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Study to Assess Efficacy & Safety of Reparixin in Pancreatic Islet Transplantation (REP0211)

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ClinicalTrials.gov Identifier: NCT01817959
Recruitment Status : Completed
First Posted : March 26, 2013
Results First Posted : December 18, 2019
Last Update Posted : February 25, 2021
Sponsor:
Information provided by (Responsible Party):
Dompé Farmaceutici S.p.A

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Condition Islet Transplantation in Diabetes Mellitus Type 1
Interventions Drug: Reparixin
Drug: Placebo
Enrollment 51
Recruitment Details  
Pre-assignment Details A total of 51 subjects were randomised into the trial. Three of these subjects did not have a transplant and never received randomised medication. Hence, a total of 48 subjects took trial medication and were included in the Safety Population.
Arm/Group Title Reparixin Group Placebo Group
Hide Arm/Group Description

Continuous iv infusion

Reparixin: 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.

Continuous iv infusion

Placebo: 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.

Period Title: Overall Study
Started 29 19
Completed 25 16
Not Completed 4 3
Reason Not Completed
Graft loss             1             1
forbidden medication             1             1
Adverse Event             1             0
Patient didn't proceed to 1st Islet Inf             1             1
Arm/Group Title Reparixin Group Placebo Group Total
Hide Arm/Group Description

Continuous iv infusion

Reparixin: 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.

Continuous iv infusion

Placebo: 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.

Total of all reporting groups
Overall Number of Baseline Participants 29 19 48
Hide Baseline Analysis Population Description
safety population: A total of 48 subjects (29 Reparixin, 19 placebo) received trial medication and therefore were included in the Safety Population.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 19 participants 48 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
28
  96.6%
18
  94.7%
46
  95.8%
>=65 years
1
   3.4%
1
   5.3%
2
   4.2%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 29 participants 19 participants 48 participants
47.3  (11.3) 42.6  (10.8) 45.5  (11.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 19 participants 48 participants
Female
17
  58.6%
12
  63.2%
29
  60.4%
Male
12
  41.4%
7
  36.8%
19
  39.6%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 29 participants 19 participants 48 participants
Sweden 7 6 13
Czechia 5 3 8
United States 8 4 12
Italy 7 5 12
United Kingdom 2 1 3
1.Primary Outcome
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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).
Arm/Group Title Reparixin Group Placebo Group
Hide Arm/Group Description:

Continuous iv infusion

Reparixin: 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.

Continuous iv infusion

Placebo: 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.

Overall Number of Participants Analyzed 27 18
Mean (Standard Deviation)
Unit of Measure: ng/mL/min
0.247  (0.218) 0.321  (0.208)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reparixin Group, Placebo Group
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9863
Comments Treatment p value
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least square mean difference
Estimated Value 0.001
Confidence Interval (2-Sided) 99.75%
-0.205 to 0.207
Estimation Comments [Not Specified]
2.Primary Outcome
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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).
Arm/Group Title Reparixin Group Placebo Group
Hide Arm/Group Description:

Continuous iv infusion

Reparixin: 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.

Continuous iv infusion

Placebo: 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.

Overall Number of Participants Analyzed 24 15
Mean (Standard Deviation)
Unit of Measure: ng/mL/min
0.234  (0.243) 0.207  (0.127)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reparixin Group, Placebo Group
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7115
Comments Treatment p value
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least square mean difference
Estimated Value 0.024
Confidence Interval (2-Sided) 99.75%
-0.184 to 0.232
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Insulin-independent Patients at Day 75
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).
Arm/Group Title Reparixin Group Placebo Group
Hide Arm/Group Description:

Continuous iv infusion

Reparixin: 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.

Continuous iv infusion

Placebo: 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.

Overall Number of Participants Analyzed 27 18
Measure Type: Number
Unit of Measure: Percentage of participants
transplant 1 Number Analyzed 27 participants 18 participants
18.5 5.6
transplant 2 Number Analyzed 18 participants 15 participants
27.8 53.3
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reparixin Group, Placebo Group
Comments Analytical statistics are reported for Day 75 after transplant 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1346
Comments Treatment p value
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 0.21
Confidence Interval (2-Sided) 95%
0.03 to 1.63
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Insulin-independent Patients at Day 365
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).
Arm/Group Title Reparixin Group Placebo Group
Hide Arm/Group Description:

Continuous iv infusion

Reparixin: 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.

Continuous iv infusion

Placebo: 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.

Overall Number of Participants Analyzed 25 16
Measure Type: Number
Unit of Measure: percentage of participants
32.0 31.3
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reparixin Group, Placebo Group
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9130
Comments Treatment p value
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
0.17 to 4.93
Estimation Comments [Not Specified]
5.Secondary Outcome
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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (one or two).
Arm/Group Title Reparixin Group Placebo Group
Hide Arm/Group Description:

Continuous iv infusion

Reparixin: 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.

Continuous iv infusion

Placebo: 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.

