Islet Transplantation in Diabetes Mellitus Type 1Phase 3REP0211NCT01817959
Study to Assess Efficacy & Safety of Reparixin in Pancreatic Islet Transplantation
A Phase 3 study testing Reparixin in people with Islet Transplantation in Diabetes Mellitus Type 1, run by Dompé Farmaceutici S.p.A at 9 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Islet Transplantation in Diabetes Mellitus Type 1
- What is being tested?
- Reparixin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 51 participants
- Where
- 9 sitesin 5 countries
- Study dates
- Oct 2012to Dec 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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prior to any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
Who cannot join
- 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]).
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- 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.
Trial locations and contacts
9 sites in 5 countries.
9 sites in 5 countries
Sweden4 sites
Transplant Institute - Sahlgrenska University Hospital
Gothenburg, 41345
Department of Nephrology and Transplantation; Skane University Hospital
Malmö, 20502
Department of Transplantation Surgery; The Karolinska University Hospital
Stockholm, 14186
Division for Transplantation and Liver Surgery; Department of Surgery; Uppsala University Hospital
Uppsala, 75185
Italy2 sites
Dipartimento di Medicina Interna e Specialistica; IRCCS Ospedale San Raffaele
Milan, 20132
S.S.D. Diabetologia, Azienda Ospedaliera Ospedale Niguarda Ca' Granda, Piazza Ospedale Maggiore 3
Milan, 20162
United States1 site
The University of Chicago Medical Center, Department of Surgery, Division of Abdominal Organ Transplantation
Chicago, Illinois, 60637
Czechia1 site
Institute for Clinical and Experimental Medicine (IKEM), Diabetes Centre; Department of Diabetes.
Prague, 14021
United Kingdom1 site
Institute of Transplantation, Newcastle upon Tyne Hospitals - NHS Foundation Trust, Freeman Hospital
Newcastle upon Tyne, NE7 7DN
About this study
Official title: A Phase 3, Multicenter, Randomized, Double-blind, Parallel Assignment Study to Assess the Efficacy and Safety of Reparixin in Pancreatic Islet Transplantation
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.
Read the 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.
- Being tested
- Reparixin, Placebo
- Keywords
- Pancreatic islet transplantation, Diabetes Mellitus Type 1, Islet transplantation graft survival & function
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ReparixinDrug
Also called REP
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Reparixin group | Experimental | Continuous iv infusion Receives: Drug: Reparixin |
| Placebo group | Placebo comparator | Continuous iv infusion Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Basal, -15' prior to meal, 15', 30', 60', 90', 120' following meal, Day 75±5 after the 1st islet infusion
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.
Measured: Basal, -15' prior to meal, 15', 30', 60', 90', 120' following meal, Day 365±14 after the last islet infusion
Secondary outcomes (14)
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).
Measured: Day 75±5 after the 1st and 2nd islet infusion
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).
Measured: Day 365±14 after last islet infusion
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.
Measured: HbA1c at Day 365±14 after the last islet infusion; severe hypoglycaemic events from Day 75 to Day 365 after the last islet infusion
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.
Measured: Day 365±14 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.
Measured: Day 365±14 after the last islet infusion
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.
Measured: Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion
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.
Measured: Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion
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.
Measured: Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion
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.
Measured: Day 75±5 after the 1st and 2nd islet infusion and day 365+14 after last islet infusion
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.
Measured: Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion
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.
Measured: Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion
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.
Measured: Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion
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
Measured: Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion
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)
Measured: Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2013 (estimated)
- Study startOct 2012
- Primary completionDec 2016
- Study completionDec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Islet Transplantation in Diabetes Mellitus Type 1Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dompé Farmaceutici S.p.A
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Lorenzo PIEMONTI, MD, Principal investigator, Dipartimento di Medicina Interna e Specialistica; IRCCS Ospedale San RaffaeleTorbjörn LUNDGREN, MD, PhD, Principal investigator, Department of Transplantation Surgery; The Karolinska University HospitalGunnar TUFVESON, Professor, Principal investigator, Department of Surgery; Uppsala University HospitalEhab RAFAEL, MD, PhD, Principal investigator, Department of Nephrology and Transplantation; Skane University HospitalJames SHAW, Professor, Principal investigator, Institute of Transplantation, Newcastle upon Tyne Hospitals - Freeman HospitalFrantisek SAUDEK, MD, DrSc, Principal investigator, Institute for Clinical and Experimental Medicine (IKEM), Department of Diabetes.Piotr WITKOWSKI, MD, PhD, Principal investigator, The University of Chicago Medical Center, Department of SurgeryFederico BERTUZZI, MD, Principal investigator, S.S.D. Diabetologia, Azienda Ospedaliera Ospedale Niguarda Ca' Granda, Milano
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01817959
- Sponsor's protocol ID
- REP0211
- Other IDs
- 2011-006201-10
- Acronym
- REP0211
- Status last verified
- Sep 2021
- First submitted
- 7 Mar 2013
- Last updated
- 3 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Ajmal N, Bogart MC, Khan P, Max-Harry IM, Healy AM, Nunemaker CS. Identifying Promising Immunomodulators for Type 1 Diabetes (T1D) and Islet Transplantation. J Diabetes Res. 2024 Dec 20;2024:5151171. doi: 10.1155/jdr/5151171. eCollection 2024.
PubMed 39735417Bachul 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.
PubMed 33908301Maffi 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.
