Back to resultsStudy to Assess Efficacy & Safety of Reparixin in Pancreatic Islet Transplantation (REP0211)
Primary Purpose
Islet Transplantation in Diabetes Mellitus Type 1
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Reparixin
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Islet Transplantation in Diabetes Mellitus Type 1 focused on measuring Pancreatic islet transplantation, Diabetes Mellitus Type 1, Islet transplantation graft survival & function
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prior to any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.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) < 60 mL/min according to the Cockcroft-Gault formula (1976).
- Patients with hepatic dysfunction as defined by increased ALT (alanine aminotranferase) / AST (aspartate aminotransferase) > 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.
Sites / Locations
- The University of Chicago Medical Center, Department of Surgery, Division of Abdominal Organ Transplantation
- Institute for Clinical and Experimental Medicine (IKEM), Diabetes Centre; Department of Diabetes.
- Dipartimento di Medicina Interna e Specialistica; IRCCS Ospedale San Raffaele
- S.S.D. Diabetologia, Azienda Ospedaliera Ospedale Niguarda Ca' Granda, Piazza Ospedale Maggiore 3
- Transplant Institute - Sahlgrenska University Hospital
- Department of Nephrology and Transplantation; Skane University Hospital
- Department of Transplantation Surgery; The Karolinska University Hospital
- Division for Transplantation and Liver Surgery; Department of Surgery; Uppsala University Hospital
- Institute of Transplantation, Newcastle upon Tyne Hospitals - NHS Foundation Trust, Freeman Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Reparixin group
Placebo group
Arm Description
Continuous iv infusion
Continuous iv infusion
Outcomes
Primary Outcome Measures
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
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 (basal), just prior to the meal (time 0, within 15 min prior to the meal) and then at 15, 30, 60, 90, 120 min after the meal.
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
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 (basal), just prior to the meal (time 0, within 15 min prior to the meal) and then at 15, 30, 60, 90, 120 min after the meal.
Secondary Outcome Measures
Percentage of Insulin-independent Patients at Day 75
For the purpose of this study, insulin-independence is defined as freedom from the need to take exogenous insulin for 14 or more consecutive days, with adequate glycaemic control, as defined by:
a glycated hemoglobin (HbA1c) level of less than 7%;
a glucose level after an overnight fast not exceeding 140 mg/dL (7.8 mmol/L) more than three times a week (based on measuring capillary glucose level a minimum of 7 times in a 7 day period);
a glucose level not exceeding 2-hour postprandial levels of 180 mg/dL (10 mmol/L) more than four times a week (based on measuring capillary glucose level 14 times in a 7 day period).
Percentage of Insulin-independent Patients at Day 365
For the purpose of this study, insulin-independence is defined as freedom from the need to take exogenous insulin for 14 or more consecutive days, with adequate glycaemic control, as defined by:
a glycated hemoglobin (HbA1c) level of less than 7%;
a glucose level after an overnight fast not exceeding 140 mg/dL (7.8 mmol/L) more than three times a week (based on measuring capillary glucose level a minimum of 7 times in a 7 day period);
a glucose level not exceeding 2-hour postprandial levels of 180 mg/dL (10 mmol/L) more than four times a week (based on measuring capillary glucose level 14 times in a 7 day period).
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
For the purpose of this study, a severe hypoglycaemic event is defined as an event with one of the following symptoms: memory loss, confusion, uncontrollable behavior, irrational behavior, unusual difficulty in awakening, suspected seizure, seizure, loss of consciousness or visual symptoms, in which the subject was unable to treat him/herself and which was associated with either a blood glucose level <54mg/dL (3.0 mmol/L) or prompt recovery after oral carbohydrate, i.v. glucose, or glucagon administration.
Percentage of Patients Who Did Not Receive a 2nd Islet Infusion
This endpoint describes subjects who were not allocated to a 2nd islet infusion because they were insulin independent after the 1st islet infusion.