Overall Number of Participants Analyzed 27 18
Measure Type: Number
Unit of Measure: Percentage of participants
40.0 50.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reparixin Group, Placebo Group
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5467
Comments Treatment p value
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.65
Confidence Interval (2-Sided) 95%
0.16 to 2.66
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Patients Who Did Not Receive a 2nd Islet Infusion
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).
Arm/Group Title Reparixin Group Placebo Group
Hide Arm/Group Description:

Continuous iv infusion

Reparixin: 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.

Continuous iv infusion

Placebo: 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.

Overall Number of Participants Analyzed 27 18
Measure Type: Number
Unit of Measure: percentage of participants
14.8 0.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reparixin Group, Placebo Group
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1383
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
7.Secondary Outcome
Title Cumulative Number of Severe Hypoglycaemic Events in the Efficacy Population 1
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).
Arm/Group Title Reparixin Group Placebo Group
Hide Arm/Group Description:

Continuous iv infusion

Reparixin: 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.

Continuous iv infusion

Placebo: 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.

Overall Number of Participants Analyzed 25 16
Mean (Standard Deviation)
Unit of Measure: number of events
2.88  (8.23) 3.50  (7.65)
8.Secondary Outcome
Title Absolute Change From Baseline in Average Daily Insulin Requirements in Efficacy Population 1
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).
Arm/Group Title Reparixin Group Placebo Group
Hide Arm/Group Description:

Continuous iv infusion

Reparixin: 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.

Continuous iv infusion

Placebo: 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.

Overall Number of Participants Analyzed 27 18
Mean (Standard Deviation)
Unit of Measure: IU/kg/day
transplant 1 Number Analyzed 27 participants 18 participants
-0.231  (0.204) -0.220  (0.203)
transplant 2 Number Analyzed 18 participants 15 participants
-0.389  (0.163) -0.463  (0.168)
last transplant Number Analyzed 25 participants 16 participants
-0.302  (0.167) -0.375  (0.208)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reparixin Group, Placebo Group
Comments This is is the analytic statistics for Day 75 (Transplant 1)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6952
Comments Treatment p value
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least square mean difference
Estimated Value -0.021
Confidence Interval (2-Sided) 95%
-0.130 to 0.088
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Reparixin Group, Placebo Group
Comments This is is the analytic statistics for Day 75 (Transplant 2)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5560
Comments This is a treatment p value
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least square mean difference
Estimated Value 0.028
Confidence Interval (2-Sided) 95%
-0.068 to 0.124
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Reparixin Group, Placebo Group
Comments This is the analytic statics for Day 365 (last Transplant)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2537
Comments Treatment p value
Method ANCOVA
Comments Treatment p value
Method of Estimation Estimation Parameter least square mean difference
Estimated Value 0.056
Confidence Interval (2-Sided) 95%
-0.042 to 0.154
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Percent Change From Baseline in Average Daily Insulin Requirements in Efficacy Population 1
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).
Arm/Group Title Reparixin Group Placebo Group
Hide Arm/Group Description:

Continuous iv infusion

Reparixin: 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.

Continuous iv infusion

Placebo: 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.

Overall Number of Participants Analyzed 27 18
Mean (Standard Deviation)
Unit of Measure: Percentage change
Transplant 1 Number Analyzed 27 participants 18 participants
-42.5  (54.1) -35.0  (35.3)
Transplant 2 Number Analyzed 18 participants 15 participants
-74.0  (28.6) -27.7  (26.3)
Last transplant Number Analyzed 25 participants 16 participants
-59.4  (35.8) -63.7  (33.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reparixin Group, Placebo Group
Comments This is the analytic statics for Day 75 (Transplant 1)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5910
Comments Treatment p value
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least square mean difference
Estimated Value -7.4
Confidence Interval (2-Sided) 95%
-35.2 to 20.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Reparixin Group, Placebo Group
Comments This is the analytic statics for Day 75 (Transplant 2)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5966
Comments Treatment p value
Method ANCOVA
Comments Treatment p value
Method of Estimation Estimation Parameter least square mean difference
Estimated Value 4.2
Confidence Interval (2-Sided) 95%
-11.8 to 20.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Reparixin Group, Placebo Group
Comments This is the analytic statics for Day 365 (last Transplant)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5005
Comments Treatment p value
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least square mean difference
Estimated Value 6.1
Confidence Interval (2-Sided) 95%
-12.1 to 24.4
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Absolute Change in HbA1c % From Pre-transplant Levels in Efficacy Population 1
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).
Arm/Group Title Reparixin Group Placebo Group
Hide Arm/Group Description:

Continuous iv infusion

Reparixin: 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.

Continuous iv infusion

Placebo: 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.

Overall Number of Participants Analyzed 27 18
Mean (Standard Deviation)
Unit of Measure: percent of HbA1c
Transplant 1 Number Analyzed 27 participants 18 participants
-1.58  (0.87) -2.18  (1.23)
Transplant 2 Number Analyzed 18 participants 15 participants
-2.04  (1.10) -2.81  (1.37)
Last Transplant Number Analyzed 27 participants 18 participants
-1.30  (1.14) -1.87  (1.26)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reparixin Group, Placebo Group
Comments This is the analytic statics for Day 75 (Transplant 1)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3253
Comments Treatment p value
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least square mean difference
Estimated Value 0.21
Confidence Interval (2-Sided) 95%
-0.21 to 0.63
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Reparixin Group, Placebo Group
Comments This is the analytic statics for Day 75 (Transplant 2)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6069
Comments Treatment p value
Method least square mean difference
Comments [Not Specified]
Method of Estimation Estimation Parameter least square mean difference
Estimated Value 0.16
Confidence Interval (2-Sided) 95%
-0.46 to 0.78
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Reparixin Group, Placebo Group
Comments This is the analytic statics for Day 365 (last Transplant)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6437
Comments Treatment p value
Method ANCOVA
Comments Treatment p value
Method of Estimation Estimation Parameter Least square mean difference
Estimated Value 0.17
Confidence Interval (2-Sided) 95%
-0.56 to 0.93
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Percent Change in HbA1c % From Pre-transplant Levels in Efficacy Population 1
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).
Arm/Group Title Reparixin Group Placebo Group
Hide Arm/Group Description:

Continuous iv infusion

Reparixin: 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.

Continuous iv infusion

Placebo: 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.

Overall Number of Participants Analyzed 27 18
Mean (Standard Deviation)
Unit of Measure: Percent change of Hb1Ac %
Transplant 1 Number Analyzed 27 participants 18 participants
-18.9  (9.5) -24.0  (10.6)
Transplant 2 Number Analyzed 18 participants 15 participants
-24.4  (11.6) -30.5  (11.7)
Last Transplant Number Analyzed 25 participants 16 participants
-15.7  (13.1) -20.9  (12.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reparixin Group, Placebo Group
Comments This is the analytic statistics for Day 75 (Transplant 1)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4290
Comments Treatment p value
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least square mean difference
Estimated Value 2.0
Confidence Interval (2-Sided) 95%
-3.0 to 6.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Reparixin Group, Placebo Group
Comments This is the analytic statistics for Day 75 (Transplant 2)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7853
Comments Treatment p value
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least square mean difference
Estimated Value 1.0
Confidence Interval (2-Sided) 95%
-6.3 to 8.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Reparixin Group, Placebo Group
Comments This is the analytic statistics for Day 365 (last Transplant)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6583
Comments Treatment p value
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least square mean difference
Estimated Value 1.9
Confidence Interval (2-Sided) 95%
-6.6 to 10.4
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Basal (Fasting) and 0 to 120 Min Time Course of Glucose Derived From the Mixed Meal Tolerance Test (MMTT) in Efficacy Population 1
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).
Arm/Group Title Reparixin Group Placebo Group
Hide Arm/Group Description:

Continuous iv infusion

Reparixin: 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.

Continuous iv infusion

Placebo: 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.

Overall Number of Participants Analyzed 27 18
Mean (Standard Deviation)
Unit of Measure: mg/dL
Basal - day 75 - Transplant 1 Number Analyzed 27 participants 18 participants
120.6  (51.7) 118.9  (40.2)
15 min - day 75 - Transplant 1 Number Analyzed 26 participants 17 participants
146.0  (56.0) 132.5  (27.6)
30 min - day 75 - Transplant 1 Number Analyzed 27 participants 17 participants
191.6  (66.6) 168.1  (50.0)
60 min - day 75 - Transplant 1 Number Analyzed 27 participants 17 participants
236.9  (86.0) 219.1  (65.9)
90 min - day 75 - Transplant 1 Number Analyzed 27 participants 17 participants
254.0  (110.1) 245.0  (84.7)
120 min - day 75 - Transplant 1 Number Analyzed 27 participants 16 participants
264.1  (116.7) 246.0  (84.4)
Basal - day 75 - Transplant 2 Number Analyzed 17 participants 12 participants
103.8  (19.8) 112.8  (18.6)
15 min - day 75 - Transplant 2 Number Analyzed 17 participants 12 participants
130.0  (22.3) 134.8  (26.8)
30 min - day 75 - Transplant 2 Number Analyzed 17 participants 12 participants
166.7  (33.6) 157.8  (32.6)
60 min - day 75 - Transplant 2 Number Analyzed 17 participants 12 participants
189.1  (57.9) 172.0  (70.9)
90 min - day 75 - Transplant 2 Number Analyzed 17 participants 12 participants
191.8  (72.8) 175.1  (99.7)
120 min - day 75 - Transplant 2 Number Analyzed 17 participants 12 participants
188.0  (88.1) 171.7  (104.8)
Basal - day 365 - Last transplant Number Analyzed 24 participants 15 participants
112.2  (37.6) 125.1  (64.5)
15 min - day 365 - Last transplant Number Analyzed 24 participants 15 participants
139.5  (43.1) 146.7  (68.9)
30 min - day 365 - Last transplant Number Analyzed 24 participants 15 participants
180.1  (53.9) 182.7  (80.2)
60 min - day 365 - Last transplant Number Analyzed 24 participants 15 participants
221.2  (81.2) 213.6  (106.2)
90 min - day 365 - Last transplant Number Analyzed 24 participants 15 participants
235.7  (112.6) 222.0  (122.6)
120 min - day 365 - Transplant 2 Number Analyzed 23 participants 14 participants
239.9  (127.6) 205.5  (104.3)
13.Secondary Outcome
Title Basal (Fasting) and 0 to 120 Min Time Course of C-peptide (Non-normalized) Derived From the MMTT in Efficacy Population 1
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).
Arm/Group Title Reparixin Group Placebo Group
Hide Arm/Group Description:

Continuous iv infusion

Reparixin: 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.

