CLINICAL TRIALS PROFILE FOR REPARIXIN

Clinical Trials for Reparixin

Trial ID	Title	Status	Sponsor	Phase	Summary
NCT00248040 ↗	Reparixin in Prevention of Delayed Graft Function After Kidney Transplantation	Completed	Dompé Farmaceutici S.p.A	Phase 2	The chemokine CXCL8 plays a key role in the recruitment and activation of polymorphonuclear neutrophils in post-ischemia reperfusion injury after solid organ transplantation. Reparixin is a novel, specific inhibitor of CXCL8. This study is configured to explore the safety and efficacy of reparixin in preventing the delayed graft function (DGF) after kidney transplantation.
NCT01220856 ↗	Reparixin in Pancreatic Islet Transplantation	Completed	Dompé Farmaceutici S.p.A	Phase 2	Inhibition of CXCL8 activity might represent a relevant therapeutic target to prevent injury occurring after pancreatic islet transplantation. Reparixin is a novel and specific inhibitor of CXCL8. This study is designed to explore the efficacy of reparixin in preventing graft dysfunction after islet transplantation in type 1 diabetes patients (T1D).
NCT01817959 ↗	Study to Assess Efficacy & Safety of Reparixin in Pancreatic Islet Transplantation	Completed	Dompé Farmaceutici S.p.A	Phase 3	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.
NCT01861054 ↗	Pilot Study to Evaluate Safety & Biological Effects of Orally Administered Reparixin in Early Breast Cancer	Terminated	Dompé Farmaceutici S.p.A	Phase 2	This is a pilot "window of opportunity" clinical study in patients with operable breast cancer investigating use of reparixin as single agent in the time period between clinical diagnosis and surgery. The primary objectives of this study were: 1- to evaluate the effects of orally administered reparixin on CSCs in the primary tumor and the tumoral microenvironment in an early breast cancer population: A. CSC were measured in tissue samples by techniques that could include: ALDEFLUOR assay and assessment of CD44/CD24 by flow cytometry, or examination of RNA transcripts by RT-PCR, aldehyde dehydrogenase-1, CD44/CD24 and epithelial mesenchymal transition markers (Snail, Twist, Notch) by immunohistochemistry (IHC). CSC were defined as ALDEFLUOR positive (ALDH-1+) and/or CD44 high/CD24 low by flow cytometry or RT-PCR and IHC and by the detection of ALDH-1+ cells with or without epithelial mesenchymal transition (EMT) transcription factor in IHC assays. B. Serine-threonine protein kinase (AKT), focal adhesion kinase (FAK), phosphatase and tensin homolog (PTEN) and chemokine receptor-1 (CXCR1) levels were measured in tissue samples by IHC. C. Measurement of markers of inflammation (interleukin-1beta [IL-1β], interleukin-6 [IL-6], interleukin-8 [IL-8], tumor necrosis factor-alpha [TNF-α], granulocyte macrophage colony stimulating factor [GM-CSF], vascular endothelial growth factor [VEGF], basic fibroblast growth factor [b-FGF] and high-sensitivity C-reactive protein [hsCRP]) in plasma, leukocyte subsets (enumerate T subsets, B, and natural killer/natural killer T [NK/NKT] cells) and study polymorphonuclear leukocyte [PMN] biology in peripheral blood samples. D. Measurement of markers of angiogenesis (CD31 staining), tumor-infiltrating leukocytes (CD4, CD8, NK and macrophages), autophagy (P62 and LC3 by IHC), EpCAM and EMT markers (CD326, CD45, Twist1, SNAIL1, SLUG, ZEB1, FOXC2, TG2, Akt2, P13k and CK19 by RT-PCR) and tissue cellularity (residual disease characterization in tumor bed) in tumor tissue samples. 2. To evaluate the safety of oral reparixin administered three times daily (t.i.d.) for 21 consecutive days. The secondary objective was to define the pharmacokinetic (PK) profile of orally administered reparixin.
NCT01967888 ↗	Efficacy and Safety of Reparixin in Pancreatic Islet Auto-transplantation	Completed	Dompé Farmaceutici S.p.A	Phase 2/Phase 3	The study is a phase 2/3, multicenter, double-blind, parallel assignment study. It involves 100 adult recipients of an intra-hepatic pancreatic Islet Auto-Transplantation (IAT). The objective of this clinical trial is to assess whether reparixin leads to improved transplant outcome as measured by the proportion of insulin-independent patients following IAT. The safety of reparixin in the specific clinical setting will be also evaluated.
NCT02001974 ↗	Pilot Study to Evaluate Reparixin With Weekly Paclitaxel in Patients With HER 2 Negative Metastatic Breast Cancer (MBC)	Completed	PRA Health Sciences	Phase 1	This is a phase I study to evaluate the safety and define the pharmacokinetic (PK) profile of orally administered reparixin in combination with paclitaxel in HER 2 (Human epidermal growth factor receptor-2) negative metastatic breast cancer patients. The primary objective of this study was to evaluate the safety and define the pharmacokinetic (PK) profile of orally administered reparixin in combination with paclitaxel in HER-2 negative MBC patients. The secondary objectives were to: 1. Evaluate the effects of orally administered reparixin on cancer stem cell (CSC) markers, the tumoral microenvironment and markers of cytokine inflammation; 2. Evaluate peripheral blood samples for enumeration of circulating tumor cells (CTCs), molecular characterization as CSCs and perform epithelial-mesenchymal transition (EMT) biomarker profiling; 3. Assess disease response for indication of efficacy.

Clinical Trial Conditions for Reparixin

Condition Name

Condition Name for
Intervention	Trials
Metastatic Breast Cancer	2
Pancreatectomy for Chronic Pancreatitis	1
Early Allograft Dysfunction	1
Pancreatic Islet Transplantation in Type 1 Diabetes Mellitus	1

Condition MeSH

Condition MeSH for
Intervention	Trials
Breast Neoplasms	4
Pneumonia	3
COVID-19	3
Ischemia	2

Clinical Trial Locations for Reparixin

Trials by Country

Trials by Country for
Location	Trials
United States	44
Italy	7
Russian Federation	3
Spain	3
Germany	2

Trials by US State

Trials by US State for
Location	Trials
Pennsylvania	5
Tennessee	3
New York	3
Illinois	3
Minnesota	3

Clinical Trial Progress for Reparixin

Clinical Trial Phase

Clinical Trial Phase for
Clinical Trial Phase	Trials
Phase 3	3
Phase 2/Phase 3	2
Phase 2	8

Clinical Trial Status

Clinical Trial Status for
Clinical Trial Phase	Trials
Completed	7
Not yet recruiting	4
Terminated	2

Clinical Trial Sponsors for Reparixin

Sponsor Name

Sponsor Name for
Sponsor	Trials
Dompé Farmaceutici S.p.A	13
PRA Health Sciences	2
Novartis	1

Sponsor Type

Sponsor Type for
Sponsor	Trials
Industry	16
Other	1