Cumulative Number of Severe Hypoglycaemic Events in the Efficacy Population 1
The cumulative number of severe hypoglycaemic events after last transplant was assessed. For the purpose of this study, a severe hypoglycaemic event is defined as an event with one of the following symptoms: memory loss, confusion, uncontrollable behaviour, irrational behaviour, unusual difficulty in awakening, suspected seizure, seizure, loss of consciousness or visual symptoms, in which the subject was unable to treat him/herself and which was associated with either a blood glucose level <54 mg/dL (3.0 mmol/L) or prompt recovery after oral carbohydrate, i.v. glucose, or glucagon administration.
Absolute Change From Baseline in Average Daily Insulin Requirements in Efficacy Population 1
Change from baseline is assessed as absolute decrease from pre-transplant levels. For the purpose of this study, daily insulin is averaged over the previous week.
Percent Change From Baseline in Average Daily Insulin Requirements in Efficacy Population 1
Change from baseline is assessed as percentage decrease from pre-transplant levels. For the purpose of this study, daily insulin is averaged over the previous week.
Absolute Change in HbA1c % From Pre-transplant Levels in Efficacy Population 1
Change from baseline in Glycated haemoglobin (HbA1c) was assessed as absolute decrease from pre-transplant levels. Diagnostic standards for HbA1c from American Diabetes Association are: <5.7% Normal; 5.7-6.4% prediabetes; >6.5 diabetes.
Percent Change in HbA1c % From Pre-transplant Levels in Efficacy Population 1
Change from baseline in Glycated haemoglobin (HbA1c) was assessed as percentage decrease from pre-transplant levels. Diagnostic standards for HbA1c from American Diabetes Association are: <5.7% Normal; 5.7-6.4% prediabetes; >6.5 diabetes.
Basal (Fasting) and 0 to 120 Min Time Course of Glucose Derived From the Mixed Meal Tolerance Test (MMTT) in Efficacy Population 1
Glucose levels were measured at the baseline in fasting condition, and at the following timepoints: 15, 30, 60, 90, 120 min after mixed meal at the hereunder reported time frame.
Basal (Fasting) and 0 to 120 Min Time Course of C-peptide (Non-normalized) Derived From the MMTT in Efficacy Population 1
C-peptide levels not normalized by the number of islet equivalent (IEQ)/kg were measured at the baseline in fasting condition, and at the following timepoints: 15, 30, 60, 90, 120 min after mixed meal at the hereunder reported time frame.
Basal (Fasting) and 0 to 120 Min Time Course of Insulin Derived From the MMTT in Efficacy Population 1
Insulin levels were measured at the baseline in fasting condition, and at the following timepoints: 15, 30, 60, 90, 120 min after mixed meal at the hereunder reported time frame.
β-cell Function as Assessed by β-score in Efficacy Population 1
The β-score ranges from 0 (no graft function) to 8 (interpreted as an index of excellent graft function), and gives 0-2 points each for glucose, HbA1C, stimulated C-peptide and insulin requirement. Both for the total and partial scores the higher the score, the better the outcome.
Fasting plasma glucose (mg/dL): ≤99 (Score 2); 100 - 124 (Score 1); ≥125 (Score 0); HbA1c (%): ≤6.1(Score 2); 6.2 - 6.9 (Score 1); ≥ 7.0 (Score 0); Daily average (previous week) insulin (IU/kg/day): --- (Score 2); 0.01 - 0.24 (score 1); ≥ 0.25 (Score 0) Stimulated C-peptide (ng/mL): ≥ 0.9; 0.3 - 0.89; ≤0.3
β-cell Function as Assessed by Transplant Estimated Function (TEF) in Efficacy Population 1
TEF selects the two pivotal components of the β-score (DIR and A1C) and links them together through a simple description of how insulin supply influences the patient's glycemic control.
TEF was evaluated by the following equation: TEF = a.DIR + b.HbA1c + c where DIR = daily insulin requirement (average in the previous week); a = -1; b = 1/-5.43; c = -a.DIR (pre-transplant) - b.HbA1c (pre-transplant)
Full Information
NCT ID
NCT01817959
First Posted
March 7, 2013
Last Updated
September 23, 2021
Sponsor
Dompé Farmaceutici S.p.A
1. Study Identification
Unique Protocol Identification Number
NCT01817959
Brief Title
Study to Assess Efficacy & Safety of Reparixin in Pancreatic Islet Transplantation
Acronym
REP0211
Official Title
A Phase 3, Multicenter, Randomized, Double-blind, Parallel Assignment Study to Assess the Efficacy and Safety of Reparixin in Pancreatic Islet Transplantation
Study Type
Interventional
2. Study Status
Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
October 2012 (undefined)
Primary Completion Date
December 2016 (Actual)
Study Completion Date
December 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Dompé Farmaceutici S.p.A
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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.