Continuous iv infusion

Placebo: 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.

Overall Number of Participants Analyzed 27 18
Mean (Standard Deviation)
Unit of Measure: ng/mL
Basal - day 75 - Transplant 1 Number Analyzed 27 participants 18 participants
0.50  (0.46) 0.51  (0.44)
15 min - day 75 - Transplant 1 Number Analyzed 26 participants 18 participants
0.71  (0.77) 0.67  (0.71)
30 min - day 75 - Transplant 1 Number Analyzed 26 participants 18 participants
1.18  (1.32) 0.89  (0.90)
60 min - day 75 - Transplant 1 Number Analyzed 27 participants 18 participants
1.66  (1.80) 1.46  (1.43)
90 min - day 75 - Transplant 1 Number Analyzed 27 participants 18 participants
1.81  (1.64) 1.80  (1.57)
120 min - day 75 - Transplant 1 Number Analyzed 27 participants 17 participants
1.72  (1.34) 2.04  (1.64)
Basal - day 75 - Transplant 2 Number Analyzed 17 participants 12 participants
0.93  (0.69) 1.27  (0.50)
15 min - day 75 - Transplant 2 Number Analyzed 17 participants 12 participants
1.42  (1.36) 1.73  (0.78)
30 min - day 75 - Transplant 2 Number Analyzed 17 participants 12 participants
2.13  (1.90) 2.55  (1.19)
60 min - day 75 - Transplant 2 Number Analyzed 17 participants 12 participants
2.98  (2.15) 3.65  (2.09)
90 min - day 75 - Transplant 2 Number Analyzed 17 participants 12 participants
3.30  (2.15) 3.56  (1.96)
120 min - day 75 - Transplant 2 Number Analyzed 17 participants 12 participants
3.33  (1.98) 2.90  (1.28)
Basal - day 365 - Last transplant Number Analyzed 24 participants 15 participants
0.76  (0.65) 1.14  (0.62)
15 min - day 365 - Last transplant Number Analyzed 23 participants 15 participants
1.06  (1.02) 1.32  (0.90)
30 min - day 365 - Last transplant Number Analyzed 24 participants 15 participants
1.65  (1.66) 2.17  (1.50)
60 min - day 365 - Last transplant Number Analyzed 24 participants 15 participants
2.37  (2.38) 2.88  (181)
90 min - day 365 - Last transplant Number Analyzed 24 participants 15 participants
2.47  (2.27) 3.13  (1.84)
120 min - day 365 - Transplant 2 Number Analyzed 24 participants 14 participants
2.11  (1.74) 3.12  (1.68)
14.Secondary Outcome
Title Basal (Fasting) and 0 to 120 Min Time Course of Insulin Derived From the MMTT in Efficacy Population 1
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).
Arm/Group Title Reparixin Group Placebo Group
Hide Arm/Group Description:

Continuous iv infusion

Reparixin: 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.

Continuous iv infusion

Placebo: 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.

Overall Number of Participants Analyzed 27 18
Mean (Standard Deviation)
Unit of Measure: µU/mL
Basal - day 75 - Transplant 1 Number Analyzed 27 participants 18 participants
16.5  (43.6) 15.2  (39.8)
15 min - day 75 - Transplant 1 Number Analyzed 23 participants 17 participants
13.5  (16.6) 11.8  (13.2)
30 min - day 75 - Transplant 1 Number Analyzed 24 participants 17 participants
21.0  (27.7) 15.8  (16.9)
60 min - day 75 - Transplant 1 Number Analyzed 25 participants 17 participants
25.6  (32.9) 23.0  (24.4)
90 min - day 75 - Transplant 1 Number Analyzed 25 participants 17 participants
23.9  (27.4) 22.3  (18.8)
120 min - day 75 - Transplant 1 Number Analyzed 25 participants 16 participants
21.3  (28.2) 23.1  (18.1)
Basal - day 75 - Transplant 2 Number Analyzed 16 participants 12 participants
8.4  (10.3) 9.0  (3.8)
15 min - day 75 - Transplant 2 Number Analyzed 17 participants 11 participants
16.0  (16.0) 17.5  (12.1)
30 min - day 75 - Transplant 2 Number Analyzed 17 participants 11 participants
28.4  (30.0) 31.1  (17.8)
60 min - day 75 - Transplant 2 Number Analyzed 17 participants 11 participants
33.7  (23.4) 37.8  (20.4)
90 min - day 75 - Transplant 2 Number Analyzed 16 participants 11 participants
36.3  (23.6) 31.2  (20.6)
120 min - day 75 - Transplant 2 Number Analyzed 17 participants 11 participants
29.7  (19.2) 25.3  (10.4)
Basal - day 365 - Last transplant Number Analyzed 24 participants 15 participants
7.5  (7.6) 6.2  (4.0)
15 min - day 365 - Last transplant Number Analyzed 23 participants 15 participants
13.8  (17.0) 10.8  (9.0)
30 min - day 365 - Last transplant Number Analyzed 24 participants 15 participants
19.4  (19.2) 20.7  (13.1)
60 min - day 365 - Last transplant Number Analyzed 24 participants 15 participants
28.5  (30.1) 25.6  (14.3)
90 min - day 365 - Last transplant Number Analyzed 24 participants 15 participants
25.8  (23.5) 26.1  (17.8)
120 min - day 365 - Transplant 2 Number Analyzed 24 participants 14 participants
19.9  (18.4) 27.1  (11.8)
15.Secondary Outcome
Title β-cell Function as Assessed by β-score in Efficacy Population 1
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).
Arm/Group Title Reparixin Group Placebo Group
Hide Arm/Group Description:

Continuous iv infusion

Reparixin: 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.

Continuous iv infusion

Placebo: 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.

Overall Number of Participants Analyzed 27 18
Mean (Standard Deviation)
Unit of Measure: score on a scale
day 75 - Transplant 1 Number Analyzed 27 participants 18 participants
4.19  (2.37) 4.06  (2.29)
day 75 - Transplant 2 Number Analyzed 17 participants 12 participants
5.53  (1.42) 5.67  (2.06)
day 365 - Last transplant Number Analyzed 24 participants 15 participants
4.63  (2.50) 5.13  (2.42)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reparixin Group, Placebo Group
Comments This is the analytic statistics for Day 75 (Transplant 1)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9949
Comments Treatment p value
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square mean difference
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
-1.28 to 1.28
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Reparixin Group, Placebo Group
Comments This is the analytic statistics for Day 75 (Transplant 2)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8753
Comments Treatment p value
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square mean difference
Estimated Value 0.10
Confidence Interval (2-Sided) 95%
-1.18 to 1.38
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Reparixin Group, Placebo Group
Comments This is the analytic statistics for Day 365 (last Transplant)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3955
Comments Treatment p value
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square mean difference
Estimated Value -0.59
Confidence Interval (2-Sided) 95%
-1.97 to 0.80
Estimation Comments [Not Specified]
16.Secondary Outcome
Title β-cell Function as Assessed by Transplant Estimated Function (TEF) in Efficacy Population 1
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).
Arm/Group Title Reparixin Group Placebo Group
Hide Arm/Group Description:

Continuous iv infusion

Reparixin: 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.

Continuous iv infusion

Placebo: 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.

Overall Number of Participants Analyzed 27 18
Mean (Standard Deviation)
Unit of Measure: U/kg/24 h
day 75 - Transplant 1 Number Analyzed 27 participants 18 participants
0.523  (0.260) 0.621  (0.332)
day 75 - Transplant 2 Number Analyzed 18 participants 15 participants
0.764  (0.240) 0.981  (0.275)
day 365 - Last transplant Number Analyzed 25 participants 16 participants
0.539  (0.320) 0.719  (0.359)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reparixin Group, Placebo Group
Comments This is the analytic statistics for Day 75 (Transplant 1)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2444
Comments Treatment p value
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square mean difference
Estimated Value -0.105
Confidence Interval (2-Sided) 95%
-0.286 to 0.075
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Reparixin Group, Placebo Group
Comments This is the analytic statistics for Day 75 (Transplant 2)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0328
Comments Treatment p value
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square mean difference
Estimated Value -0.218
Confidence Interval (2-Sided) 95%
-0.417 to -0.019
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Reparixin Group, Placebo Group
Comments This is the analytic statistics for Day 365 (last Transplant)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1059
Comments This is the analytic statistics for Day 75 (Transplant 2)
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square mean difference
Estimated Value -0.177
Confidence Interval (2-Sided) 95%
-0.393 to 0.039
Estimation Comments [Not Specified]
17.Other Pre-specified Outcome
Title Frequency of Patients Positive/Negative for Autoantibodies Against Glutamic Acid Decarboxylase (GAD) in Efficacy Population 1
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).
Arm/Group Title Reparixin Group Placebo Group
Hide Arm/Group Description:

Continuous iv infusion

Reparixin: 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.

Continuous iv infusion

Placebo: 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.

