Study to Assess Efficacy & Safety of Reparixin in Pancreatic Islet Transplantation
Condition: Islet Transplantation in Diabetes Mellitus Type 1
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 3

Summary: 
      The objective of this clinical trial was:

      - to assess whether Reparixin leads to improved transplant outcome as measured by glycaemic
      control following intra-hepatic infusion of pancreatic islets in patients with Type 1
      diabetes (T1D). The safety of Reparixin in the specific clinical setting was also evaluated.

      Background: The chemokine CXCL8 plays a key role in the recruitment and activation of
      polymorphonuclear neutrophils in post-ischemia reperfusion injury after organ
      transplantation. Reparixin is the first low molecular weight blocker of CXCL8 biological
      activity in clinical development. Thus, the use of reparixin may emerge as a potential key
      component in the sequentially integrated approach to immunomodulation and control of non
      specific inflammatory events surrounding the early phases of pancreatic islet transplantation
      in T1D patients.
    

Detailed description: 
      Pancreatic islet transplantation has become a feasible option in the treatment of T1D which
      offers advantages over whole pancreas transplantation.

      Several strategies are being evaluated, including anti-TNFα, aimed to prevent early
      inflammatory events that limit islet engraftment. Among possible mechanisms CXCL8 could play
      a crucial role in triggering the inflammatory reaction and might represent a relevant
      therapeutic target to prevent early graft failure.

      Preliminary data obtained in transplanted patients recruited in the ongoing pilot trial
      coupled with the safety shown in human phase 1 and 2 studies provide a sound rationale for
      further development of reparixin in islet transplantation and prompted the conduct of this
      phase 3 clinical, multicentre, randomised, double-blind, parallel assignment study aimed at
      assessing the efficacy and safety of reparixin in preventing graft dysfunction after islet
      transplantation in T1D subjects.

      At least 42 patients receiving pancreatic islet transplant were involved. Patients might
      receive up to 2 islet transplants, with the second transplant on average 6 months after the
      first one. Patients were randomly (2:1) assigned to receive either reparixin or placebo
      (control group). The Investigational Product was administered as an added on treatment to the
      immunosuppressant regimen.
    

Intervention name(s): Reparixin; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Continuous i.v. infusion into a central vein for 7 days, starting approximately 12 hrs (6-18 hrs) before each pancreatic islet infusion.The Investigational Product (IP) were to be administered as an add-on treatment for the immunosuppressant regimen.; Continuous infusion at a volume/rate matching active treatment.The placebo was to be administered as well as an add-on treatment for the immunosuppressant regimen.
Other intervention name(s): REP
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Pancreatic islet transplantation; Diabetes Mellitus Type 1; Islet transplantation graft survival & function