Detailed Description
Pancreatic islet transplantation has become a feasible option in the treatment of T1D which offers advantages over whole pancreas transplantation.
Several strategies are being evaluated, including anti-TNFα, aimed to prevent early inflammatory events that limit islet engraftment. Among possible mechanisms CXCL8 could play a crucial role in triggering the inflammatory reaction and might represent a relevant therapeutic target to prevent early graft failure.
Preliminary data obtained in transplanted patients recruited in the ongoing pilot trial coupled with the safety shown in human phase 1 and 2 studies provide a sound rationale for further development of reparixin in islet transplantation and prompted the conduct of this phase 3 clinical, multicentre, randomised, double-blind, parallel assignment study aimed at assessing the efficacy and safety of reparixin in preventing graft dysfunction after islet transplantation in T1D subjects.
At least 42 patients receiving pancreatic islet transplant were involved. Patients might receive up to 2 islet transplants, with the second transplant on average 6 months after the first one. Patients were randomly (2:1) assigned to receive either reparixin or placebo (control group). The Investigational Product was administered as an added on treatment to the immunosuppressant regimen.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Islet Transplantation in Diabetes Mellitus Type 1
Keywords
Pancreatic islet transplantation, Diabetes Mellitus Type 1, Islet transplantation graft survival & function
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
51 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Reparixin group
Arm Type
Experimental
Arm Description
Continuous iv infusion
Arm Title
Placebo group
Arm Type
Placebo Comparator
Arm Description
Continuous iv infusion
Intervention Type
Drug
Intervention Name(s)
Reparixin
Other Intervention Name(s)
REP
Intervention Description
Continuous i.v. infusion into a central vein for 7 days, starting approximately 12 hrs (6-18 hrs) before each pancreatic islet infusion.The Investigational Product (IP) were to be administered as an add-on treatment for the immunosuppressant regimen.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Continuous infusion at a volume/rate matching active treatment.The placebo was to be administered as well as an add-on treatment for the immunosuppressant regimen.
Primary Outcome Measure Information:
Title
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
Description
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 (basal), just prior to the meal (time 0, within 15 min prior to the meal) and then at 15, 30, 60, 90, 120 min after the meal.
Time Frame
Basal, -15' prior to meal, 15', 30', 60', 90', 120' following meal, Day 75±5 after the 1st islet infusion
Title
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
Description
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 (basal), just prior to the meal (time 0, within 15 min prior to the meal) and then at 15, 30, 60, 90, 120 min after the meal.
Time Frame
Basal, -15' prior to meal, 15', 30', 60', 90', 120' following meal, Day 365±14 after the last islet infusion
Secondary Outcome Measure Information:
Title
Percentage of Insulin-independent Patients at Day 75
Description
For the purpose of this study, insulin-independence is defined as freedom from the need to take exogenous insulin for 14 or more consecutive days, with adequate glycaemic control, as defined by:
a glycated hemoglobin (HbA1c) level of less than 7%;
a glucose level after an overnight fast not exceeding 140 mg/dL (7.8 mmol/L) more than three times a week (based on measuring capillary glucose level a minimum of 7 times in a 7 day period);
a glucose level not exceeding 2-hour postprandial levels of 180 mg/dL (10 mmol/L) more than four times a week (based on measuring capillary glucose level 14 times in a 7 day period).
Time Frame
Day 75±5 after the 1st and 2nd islet infusion
Title
Percentage of Insulin-independent Patients at Day 365
Description
For the purpose of this study, insulin-independence is defined as freedom from the need to take exogenous insulin for 14 or more consecutive days, with adequate glycaemic control, as defined by:
a glycated hemoglobin (HbA1c) level of less than 7%;
a glucose level after an overnight fast not exceeding 140 mg/dL (7.8 mmol/L) more than three times a week (based on measuring capillary glucose level a minimum of 7 times in a 7 day period);
a glucose level not exceeding 2-hour postprandial levels of 180 mg/dL (10 mmol/L) more than four times a week (based on measuring capillary glucose level 14 times in a 7 day period).