Overall Number of Participants Analyzed 27 18
Measure Type: Number
Unit of Measure: Percentage of participants
pre-transplant 1 - positive Number Analyzed 27 participants 17 participants
48.1 52.9
pre-transplant 1 - negative Number Analyzed 27 participants 17 participants
51.9 47.1
day 75 - Transplant 1 - positive Number Analyzed 26 participants 17 participants
69.2 64.7
day 75 - Transplant 1 - negative Number Analyzed 26 participants 17 participants
30.8 35.3
pre-transplant 2 - positive Number Analyzed 18 participants 16 participants
66.7 62.5
pre-transplant 2 - negative Number Analyzed 18 participants 16 participants
33.3 37.5
day 75 - Transplant 2 - positive Number Analyzed 18 participants 15 participants
66.7 53.3
day 75 - Transplant 2 - negative Number Analyzed 18 participants 15 participants
33.3 46.7
day 365 - Last transplant - positive Number Analyzed 25 participants 16 participants
56.0 50.0
day 365 - Last transplant - negative Number Analyzed 25 participants 16 participants
44.0 50.0
18.Other Pre-specified Outcome
Title Frequency of Patients Positive/Negative for Autoantibodies Against Islet Antigen-2 (IA-2) in Efficacy Population 1
Hide 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,
Hide Outcome Measure Data
Hide Analysis Population Description
The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).
Arm/Group Title Reparixin Group Placebo Group
Hide Arm/Group Description:

Continuous iv infusion

Reparixin: 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.

Continuous iv infusion

Placebo: 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.

Overall Number of Participants Analyzed 27 18
Measure Type: Number
Unit of Measure: Percentage of participants
pre-transplant 1 - positive Number Analyzed 27 participants 14 participants
22.2 14.3
pre-transplant 1 - negative Number Analyzed 27 participants 14 participants
77.8 85.7
day 75 - Transplant 1 - positive Number Analyzed 25 participants 15 participants
28.0 20.0
day 75 - Transplant 1 - negative Number Analyzed 25 participants 15 participants
72.0 80.0
pre-transplant 2 - positive Number Analyzed 18 participants 15 participants
22.2 13.3
pre-transplant 2 - negative Number Analyzed 18 participants 15 participants
77.8 86.7
day 75 - Transplant 2 - positive Number Analyzed 18 participants 14 participants
27.8 14.3
day 75 - Transplant 2 - negative Number Analyzed 18 participants 14 participants
72.2 85.7
day 365 - Last transplant - positive Number Analyzed 25 participants 15 participants
20.0 20.0
day 365 - Last transplant - negative Number Analyzed 25 participants 15 participants
80.0 80.0
19.Other Pre-specified Outcome
Title Frequency of Patients Positive/Negative for Autoantibodies Against Class I Human Leucocyte Antigen (HLA) in Efficacy Population 1
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).
Arm/Group Title Reparixin Group Placebo Group
Hide Arm/Group Description:

Continuous iv infusion

Reparixin: 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.

Continuous iv infusion

Placebo: 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.

Overall Number of Participants Analyzed 27 18
Measure Type: Number
Unit of Measure: Percentage of participants
pre-transplant 1 - positive 15.4 27.8
pre-transplant 1 - negative 84.6 72.2
day 75 - Transplant 1 - positive 20.0 23.5
day 75 - Transplant 1 - negative 80.0 76.5
pre-transplant 2 - positive 29.4 31.3
pre-transplant 2 - negative 70.6 68.8
day 75 - Transplant 2 - positive 33.3 26.7
day 75 - Transplant 2 - negative 66.7 73.3
day 365 - Last transplant - positive 28.0 26.7
day 365 - Last transplant - negative 72.0 73.3
20.Other Pre-specified Outcome
Title Frequency of Patients Positive/Negative for Autoantibodies Against Class II Human Leucocyte Antigen (HLA) in Efficacy Population 1
Hide 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,
Hide Outcome Measure Data
Hide Analysis Population Description
The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).
Arm/Group Title Reparixin Group Placebo Group
Hide Arm/Group Description:

Continuous iv infusion

Reparixin: 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.

Continuous iv infusion

Placebo: 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.

Overall Number of Participants Analyzed 27 18
Measure Type: Number
Unit of Measure: Percentage of participants
pre-transplant 1 - positive 7.7 5.6
pre-transplant 1 - negative 92.3 94.4
day 75 - Transplant 1 - positive 16.0 12.5
day 75 - Transplant 1 - negative 84.0 87.5
pre-transplant 2 - positive 5.9 6.3
pre-transplant 2 - negative 94.1 93.8
day 75 - Transplant 2 - positive 16.7 6.7
day 75 - Transplant 2 - negative 83.3 93.3
day 365 - Last transplant - positive 20.0 20.0
day 365 - Last transplant - negative 80.0 80.0
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Reparixin Group Placebo Group
Hide Arm/Group Description

Continuous iv infusion

Reparixin: 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.

Continuous iv infusion

Placebo: 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.

