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
Intervention: Reparixin; Placebo
Intervention description: 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.
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 51.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Pancreatic islet transplantation; Diabetes Mellitus Type 1; Islet transplantation graft survival & function

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Ages 18-70 years, inclusive.

          -  Patients eligible for a pancreatic islet transplantation program

          -  Planned intrahepatic islet transplantation alone from a non-living donor with brain
             death.

          -  Patients willing and able to comply with the protocol procedures for the duration of
             the study, including scheduled follow-up visits and examinations.

          -  Patients who have given written informed consent, prior to any study-related procedure
             not part of normal medical care, with the understanding that consent may be withdrawn
             by the patient at any time without prejudice to their future medical care.

        Exclusion Criteria:

          -  Recipients of any previous transplant, including recipients of previous pancreatic
             islet transplantation.

          -  Recipients of islet from a non-heart beating donor.

          -  Pre-transplant average daily insulin requirement >1 IU/kg/day.

          -  Pre-transplant (the more recent value obtained within the 4 months prior to enrolment)
             HbA1c >11%.

          -  Patients with inadequate renal reserve as per calculated creatinine clearance (CLcr) <
             60 mL/min according to the Cockcroft-Gault formula (1976).

          -  Patients with hepatic dysfunction as defined by increased ALT (alanine
             aminotranferase) / AST (aspartate aminotransferase) > 3 x upper limit of normal (ULN)
             and increased total bilirubin > 3mg/dL [>51.3 µmol/L]).

          -  Patients who receive treatment for a medical condition requiring chronic use of
             systemic steroids.

          -  Treatment with any anti-diabetic medication other than insulin within 4 weeks of
             transplant.

          -  Use of any investigational agent within 12 weeks of enrolment, including
             "anti-inflammatory" strategies (e.g. anti-TNFα, anti-IL-1 RA).

          -  Hypersensitivity to:

               1. ibuprofen or to more than one non steroidal anti-inflammatory drug (NSAID).

               2. medications belonging to the class of sulfonamides, such as sulfamethazine,
                  sulfamethoxazole, sulfasalazine, nimesulide or celecoxib.

          -  Pregnant or breast-feeding women; unwillingness to use effective contraceptive
             measures (females and males).

        Additional exclusion criteria specific for US centre.