Time Frame
Day 365±14 after last islet infusion
Title
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
Description
For the purpose of this study, a severe hypoglycaemic event is defined as an event with one of the following symptoms: memory loss, confusion, uncontrollable behavior, irrational behavior, unusual difficulty in awakening, suspected seizure, seizure, loss of consciousness or visual symptoms, in which the subject was unable to treat him/herself and which was associated with either a blood glucose level <54mg/dL (3.0 mmol/L) or prompt recovery after oral carbohydrate, i.v. glucose, or glucagon administration.
Time Frame
HbA1c at Day 365±14 after the last islet infusion; severe hypoglycaemic events from Day 75 to Day 365 after the last islet infusion
Title
Percentage of Patients Who Did Not Receive a 2nd Islet Infusion
Description
This endpoint describes subjects who were not allocated to a 2nd islet infusion because they were insulin independent after the 1st islet infusion.
Time Frame
Day 365±14 after the 1st islet infusion
Title
Cumulative Number of Severe Hypoglycaemic Events in the Efficacy Population 1
Description
The cumulative number of severe hypoglycaemic events after last transplant was assessed. For the purpose of this study, a severe hypoglycaemic event is defined as an event with one of the following symptoms: memory loss, confusion, uncontrollable behaviour, irrational behaviour, unusual difficulty in awakening, suspected seizure, seizure, loss of consciousness or visual symptoms, in which the subject was unable to treat him/herself and which was associated with either a blood glucose level <54 mg/dL (3.0 mmol/L) or prompt recovery after oral carbohydrate, i.v. glucose, or glucagon administration.
Time Frame
Day 365±14 after the last islet infusion
Title
Absolute Change From Baseline in Average Daily Insulin Requirements in Efficacy Population 1
Description
Change from baseline is assessed as absolute decrease from pre-transplant levels. For the purpose of this study, daily insulin is averaged over the previous week.
Time Frame
Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion
Title
Percent Change From Baseline in Average Daily Insulin Requirements in Efficacy Population 1
Description
Change from baseline is assessed as percentage decrease from pre-transplant levels. For the purpose of this study, daily insulin is averaged over the previous week.
Time Frame
Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion
Title
Absolute Change in HbA1c % From Pre-transplant Levels in Efficacy Population 1
Description
Change from baseline in Glycated haemoglobin (HbA1c) was assessed as absolute decrease from pre-transplant levels. Diagnostic standards for HbA1c from American Diabetes Association are: <5.7% Normal; 5.7-6.4% prediabetes; >6.5 diabetes.
Time Frame
Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion
Title
Percent Change in HbA1c % From Pre-transplant Levels in Efficacy Population 1
Description
Change from baseline in Glycated haemoglobin (HbA1c) was assessed as percentage decrease from pre-transplant levels. Diagnostic standards for HbA1c from American Diabetes Association are: <5.7% Normal; 5.7-6.4% prediabetes; >6.5 diabetes.
Time Frame
Day 75±5 after the 1st and 2nd islet infusion and day 365+14 after last islet infusion
Title
Basal (Fasting) and 0 to 120 Min Time Course of Glucose Derived From the Mixed Meal Tolerance Test (MMTT) in Efficacy Population 1
Description
Glucose levels were measured at the baseline in fasting condition, and at the following timepoints: 15, 30, 60, 90, 120 min after mixed meal at the hereunder reported time frame.
Time Frame
Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion
Title
Basal (Fasting) and 0 to 120 Min Time Course of C-peptide (Non-normalized) Derived From the MMTT in Efficacy Population 1
Description
C-peptide levels not normalized by the number of islet equivalent (IEQ)/kg were measured at the baseline in fasting condition, and at the following timepoints: 15, 30, 60, 90, 120 min after mixed meal at the hereunder reported time frame.
