4 (3F/1M). Patient characteristics did not differed significantly: age 46 (28-56) vs 40 (30-48), weight 77kg (42-93) vs 74 (58-82), BMI 26 (19-29.9) vs 25 (21-29.9), A1c 7.4 (6.8-8.1) vs 7.1 (6.8-8.6), daily insulin requirements 34u (19-68) vs 37 (29-60), islet dose 657kIEQ (372-1,230) vs 952 (777-1,302) for Reparixin vs placebo group, respectively. Islet quality did not differ between groups- GSIR was 1.75 (0.78-10.75) vs 1.43(0.46-5), and viability 93% vs 94%, respectively. Clinical outcomes were better (although not statistically significant) in Reparixin than in placebo group: 4 (50%) vs none (0%) patients became insulin independent after only one islet infusion and maintained an optimal glucose control (A1c<6) without insulin supplementation over 2 years (2.2, >4.5,>5,>5 years), respectively (p=0.2). Islet Engraftment Index (IEI) measured on day 75 based on the ratio of area under the curve for serum c-peptide (AUC c-peptide) and glucose (AUC glucose) in 120 min mixed meal test standardized for islet mass in IEQ during the first transplant was higher in each of 5 out of 8 individuals without early complications in Reparixin group: 5.92, 6.02, 7.04, 9.44, 11.99 [(ng/ml)/(mg/dl)/IEQ]*104 than in any patient without early complications in the placebo group (0, 4.56, 5.02) (p=0.035). Islet function measured based on BETA-2 was higher but did not reached statistical difference (p=0.07); BETA-2 was 15.5, 21, 22, 23, 23 in patients receiving Reparixin vs 0, 10, 19 in placebo group. Remaining 3 individuals from Reparixin group and one from placebo group had IEI compromised by the early complications: severe cytokine release syndrome- IEI=0 and antibody mediated rejection in two patients- IEI= 0 and 0.67, and similarly antibody mediated rejection in one patientin placebo group- IEI=2.61.
*Conclusions: Half of the patients from Reparixin group achieved long- term (>2 years) insulin independence after only one islet infusion, while none from placebo group had such outcome. Islet engraftment index was significantly higher in Reparixin group than in placebo, while assessed in patients without complications. Further studies are warranted to confirm our preliminary results.
To cite this abstract in AMA style:
Bachul P, Golab K, Basto L, Wang L, Tibudan M, Golebiewska J, Para M, Perea L, Antic F, Fung J, Witkowski P. Can Cxcl8 Inhibitor (reparixin) Improve Islet Engraftment And Clinical Outcomes After Islet Allotransplantation? University Of Chicago Preliminary Results From A Phase 3 Multicenter Randomized, Double-blinded, Prospective Study. [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/can-cxcl8-inhibitor-reparixin-improve-islet-engraftment-and-clinical-outcomes-after-islet-allotransplantation-university-of-chicago-preliminary-results-from-a-phase-3-multicenter-randomized-double/. Accessed November 24, 2024.« Back to 2019 American Transplant Congress