Phase 3 N=48 Randomized Double-blind Prevention

Study to Assess Efficacy & Safety of Reparixin in Pancreatic Islet Transplantation

Islet Transplantation in Diabetes Mellitus Type 1

Bottom Line

View on ClinicalTrials.gov: NCT01817959 ↗

Enrolled (actual)

Serious AEs

60.4%

Results posted

Dec 2019

Primary outcome: Primary: 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 — 0.247; 0.321 ng/mL/min — p=0.9863

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Reparixin (Drug); Placebo (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Dompé Farmaceutici S.p.A
Primary completion: Dec 2016

Outcome Measures

Outcome	Result	p-value
PRIMARY 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	0.234; 0.207	0.7115
PRIMARY 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	0.234; 0.207	0.7115
SECONDARY Percentage of Insulin-independent Patients at Day 75	18.5; 5.6; 27.8; 53.3	0.1346
SECONDARY Percentage of Insulin-independent Patients at Day 365	32.0; 31.3	0.9130
SECONDARY Percentage of Patients Who Achieve and Maintain an HbA1c <7.0% (or a Reduction in HbA1c > 2%) AND Are Free of Severe Hypoglycaemic Events After Transplant in the Efficacy Population 1	40.0; 50.0	0.5467
SECONDARY Percentage of Patients Who Did Not Receive a 2nd Islet Infusion	14.8; 0.0	0.1383
SECONDARY Cumulative Number of Severe Hypoglycaemic Events in the Efficacy Population 1	2.88; 3.50	—
SECONDARY Absolute Change From Baseline in Average Daily Insulin Requirements in Efficacy Population 1	-0.231; -0.220; -0.389; -0.463; -0.302; -0.375	0.6952
SECONDARY Percent Change From Baseline in Average Daily Insulin Requirements in Efficacy Population 1	-42.5; -35.0; -74.0; -27.7; -59.4; -63.7	0.5910
SECONDARY Absolute Change in HbA1c % From Pre-transplant Levels in Efficacy Population 1	-1.58; -2.18; -2.04; -2.81; -1.30; -1.87	0.3253
SECONDARY Percent Change in HbA1c % From Pre-transplant Levels in Efficacy Population 1	-18.9; -24.0; -24.4; -30.5; -15.7; -20.9	0.4290
SECONDARY Basal (Fasting) and 0 to 120 Min Time Course of Glucose Derived From the Mixed Meal Tolerance Test (MMTT) in Efficacy Population 1	120.6; 118.9; 146.0; 132.5; 191.6; 168.1	—
SECONDARY Basal (Fasting) and 0 to 120 Min Time Course of C-peptide (Non-normalized) Derived From the MMTT in Efficacy Population 1	0.50; 0.51; 0.71; 0.67; 1.18; 0.89	—
SECONDARY Basal (Fasting) and 0 to 120 Min Time Course of Insulin Derived From the MMTT in Efficacy Population 1	16.5; 15.2; 13.5; 11.8; 21.0; 15.8	—
SECONDARY β-cell Function as Assessed by β-score in Efficacy Population 1	4.19; 4.06; 5.53; 5.67; 4.63; 5.13	0.9949
SECONDARY β-cell Function as Assessed by Transplant Estimated Function (TEF) in Efficacy Population 1	0.523; 0.621; 0.764; 0.981; 0.539; 0.719	0.2444

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) 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:
ibuprofen or to more than one non steroidal anti-inflammatory drug (NSAID).
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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01817959). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.