Time Frame
Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion
Title
Basal (Fasting) and 0 to 120 Min Time Course of Insulin Derived From the MMTT in Efficacy Population 1
Description
Insulin levels were measured at the baseline in fasting condition, and at the following timepoints: 15, 30, 60, 90, 120 min after mixed meal at the hereunder reported time frame.
Time Frame
Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion
Title
β-cell Function as Assessed by β-score in Efficacy Population 1
Description
The β-score ranges from 0 (no graft function) to 8 (interpreted as an index of excellent graft function), and gives 0-2 points each for glucose, HbA1C, stimulated C-peptide and insulin requirement. Both for the total and partial scores the higher the score, the better the outcome.
Fasting plasma glucose (mg/dL): ≤99 (Score 2); 100 - 124 (Score 1); ≥125 (Score 0); HbA1c (%): ≤6.1(Score 2); 6.2 - 6.9 (Score 1); ≥ 7.0 (Score 0); Daily average (previous week) insulin (IU/kg/day): --- (Score 2); 0.01 - 0.24 (score 1); ≥ 0.25 (Score 0) Stimulated C-peptide (ng/mL): ≥ 0.9; 0.3 - 0.89; ≤0.3
Time Frame
Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion
Title
β-cell Function as Assessed by Transplant Estimated Function (TEF) in Efficacy Population 1
Description
TEF selects the two pivotal components of the β-score (DIR and A1C) and links them together through a simple description of how insulin supply influences the patient's glycemic control.
TEF was evaluated by the following equation: TEF = a.DIR + b.HbA1c + c where DIR = daily insulin requirement (average in the previous week); a = -1; b = 1/-5.43; c = -a.DIR (pre-transplant) - b.HbA1c (pre-transplant)
Time Frame
Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion
Other Pre-specified Outcome Measures:
Title
Frequency of Patients Positive/Negative for Autoantibodies Against Glutamic Acid Decarboxylase (GAD) in Efficacy Population 1
Description
Auto-antibodies were assayed on cell-free serum samples obtained as per centre practice ideally by immunoprecipitation of recombinant antigens. The Luminescent Immuno-Precipitation System based on chimeric autoantigens fused to luciferase enzyme was suggested as the preferred method to be used. Luciferase activity was measured in recovered immune-complex.
Time Frame
At pre-transplant, Day 75±5 after the 1st and 2nd islet infusion and Day 365±14 days after the last islet infusion
Title
Frequency of Patients Positive/Negative for Autoantibodies Against Islet Antigen-2 (IA-2) in Efficacy Population 1
Description
Auto-antibodies were assayed on cell-free serum samples obtained as per centre practice ideally by immunoprecipitation of recombinant antigens. The Luminescent Immuno-Precipitation System based on chimeric autoantigens fused to luciferase enzyme was suggested as the preferred method to be used. Luciferase activity was measured in recovered immune-complex.
Time Frame
At pre-transplant, Day 75±5 after the 1st and 2nd islet infusion and Day 365±14 days after the last islet infusion,
Title
Frequency of Patients Positive/Negative for Autoantibodies Against Class I Human Leucocyte Antigen (HLA) in Efficacy Population 1
Description
Anti-HLA antibodies were assayed on cell-free serum samples obtained as per centre practice ideally by the Luminex analyzer. Class I and II positive/negative results were recorded.
Time Frame
Pre-transplant, day 75±5 after the 1st and 2nd islet infusion and day 365±14 after the last islet infusion
Title
Frequency of Patients Positive/Negative for Autoantibodies Against Class II Human Leucocyte Antigen (HLA) in Efficacy Population 1
Description
Anti-HLA antibodies were assayed on cell-free serum samples obtained as per centre practice ideally by the Luminex analyzer. Class I and II positive/negative results were recorded.
Time Frame
At pre-transplant, Day 75±5 after the 1st and 2nd islet infusion and Day 365±14 days after the last islet infusion,
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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) < 60 mL/min according to the Cockcroft-Gault formula (1976).
