Overview

This trial is active, not recruiting.

Condition islet transplantation in diabetes mellitus type 1,
Treatments reparixin, placebo
Phase phase 3
Sponsor Dompé Farmaceutici S.p.A
Start date October 2012
End date October 2016
Trial size 42 participants
Trial identifier NCT01817959, 2011-006201-10, REP0211

Summary

The chemokine CXCL8 plays a key role in the recruitment and activation of polymorphonuclear neutrophils in post-ischemia reperfusion injury after organ transplantion. 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 type 1 diabetes (T1D) patients.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose prevention
Arm
(Experimental)
Continuous iv infusion
reparixin
Continuous i.v. infusion into a central vein for 7 days, starting approximately 12 hrs (6-18 hrs) before each pancreatic islet infusion.
(Placebo Comparator)
Continuous iv infusion
placebo
Continuous infusion at a volume/rate matching active treatment.

Primary Outcomes

Measure
Area Under the Curve (AUC) for the serum C-peptide level during the first 2 hours of an MMTT (Mixed Meal Tolerance Test), normalized by the number of Islet Equivalent (IEQ)/kg
time frame: Day 75+5 after the 1st islet infusion and day 365+14 after the last islet infusion

Secondary Outcomes

Measure
Proportion of insulin-independent patients
time frame: Day 75+5 after the 1st and 2nd islet infusion and day 365+14 after last islet infusion
Proportion of patients who achieve and maintain an HbA1c <7.0% (or o reduction in HbA1c > 2%) AND are free of severe hypoglycaemic events
time frame: Day 365+14 after the last islet infusion
Proportion of patients receiving a 2nd islet infusion
time frame: Day 365+14 after the 1st islet infusion
Cumulative number of severe hypoglycaemic events
time frame: Day 365+14 after the last islet infusion
Change in average daily insulin requirements (absolute decrease from pre-transplant levels and % decrease from pre-transplant levels).
time frame: Day 75+5 after the 1st and 2nd islet infusion and day 365+14 after last islet infusion
HbA1c % (absolute decrease from pre-transplant levels and % decrease from pre-transplant levels).
time frame: Day 75+5 after the 1st and 2nd islet infusion and day 365+14 after last islet infusion
Basal (fasting) and 0 to 120 min time course of glucose, C-peptide and insulin derived from the MMTT
time frame: Day 75+5 after the 1st and 2nd islet infusion and day 365+14 after last islet infusion
β-cell function as assessed by β-score and Transplant Estimated Function (TEF)
time frame: Day 75+5 after the 1st and 2nd islet infusion and day 365+14 after last islet infusion
Incidence and severity of Adverse Events and Serious Adverse Events
time frame: Throughout the study up to day 365+14 after last islet infusion
Changes in standard laboratory parameters, as a measure of safety
time frame: Pre-infusion hospital admission and post-infusion hospital discharge
Changes in vital signs, as a measure of safety
time frame: Day 0 (hospital admission), day 7 (hospital discharge), ±365 days after the 1st and 2nd islet infusion
ALT/AST, PT/PTT, fibrin degradation products (XDPs), C-reactive protein (CRP)
time frame: All daily up to day 6 after the 1st and 2nd islet infusion; ALT/AST also on day 75+5 after the 1st and 2nd islet infusion

Eligibility Criteria

Male or female participants from 18 years up to 70 years old.

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/AST > 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.

Additional Information

Official title A Phase 3, Multicenter, Randomized, Double-blind, Parallel Assignment Study to Assess the Efficacy and Safety of Reparixin in Pancreatic Islet Transplantation
Principal investigator Lorenzo PIEMONTI, MD
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 study aimed at assessing the efficacy and safety of reparixin in preventing graft dysfunction after islet transplantation in T1D patients. At least 42 patients receiving pancreatic islet transplant will be involved. Patients may receive up to 2 islet transplants, with the second transplant on average 6 months after the first one. Patients will be randomly (2:1) assigned to receive either reparixin or placebo (control group). The Investigational Products will be administered as an added on treatment to the immunosuppressant regimen.
Trial information was received from ClinicalTrials.gov and was last updated in July 2015.
Information provided to ClinicalTrials.gov by Dompé Farmaceutici S.p.A.