PubMed 32019854
Study at a glance
From the registry record, last updated by the sponsor on 3 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Multicenter, Randomized, Double-blind, Parallel Assignment Study to Assess the Efficacy and Safety of Reparixin in Pancreatic Islet Transplantation
- ClinicalTrials.gov ID
- NCT01817959
- Acronym / sponsor ID
- REP0211 / REP0211
- Keywords
- Pancreatic islet transplantation, Diabetes Mellitus Type 1, Islet transplantation graft survival & function
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Dompé Farmaceutici S.p.AIndustry (pharma, biotech, devices)
- Study start
- Oct 2012
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 26 Mar 2013 (estimated)
- Results
- Posted 18 Dec 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Reparixin group | Experimental | Drug: ReparixinContinuous iv infusion |
| Placebo group | Placebo comparator | Drug: PlaceboContinuous iv infusion |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (14 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ReparixinAlso: REPContinuous 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. | Drug | Reparixin group |
| PlaceboContinuous 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. | Drug | Placebo group |
Primary outcome
Area Under the Curve (AUC) for the Serum C-peptide Level During the First 2 Hours of an MMTT (Mixed Meal Tolerance Test), Normalized by the Number of Islet Equivalent (IEQ)/kg
Time frame: Basal, -15' prior to meal, 15', 30', 60', 90', 120' following meal, Day 75±5 after the 1st islet infusion
The MMTT was to be performed ideally after an overnight fast. The test was to be initiated before 10 a.m. The Boost Original complete nutritional drink (Nestlé Nutrition) was used for the MMTT. Subjects were given 6 mL/kg of Boost preparation up to a maximum of 360 mL, to be drunk within 5 min. Blood samples for the C-peptide assay (the primary assessment) were withdrawn in fasting condition (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
Time frame: Basal, -15' prior to meal, 15', 30', 60', 90', 120' following meal, Day 365±14 after the last islet infusion
The MMTT was to be performed ideally after an overnight fast. The test was to be initiated before 10 a.m. The Boost Original complete nutritional drink (Nestlé Nutrition) was used for the MMTT. Subjects were given 6 mL/kg of Boost preparation up to a maximum of 360 mL, to be drunk within 5 min. Blood samples for the C-peptide assay (the primary assessment) were withdrawn in fasting condition (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.
14 secondary outcomes
Percentage of Insulin-independent Patients at Day 75
Time frame: Day 75±5 after the 1st and 2nd islet infusion
Percentage of Insulin-independent Patients at Day 365
Time frame: Day 365±14 after last islet infusion
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
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
Percentage of Patients Who Did Not Receive a 2nd Islet Infusion
Time frame: Day 365±14 after the 1st islet infusion
Cumulative Number of Severe Hypoglycaemic Events in the Efficacy Population 1
Time frame: Day 365±14 after the last islet infusion
Absolute Change From Baseline in Average Daily Insulin Requirements in Efficacy Population 1
Time frame: Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion
Percent Change From Baseline in Average Daily Insulin Requirements in Efficacy Population 1
Time frame: Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion
Absolute Change in HbA1c % From Pre-transplant Levels in Efficacy Population 1
Time frame: Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion
Percent Change in HbA1c % From Pre-transplant Levels in Efficacy Population 1
Time frame: Day 75±5 after the 1st and 2nd islet infusion and day 365+14 after last islet infusion
Basal (Fasting) and 0 to 120 Min Time Course of Glucose Derived From the Mixed Meal Tolerance Test (MMTT) in Efficacy Population 1
Time frame: Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion
Basal (Fasting) and 0 to 120 Min Time Course of C-peptide (Non-normalized) Derived From the MMTT in Efficacy Population 1
Time frame: Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion
Basal (Fasting) and 0 to 120 Min Time Course of Insulin Derived From the MMTT in Efficacy Population 1
Time frame: Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion
β-cell Function as Assessed by β-score in Efficacy Population 1
Time frame: Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion
β-cell Function as Assessed by Transplant Estimated Function (TEF) in Efficacy Population 1
Time frame: Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39735417Ajmal N, Bogart MC, Khan P, Max-Harry IM, Healy AM, Nunemaker CS. Identifying Promising Immunomodulators for Type 1 Diabetes (T1D) and Islet Transplantation. J Diabetes Res. 2024 Dec 20;2024:5151171. doi: 10.1155/jdr/5151171. eCollection 2024.
- Derived from this study: PubMed 33908301Bachul 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.
- Derived from this study: PubMed 32019854Maffi 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lorenzo PIEMONTI, MD principal investigator
Dipartimento di Medicina Interna e Specialistica; IRCCS Ospedale San Raffaele
Torbjörn LUNDGREN, MD, PhD principal investigator
Department of Transplantation Surgery; The Karolinska University Hospital
Gunnar TUFVESON, Professor principal investigator
Department of Surgery; Uppsala University Hospital
9 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Reparixin in people with Islet Transplantation in Diabetes Mellitus Type 1, run by Dompé Farmaceutici S.p.A at 9 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Sweden, Italy, United States, Czechia, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area Under the Curve (AUC) for the Serum C-peptide Level During the First 2 Hours of an MMTT (Mixed Meal Tolerance Test), Normalized by the Number of Islet Equivalent (IEQ)/kg (time frame: Basal, -15' prior to meal, 15', 30', 60', 90', 120' following meal, Day 75±5 after the 1st islet infusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01817959, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jan 2024.