Reparixin in Pancreatic Islet Transplantation

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT01220856
• Date of registration: 07/10/2010
• Prospective Registration: No
• Primary sponsor: Dompé Farmaceutici S.p.A
• Public title: Reparixin in Pancreatic Islet Transplantation
• Scientific title: A Phase 2 Multicenter, Randomized, Open Label, Parallel Assignment, Pilot Study to Assess the Efficacy and Safety of Reparixin Following Islet Transplantation in Patients With Type 1 Diabetes Mellitus
• Date of first enrolment: July 2010
• Target sample size: 9
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT01220856
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 2

Countries of recruitment

Germany, Italy

Contacts

• Name: Barbara Ludwig, MD
• Affiliation: University Hospital Carl Gustav Carus - Dresden; Germany

• Name: Lorenzo Piemonti, MD
• Affiliation: Fondazione Centro San Raffaele del Monte Tabor - Milan; Italy

Key inclusion & exclusion criteria

Inclusion criteria:

- Ages 18-65 years, inclusive.

- Patients eligible for pancreatic islet transplantation based on local accepted
practice and guidelines. This includes at least: a)clinical history compatible with
T1D with insulin-dependence for >5 years; b) undetectable stimulated (arginine or
MMTT) C-peptide levels (<0.3 ng/mL) in the 12 months before transplant. Sites will
comply with any additional or more stringent criteria locally accepted, as per centre
practice.

- Patients with adequate renal reserve as per calculated creatinine clearance (CLcr) >
60 mL/min according to the Cockcroft-Gault formula (1976).

- Planned intrahepatic islet transplantation alone from a non-living donor with brain
death.

- Planned infusion of 4000 to 7000 islet equivalent (IEQ)/kg body weight.

- Patients willing and able to comply with the protocol procedures for the duration of
the study, including scheduled follow-up visits and examinations.

- Patients 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part of normal medical care, with the understanding that consent may be withdrawn by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, except from recipients of a previous
pancreatic islet transplantation that has failed, are off immunosuppression since at
least 1 year and have negative anti-HLA.

- Recipients of islet from a non-heart beating donor.

- A body mass index >30 kg/m2 or patient weight <45 kg.

- Pre-transplant average daily insulin requirement >1 IU/kg/day.

- Pre-transplant HbA1c >11%.

- Patients with hepatic dysfunction as defined by increased ALT/AST > 3 x ULN and
increased total bilirubin > 3mg/dL [>51.3 micromol/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 4 weeks of enrolment.

- Hypersensitivity to:

- ibuprofen or to more than one non steroidal anti-inflammatory drug

- 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).

Sites will comply with any additional exclusion criteria locally accepted, as per centre
practice.



Age minimum: 18 Years
Age maximum: 65 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Pancreatic Islet Transplantation in Type 1 Diabetes Mellitus

Intervention(s)

Drug: Reparixin

Primary Outcome(s)

Beta-cell function as assessed by beta-score and Transplant Estimated Function [Time Frame: month 1-3-6-12 post- transplant]

The proportion of insulin-independent patients following a single donor-single islet cell transplantation [Time Frame: day 75 +/- 5 post-transplant]

The proportion of patients free of hypoglycaemic events with reduced awareness [Time Frame: month 1-3-6-12 post- transplant]

The proportion of patients free of severe hypoglycaemic events [Time Frame: month 1-3-6-12 post- transplant]

Change in average daily insulin requirements (absolute and % decrease from pre-transplant levels) [Time Frame: month 1-3-6-12 post- transplant]

The proportion of insulin-independent patients after a single donor-single islet cell transplantation [Time Frame: up to one year after the transplant]

HbA1c (absolute and % decrease from pre-transplant levels) [Time Frame: month 1-3-6-12 post- transplant]

Basal (fasting) and -10 to 120 min time course of glucose, C-peptide and insulin derived from the mixed meal tolerance test [Time Frame: month 1-3-6-12 post- transplant]

Time to achieve insulin-independence after the transplant [Time Frame: up to 1 year after the transplant]

Total time of insulin independence after the transplant [Time Frame: up to 1 year after the transplant]

Secondary Outcome(s)

ALT/AST [Time Frame: month 1-3 post-transplant]

Plasma levels of reparixin and its major metabolite [Time Frame: day 3 and day 7 of drug infusion]

Standard laboratory tests (hematology, clinical chemistry, coagulation) [Time Frame: day -1 pre-transplant]

ALT/AST, PT/PTT, fibrin degradation products, C-reactive protein [Time Frame: daily up to day 6 post-transplant]

Standard laboratory tests (hematology, clinical chemistry, coagulation) [Time Frame: day 6/7 post-transplant]

Blood pressure and heart rate [Time Frame: day -1 pre-transplant]

Time course of inflammatory chemokines/cytokines [Time Frame: 6-12-24--72-120-168 hrs after islet infusion]

Auto-antibodies and anti-HLA antibodies [Time Frame: day 6/7 post- transplant; month 1-3-6-12 post- transplant]

Blood pressure and heart rate [Time Frame: day 6/7 post-transplant]

Auto-antibodies and anti-HLA antibodies [Time Frame: day -1 pre-transplant]

Incidence and severity of Adverse Events and Serious Adverse Events [Time Frame: up to 1 year after transplant]

Time course of inflammatory chemokines/cytokines [Time Frame: day -1 pre-transplant]

Secondary ID(s)

REP0110

2010-019424-31

Source(s) of Monetary Support

Please refer to primary and secondary sponsors