All-Cause Mortality
Reparixin Group Placebo Group
Affected / at Risk (%) Affected / at Risk (%)
Total   0/29 (0.00%)      0/19 (0.00%)    
Hide Serious Adverse Events
Reparixin Group Placebo Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   17/29 (58.62%)      12/19 (63.16%)    
Blood and lymphatic system disorders     
Anaemia  1  3/29 (10.34%)  4 1/19 (5.26%)  2
Leukopenia  1  1/29 (3.45%)  1 1/19 (5.26%)  1
Neutropenia  1  1/29 (3.45%)  1 1/19 (5.26%)  1
Gastrointestinal disorders     
Abdominal pain  1  2/29 (6.90%)  2 1/19 (5.26%)  1
Abdominal pain upper  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Diarrhoea  1  2/29 (6.90%)  2 0/19 (0.00%)  0
Intra-abdominal haemmorrhage  1  2/29 (6.90%)  2 2/19 (10.53%)  2
Nausea  1  1/29 (3.45%)  1 1/19 (5.26%)  3
Vomiting  1  2/29 (6.90%)  2 1/19 (5.26%)  2
Peritoneal haemorrhage  1  2/29 (6.90%)  2 1/19 (5.26%)  1
General disorders     
Implant site haemorrhage  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Multiple organ dysfunction syndrome  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Oedema peripheral  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Puncture site haemorrhage  1  0/29 (0.00%)  0 1/19 (5.26%)  1
Pyrexia  1  0/29 (0.00%)  0 1/19 (5.26%)  1
Hepatobiliary disorders     
Hepatic haematoma  1  0/29 (0.00%)  0 1/19 (5.26%)  1
Immune system disorders     
Alloimmunisation  1  2/29 (6.90%)  2 0/19 (0.00%)  0
Drug Hypersensititity  1  0/29 (0.00%)  0 1/19 (5.26%)  1
Transplant rejection  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Infections and infestations     
Localised infection  1  0/29 (0.00%)  0 1/19 (5.26%)  1
Pneumonia  1  0/29 (0.00%)  0 1/19 (5.26%)  1
Sepsis  1  1/29 (3.45%)  1 1/19 (5.26%)  1
Streptococcal sepsis  1  0/29 (0.00%)  0 1/19 (5.26%)  1
Urinary Tract Infection  1  0/29 (0.00%)  0 1/19 (5.26%)  1
Injury, poisoning and procedural complications     
Cervical vertebral fracture  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Complications of transplant surgery  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Upper limb fracture  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Investigations     
HLA marker study positive  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Hepatic enzyme increased  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Panel-reactive antibody increased  1  0/29 (0.00%)  0 1/19 (5.26%)  1
Metabolism and nutrition disorders     
Dehydration  1  0/29 (0.00%)  0 1/19 (5.26%)  3
Hypoglycemia  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Ketosis  1  0/29 (0.00%)  0 1/19 (5.26%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Adenocarcinoma  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Nervous system disorders     
Diabetic neuropathy  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Generalised tonic-clonic seizure  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Headache  1  2/29 (6.90%)  2 0/19 (0.00%)  0
Psychiatric disorders     
Acute psychosis  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Renal and urinary disorders     
Urinary retantion  1  0/29 (0.00%)  0 1/19 (5.26%)  1
Respiratory, thoracic and mediastinal disorders     
Oropharyngeal ache  1  0/29 (0.00%)  0 1/19 (5.26%)  1
Pulmonary embolism  1  0/29 (0.00%)  0 1/19 (5.26%)  1
Vascular disorders     
Haemorrhage  1  1/29 (3.45%)  1 0/19 (0.00%)  0
1
Term from vocabulary, MedDRA 19.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Reparixin Group Placebo Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   29/29 (100.00%)      18/19 (94.74%)    
Blood and lymphatic system disorders     
Anaemia  1  6/29 (20.69%)  6 2/19 (10.53%)  4
Leukopenia  1  0/29 (0.00%)  0 1/19 (5.26%)  1
Neutropenia  1  1/29 (3.45%)  1 2/19 (10.53%)  2
Cardiac disorders     
Angina pectoris  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Bradycardia  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Tachycardia  1  2/29 (6.90%)  3 1/19 (5.26%)  1
Eye disorders     
Vision blurred  1  0/29 (0.00%)  0 1/19 (5.26%)  1
Vitreous floaters  1  0/29 (0.00%)  0 1/19 (5.26%)  1
Gastrointestinal disorders     
Abdominal pain  1  7/29 (24.14%)  7 7/19 (36.84%)  9
Abdominal pain upper  1  1/29 (3.45%)  1 2/19 (10.53%)  2
Constipation  1  3/29 (10.34%)  3 0/19 (0.00%)  0
Diarrhoea  1  7/29 (24.14%)  8 2/19 (10.53%)  3
Lip oedema  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Lip swelling  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Nausea  1  13/29 (44.83%)  17 12/19 (63.16%)  15
Stomatitis  1  2/29 (6.90%)  2 1/19 (5.26%)  1
Vomiting  1  7/29 (24.14%)  7 6/19 (31.58%)  6
General disorders     
Catheter site haemorrhage  1  1/29 (3.45%)  1 1/19 (5.26%)  1
Catheter site pain  1  3/29 (10.34%)  4 2/19 (10.53%)  2