Patients with hepatic dysfunction as defined by increased ALT (alanine aminotranferase) / AST (aspartate aminotransferase) > 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lorenzo PIEMONTI, MD
Organizational Affiliation
Dipartimento di Medicina Interna e Specialistica; IRCCS Ospedale San Raffaele
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Torbjörn LUNDGREN, MD, PhD
Organizational Affiliation
Department of Transplantation Surgery; The Karolinska University Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Gunnar TUFVESON, Professor
Organizational Affiliation
Department of Surgery; Uppsala University Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ehab RAFAEL, MD, PhD
Organizational Affiliation
Department of Nephrology and Transplantation; Skane University Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
James SHAW, Professor
Organizational Affiliation
Institute of Transplantation, Newcastle upon Tyne Hospitals - Freeman Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Frantisek SAUDEK, MD, DrSc
Organizational Affiliation
Institute for Clinical and Experimental Medicine (IKEM), Department of Diabetes.
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Piotr WITKOWSKI, MD, PhD
Organizational Affiliation
The University of Chicago Medical Center, Department of Surgery
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Federico BERTUZZI, MD
Organizational Affiliation
S.S.D. Diabetologia, Azienda Ospedaliera Ospedale Niguarda Ca' Granda, Milano
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Bengt GUSTAFSSON, MD, PhD
Organizational Affiliation
Transplant Institute - Sahlgrenska University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
The University of Chicago Medical Center, Department of Surgery, Division of Abdominal Organ Transplantation
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Institute for Clinical and Experimental Medicine (IKEM), Diabetes Centre; Department of Diabetes.
City
Praha
ZIP/Postal Code
14021
Country
Czechia
Facility Name
Dipartimento di Medicina Interna e Specialistica; IRCCS Ospedale San Raffaele
City
Milan
ZIP/Postal Code
20132
Country
Italy
Facility Name
S.S.D. Diabetologia, Azienda Ospedaliera Ospedale Niguarda Ca' Granda, Piazza Ospedale Maggiore 3
City
Milan
ZIP/Postal Code
20162
Country
Italy
Facility Name
Transplant Institute - Sahlgrenska University Hospital
City
Göteborg
ZIP/Postal Code
41345
Country
Sweden
Facility Name
Department of Nephrology and Transplantation; Skane University Hospital
City
Malmö
ZIP/Postal Code
20502
Country
Sweden
Facility Name
Department of Transplantation Surgery; The Karolinska University Hospital
City
Stockholm
ZIP/Postal Code
14186
Country
Sweden
Facility Name
Division for Transplantation and Liver Surgery; Department of Surgery; Uppsala University Hospital
City
Uppsala
ZIP/Postal Code
75185
Country
Sweden
Facility Name
Institute of Transplantation, Newcastle upon Tyne Hospitals - NHS Foundation Trust, Freeman Hospital
City
Newcastle upon Tyne
ZIP/Postal Code
NE7 7DN
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
33908301
Citation
Bachul PJ, Golab K, Basto L, Zangan S, Pyda JS, Perez-Gutierrez A, Borek P, Wang LJ, Tibudan M, Tran DK, Anteby R, Generette GS, Chrzanowski J, Fendler W, Perea L, Jayant K, Lucander A, Thomas C, Philipson L, Millis JM, Fung J, Witkowski P. Post-Hoc Analysis of a Randomized, Double Blind, Prospective Study at the University of Chicago: Additional Standardizations of Trial Protocol are Needed to Evaluate the Effect of a CXCR1/2 Inhibitor in Islet Allotransplantation. Cell Transplant. 2021 Jan-Dec;30:9636897211001774. doi: 10.1177/09636897211001774.
Results Reference
derived
PubMed Identifier
32019854
Citation
Maffi P, Lundgren T, Tufveson G, Rafael E, Shaw JAM, Liew A, Saudek F, Witkowski P, Golab K, Bertuzzi F, Gustafsson B, Daffonchio L, Ruffini PA, Piemonti L; REP0211 Study Group. Targeting CXCR1/2 Does Not Improve Insulin Secretion After Pancreatic Islet Transplantation: A Phase 3, Double-Blind, Randomized, Placebo-Controlled Trial in Type 1 Diabetes. Diabetes Care. 2020 Apr;43(4):710-718. doi: 10.2337/dc19-1480. Epub 2020 Feb 4.
Results Reference
derived
Learn more about this trial
Study to Assess Efficacy & Safety of Reparixin in Pancreatic Islet Transplantation
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