NCT01817959: REP0211

A Phase 3, Multicenter, Randomized, Double-blind, Parallel Assignment Study to Assess the Efficacy and Safety of Reparixin in Pancreatic Islet Transplantation

Completed Phase 3 Results posted Last updated 21 December 2023

What this trial tests

Phase 3 trial testing Reparixin in Islet Transplantation in Diabetes Mellitus Type 1 in 51 participants. Completed in 1 December 2017.

Timeline

1 October 2012

Primary endpoint
1 December 2016

1 December 2017

Quick facts

Lead sponsor	Dompé Farmaceutici S.p.A
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	prevention
Enrollment	51
Start date	1 October 2012
Primary completion	1 December 2016
Estimated completion	1 December 2017
Sites	9 locations across United States, Czechia, Italy, Sweden, United Kingdom

Drugs / interventions tested

• Reparixin — full drug profile →
• Placebo

Conditions studied

• Islet Transplantation in Diabetes Mellitus Type 1 — all drugs for Islet Transplantation in Diabetes Mellitus Type 1 →

Sponsor

Dompé Farmaceutici S.p.A — full company profile →

Who can join

Adults 18 to 70, any sex, with Islet Transplantation in Diabetes Mellitus Type 1. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• 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: Basal, -15' prior to meal, 15', 30', 60', 90', 120' following meal, Day 75±5 after the 1st islet infusion
  The MMTT was to be performed ideally after an overnight fast. The test was to be initiated before 10 a.m. The Boost Original complete nutritional drink (Nestlé Nutrition) was used for the MMTT. Subjects were given 6 mL/kg of Boost preparation up to a maximum of 360 mL, to be drunk within 5 min. Blood samples for the C-peptide assay (the primary assessment) were withdrawn in fasting condition (basa
• 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: Basal, -15' prior to meal, 15', 30', 60', 90', 120' following meal, Day 365±14 after the last islet infusion
  The MMTT was to be performed ideally after an overnight fast. The test was to be initiated before 10 a.m. The Boost Original complete nutritional drink (Nestlé Nutrition) was used for the MMTT. Subjects were given 6 mL/kg of Boost preparation up to a maximum of 360 mL, to be drunk within 5 min. Blood samples for the C-peptide assay (the primary assessment) were withdrawn in fasting condition (basa

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. The chemokines CXCL8 and CXCL12: molecular and functional properties, role in disease and efforts towards pharmacological intervention.
   Cambier S, Gouwy M, Proost P. · · 2023 · cited 387× · PMID 36725964 · DOI 10.1038/s41423-023-00974-6
2. Multiple Roles for Chemokines in Neutrophil Biology.
   Capucetti A, Albano F, Bonecchi R. · · 2020 · cited 230× · PMID 32733442 · DOI 10.3389/fimmu.2020.01259
3. Pancreatic Islet Transplantation in Humans: Recent Progress and Future Directions.
   Rickels MR, Robertson RP. · · 2019 · cited 212× · PMID 30541144 · DOI 10.1210/er.2018-00154
4. Islet cell transplantation for the treatment of type 1 diabetes: recent advances and future challenges.
   Bruni A, Gala-Lopez B, Pepper AR, Abualhassan NS, et al · · 2014 · cited 159× · PMID 25018643 · DOI 10.2147/dmso.s50789
5. What Do Structures Tell Us About Chemokine Receptor Function and Antagonism?
   Kufareva I, Gustavsson M, Zheng Y, Stephens BS, et al · · 2017 · cited 84× · PMID 28532213 · DOI 10.1146/annurev-biophys-051013-022942
6. Wound healing and cancer stem cells: inflammation as a driver of treatment resistance in breast cancer.
   Arnold KM, Opdenaker LM, Flynn D, Sims-Mourtada J. · · 2015 · cited 84× · PMID 25674014 · DOI 10.4137/cgm.s11286
7. CXCR2 chemokine receptor - a master regulator in cancer and physiology.
   Lazennec G, Rajarathnam K, Richmond A. · · 2024 · cited 53× · PMID 37872025 · DOI 10.1016/j.molmed.2023.09.003
8. Current status of clinical islet transplantation.
   Pepper AR, Gala-Lopez B, Ziff O, Shapiro AJ. · · 2013 · cited 42× · PMID 24392308 · DOI 10.5500/wjt.v3.i4.48