Chest discomfort  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Chills  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Fatigue  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Generalised oedema  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Implant site haemorrhage  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Malaise  1  4/29 (13.79%)  5 1/19 (5.26%)  1
Peripheral swelling  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Pyrexia  1  3/29 (10.34%)  4 6/19 (31.58%)  6
Vessel puncture site erythema  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Hepatobiliary disorders     
Hepatic haemorrhage  1  1/29 (3.45%)  2 0/19 (0.00%)  0
Infections and infestations     
Coccidioidomycosis  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Urinary tract infection  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Injury, poisoning and procedural complications     
Contusion  1  0/29 (0.00%)  0 1/19 (5.26%)  1
Fall  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Head injury  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Incision site pain  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Post procedural heamatoma  1  0/29 (0.00%)  0 1/19 (5.26%)  1
Procedural pain  1  3/29 (10.34%)  3 1/19 (5.26%)  2
Wound Dehiscence  1  0/29 (0.00%)  0 1/19 (5.26%)  1
Investigations     
Aspartate aminotransferase increased  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Blood creatinine increased  1  3/29 (10.34%)  3 0/19 (0.00%)  0
Blood magnesium decreased  1  0/29 (0.00%)  0 1/19 (5.26%)  1
Blood potassium decreased  1  0/29 (0.00%)  0 1/19 (5.26%)  1
Blood pressure decreased  1  0/29 (0.00%)  0 1/19 (5.26%)  1
C-reactive protein increased  1  1/29 (3.45%)  1 1/19 (5.26%)  1
Heart rate increased  1  0/29 (0.00%)  0 1/19 (5.26%)  1
Hepatic enzyme increased  1  0/29 (0.00%)  0 2/19 (10.53%)  2
Liver function test increased  1  0/29 (0.00%)  0 1/19 (5.26%)  1
Portal vein presssure increased  1  2/29 (6.90%)  2 1/19 (5.26%)  1
Weight increased  1  0/29 (0.00%)  0 2/19 (10.53%)  2
Metabolism and nutrition disorders     
Decreased appetite  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Fluid retention  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Hyperkalaemia  1  3/29 (10.34%)  5 0/19 (0.00%)  0
Hypervolaemia  1  0/29 (0.00%)  0 1/19 (5.26%)  1
Hypoglycaemia  1  6/29 (20.69%)  6 3/19 (15.79%)  5
Hypokalaemia  1  0/29 (0.00%)  0 1/19 (5.26%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Back pain  1  2/29 (6.90%)  3 2/19 (10.53%)  3
joint swelling  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Muscular weakness  1  0/29 (0.00%)  0 1/19 (5.26%)  1
Musculoskeletal pain  1  3/29 (10.34%)  3 1/19 (5.26%)  1
Neck pain  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Pain in extremity  1  1/29 (3.45%)  1 1/19 (5.26%)  1
Nervous system disorders     
Dizziness  1  0/29 (0.00%)  0 1/19 (5.26%)  1
Dysgeusia  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Headache  1  8/29 (27.59%)  11 7/19 (36.84%)  9
Migrane  1  1/29 (3.45%)  1 2/19 (10.53%)  2
Syncope  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Tremor  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Psychiatric disorders     
Anxiety  1  1/29 (3.45%)  1 3/19 (15.79%)  4
Emotional distress  1  0/29 (0.00%)  0 1/19 (5.26%)  1
Insomnia  1  1/29 (3.45%)  2 2/19 (10.53%)  2
Renal and urinary disorders     
Urinary retention  1  0/29 (0.00%)  0 1/19 (5.26%)  1
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  0/29 (0.00%)  0 1/19 (5.26%)  1
Epistaxis  1  2/29 (6.90%)  2 1/19 (5.26%)  1
Nasal congestion  1  2/29 (6.90%)  2 0/19 (0.00%)  0
Rhinorrhoea  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Upper-airway cough syndrome  1  1/29 (3.45%)  1 1/19 (5.26%)  1
Skin and subcutaneous tissue disorders     
Acne  1  1/29 (3.45%)  1 1/19 (5.26%)  1
Erythema  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Hyperhidrosis  1  1/29 (3.45%)  1 0/19 (0.00%)  0
Pruritus  1  2/29 (6.90%)  2 2/19 (10.53%)  2
Rash  1  0/29 (0.00%)  0 1/19 (5.26%)  1
Skin esfoliation  1  0/29 (0.00%)  0 1/19 (5.26%)  1
Hypertension  1  3/29 (10.34%)  4 0/19 (0.00%)  0
Vascular disorders     
Hot flush  1  1/29 (3.45%)  1 1/19 (5.26%)  1
Hypotension  1  2/29 (6.90%)  2 0/19 (0.00%)  0
1
Term from vocabulary, MedDRA 19.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Andrea Vergani, MD
Organization: Dompé farmaceutici
Phone: +39 02 583831
EMail: info@dompe.it
Layout table for additonal information
Responsible Party: Dompé Farmaceutici S.p.A
ClinicalTrials.gov Identifier: NCT01817959    
Other Study ID Numbers: REP0211
2011-006201-10 ( EudraCT Number )
First Submitted: March 7, 2013
First Posted: March 26, 2013
Results First Submitted: December 2, 2019
Results First Posted: December 18, 2019
Last Update Posted: February 25, 2021