E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
intrahepatic islet transplantation |
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E.1.1.1 | Medical condition in easily understood language |
intrahepatic islet transplantation |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10058846 |
E.1.2 | Term | Pancreas islet cell transplant |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objective of this clinical trial is to evaluate whether CXCL8 inhibition with reparixin leads to improved functional and clinical outcome in intrahepatic islet transplantation patients.
The safety of reparixin in the specific clinical setting will be also evaluated. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Ages 18-65 years, inclusive.
2. Patients eligible for pancreatic islet transplantation program based on local accepted practice and guidelines. This includes at least:
- clinical history compatible with T1D with insulin-dependence for >= 5 years;
- undetectable stimulated (arginine or MMTT) C-peptide levels (<0.3 ng/mL) evidenced at any time before transplant.
Sites will comply with any additional or more stringent criteria locally accepted, as
per centre practice.
3. Patients with adequate renal reserve as per calculated creatinine clearance (CLcr) >= 60 mL/min according to the Cockcroft-Gault formula (1976).
4. Planned intrahepatic islet transplantation alone from a non-living donor with brain death.
5. Planned first infusion of 4000 to 7000 islet equivalent (IEQ)/kg body weight.
6. Patients willing and able to comply with the protocol procedures for the duration of the study, including scheduled follow-up visits and examinations.
7. Patients given written informed consent, prior to any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care. |
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E.4 | Principal exclusion criteria |
1. Recipients of any previous transplant, except from recipients of a previous pancreatic islet transplantation that has failed, are off immunosuppression since at least 1 year and have negative anti-HLA.
2. Recipients of islet from a non-heart beating donor.
3. A body mass index >30 kg/m2 or patient weight <= 45 kg
4. Pre-transplant average daily insulin requirement >1 IU/kg/day
5. Pre-transplant HbA1c >10%.
6. Patients with hepatic dysfunction as defined by increased ALT/AST > 3 x upper limit of normal (ULN) and increased total bilirubin > 3mg/dL [>51.3 μmol/L]).
7. Patients who receive treatment for a medical condition requiring chronic use of systemic steroids
8. Treatment with any anti-diabetic medication other than insulin within 4 weeks of
transplant
9. Use of any investigational agent within 4 weeks of enrolment
10. Hypersensitivity to:
a) ibuprofen or to more than one non steroidal anti-inflammatory drug (NSAID).
b) medications belonging to the class of sulfonamides, such as sulfamethazine, sulfamethoxazole, sulfasalazine, nimesulide or celecoxib.
11. Pregnant or breast-feeding women; unwillingness to use effective contraceptive measures (females and males). (NB: pregnancy should be avoided in patients or partners during the first month after each treatment with the Investigational Product; no other specific warnings are described, considering even stricter general recommendations concerning pregnancy in transplanted patients, the treatment course of the Investigational Product, its PK profile, and the lack of significant adverse effects on mating performance and fertility in animal studies).
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E.5 End points |
E.5.1 | Primary end point(s) |
evaluate whether reparixin leads to improved transplant outcome as measured by glycaemic control following intra-hepatic infusion of pancreatic islets. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
14 or more consecutive days |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
evaluation of the mechanism of action |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
no experimental treatment |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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last visit of the last subject |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |