Reparixin in Pancreatic Islet Transplantation

NCT01220856 | Completed Phase 2 Results

• 2 other identifiers: REP01102010-019424-31
• Study Type: interventional
• Target: 9
• Locations: 2 countries
• Sites: 2

Brief Summary

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).

Conditions

Pancreatic Islet Transplantation in Type 1 Diabetes Mellitus

Keywords

Islet transplantation; Type 1 diabetes mellitus

Outcome Measures

Primary Outcomes (1)

• The Percentage of Insulin-independent Patients Following Single Infusion Islet Cell Transplantation at Day 75 +/- 5

  Insulin-independence was defined as freedom from the need to take exogenous insulin for 14 or more consecutive days, with adequate glycemic control, as defined by: * HbA1c level of less than 7%; * glucose level after an overnight fast not exceeding 140 mg/dL (7.8 mmol/L) more than 3 times a week (based on measuring capillary glucose level a minimum of 7 times in a 7-day period); * glucose level not exceeding 2-hour postprandial levels of 180 mg/dL (10 mmol/L) more than 4 times a week (based on measuring capillary glucose level a minimum of 21 times in a 7-day period).

  day 75 +/- 5 post-transplant

Other Outcomes (21)

• The Percentage of Insulin-independent Patients Following Islet Cell Transplantation up to One Year After the Last Transplant

  up to one year after the transplant

• Time to Achieve Insulin-independence After the Transplant 2

  up to 1 year after transplant 2

• Total Time of Insulin Independence After the Transplant

  up to 1 year after transplant 2

Study Arms (2)

Reparixin

EXPERIMENTAL

Reparixin + Immunosuppression Reparixin was administered at a dose of 2.772 mg/kg body weight/hour for 7 days (168 hours) at each transplant. It was administered as a continuous IV infusion into a (high-flow) central vein. Investigational Product infusion was to begin approximately 12 hours (range between 6 to 16 hours) before each pancreatic islet infusion was started. The Investigator identified the time to start study drug administration. Reparixin was given to all patients of this arm using the same dosing solution (reparixin 11.00 mg/mL), but the pump rate was adjusted to provide an infusion rate of approximately 0.25 mL/kg/hour. For immunosoppression regimen see the other arm description.

Drug: Reparixin

No experimental intervention

NO INTERVENTION

Immunosuppression only. Induction: First islet infusion: anti-thymocyte globulin (ATG), administered IV (central vein) at the dose of 1.5 mg/kg on Day -1, 0, 1, and 2 of islet infusion. The first ATG injection was preceded by a bolus IV injection of 500 mg methylprednisolone. Induction for the second islet infusion was to be administered per center practice. Maintenance: Mycophenolate mofetil (MMF), administered orally at the dose of 1 g twice a day, starting on Day -1 of the first islet infusion; Tacrolimus, administered orally starting on Day -1 of the first islet infusion at a dose of 0.087 mg/kg twice a day. Thereafter, dosing was to be targeted to blood trough levels of 8 to 10 ng/mL. Administration continued up to Month 3 after the first transplant. Rapamycin was to replace tacrolimus from Month 3 after the first transplant. It was to be administered orally at the starting dose of 0.1 mg/kg once a day, then targeted to a blood trough level of 10 to 12 ng/mL.

Interventions

Reparixin DRUG

Reparixin + immunosuppression

Also known as: REP

Reparixin

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Dompé Farmaceutici S.p.A: lead

Study Sites (2)

University Hospital Carl Gustav Carus Dresden

Dresden, 01307, Germany

Location

Ospedale San Raffaele

Milan, 20132, Italy

Location

Related Publications (2)

• Ajmal N, Bogart MC, Khan P, Max-Harry IM, Healy AM, Nunemaker CS. Identifying Promising Immunomodulators for Type 1 Diabetes (T1D) and Islet Transplantation. J Diabetes Res. 2024 Dec 20;2024:5151171. doi: 10.1155/jdr/5151171. eCollection 2024.

  PMID: 39735417 DERIVED

• Citro A, Cantarelli E, Piemonti L. Anti-inflammatory strategies to enhance islet engraftment and survival. Curr Diab Rep. 2013 Oct;13(5):733-44. doi: 10.1007/s11892-013-0401-0.

  PMID: 23912763 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

reparixin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Luisa Daffonchio, PhD
• Organization: Dompé SpA

daffonchio@dompe.it

+39 583831

Study Officials

• Lorenzo Piemonti, MD

  Fondazione Centro San Raffaele del Monte Tabor - Milan; Italy

  PRINCIPAL INVESTIGATOR

• Barbara Ludwig, MD

  University Hospital Carl Gustav Carus - Dresden; Germany

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2010
• First Posted: October 14, 2010
• Study Start: July 28, 2010
• Primary Completion: April 30, 2013
• Study Completion: April 30, 2013
• Last Updated: March 11, 2021
• Results First Posted: March 11, 2021

Record last verified: 2021-02

Locations

IT (1); DE (1)