Clinical Trials Register

Summary
EudraCT Number:	2011-006201-10
Sponsor's Protocol Code Number:	REP0211
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-08-08
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2011-006201-10

A.3

Full title of the trial

A phase 3, multicenter, randomized, double-blind, parallel assignment study to assess the efficacy and safety of reparixin in pancreatic islet transplantation.

Studio di fase 3, multicentrico, randomizzato, doppio cieco, a gruppi paralleli per valutare l'efficacia e la tollerabilita' di reparixin nel trapianto di isole pancreatiche

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

reparixin in pancreatic islet transplantation

reparixin nel trapianto di isole pancreatiche

A.3.2

Name or abbreviated title of the trial where available

reparixin in pancreatic islet transplantation

reparixin nel trapianto di isole pancreatiche

A.4.1

Sponsor's protocol code number

REP0211

A.5.4

Other Identifiers

Name:

IND

Number:

67,023

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	DOMPE' s.p.a.
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Dompe' spa
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Dompe' spa
B.5.2	Functional name of contact point	Project Development Direction
B.5.3	Address:
B.5.3.1	Street Address	via San Martino
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20122
B.5.3.4	Country	Italy
B.5.4	Telephone number	0258383500
B.5.5	Fax number	0258383324
B.5.6	E-mail	info@dompe.it

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/11/912
D.3 Description of the IMP
D.3.1	Product name	reparixin
D.3.2	Product code	DF1681Y
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	reparixin
D.3.9.1	CAS number	266359-83-5
D.3.9.2	Current sponsor code	DF1681Y
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	33
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

pancreatic islet transplantation

trapianto di isole pancreatiche

E.1.1.1

Medical condition in easily understood language

pancreatic islet transplantation

trapianto di isole pancreatiche

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	14.1
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

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 assess whether reparixin leads to improved transplant outcome as measured by glycaemic control following intra-hepatic infusion of pancreatic islets in T1D patients. The safety of reparixin in the specific clinical setting will be also evaluated.

Obiettivo di questo studio clinico e' valutare se reparixin migliora l'esito clinico, misurato come controllo della glicemia, dopo infusione intra-epatica di isole pancreatiche in pazienti con diabete di tipo 1. Inoltre sara' valutata la tollerabilita' di reparixin nell'ambito clinico specifico.

E.2.2

Secondary objectives of the trial

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients aged 18-70 years given written informed consent who are eligible for a pancreatic islet transplantation program [clinical history of T1D with insulin-dependence for >=5 years, undetectable (<0.3 ng/mL) stimulated C-peptide levels] and planned to receive intrahepatic islet transplantation alone from a non-living donor with brain death.

Pazienti di eta' compresa tra 18 e 70 anni che abbiano dato il proprio consenso informato scritto e che sono eligibili ad un programma di trapianto di isole pancreatiche [anamnesi di diabete di tipo 1 con insulino dipendenza da >=5 anni, C-peptide stimolato non misurabile (<0.3ng/mL)] con previsione di trapianto intra-epatico di isole da donatore non vivente in stato di morte cerebrale.

E.4

Principal exclusion criteria

Recipients of any previous transplant (including previous islet transplantation), of islet from a non-heart beating donor will be excluded. Patients who have pre-transplant average daily insulin requirement >1 IU/kg/day, pre-transplant HbA1c >11%, inadequate renal reserve (calculated creatinine clearance < 60 mL/min according to the Cockcroft-Gault formula) or hepatic dysfunction (increased ALT/AST > 3 x upper limit of normal and increased total bilirubin > 3mg/dL) will be excluded as well. Also, patients will be excluded if they receive treatment for a medical condition requiring chronic use of systemic steroids or treatment with any anti-diabetic medication other than insulin within 4 weeks of transplant or any investigational agent within 12 weeks of enrolment. Patients with hypersensitivity to ibuprofen or to more than one non steroidal anti-inflammatory drug or to medications belonging to the class of sulfonamides (e.g. sulfamethazine, sulfamethoxazole, sulfasalazine, nimesulide or celecoxib) as well as pregnant or breast-feeding women or unwillingness to use effective contraceptive measures (females and males) will be excluded from study participation.

Saranno esclusi dallo studio i pazienti che hanno ricevuto un precedente trapianto (inclusi i riceventi di un precedente trapianto di isole pancreatiche) e i pazienti che riceveranno le isole da un donatore a cuore non-battente. Saranno inoltre esclusi i pazienti con un fabbisogno pre-trapianto di insulina > 1 IU/kg/giorno; una HbA1c > 11% pre-trapianto, una riserva renale inadeguata (clearance della creatinina <60 mL/min calcolata con la formula di Cockcroft-Gault) o con disfunzione epatica (ALT/AST superiori di tre volte il limite superiore di normalita' e bilirubina totale > 3 mg/dL). Inoltre, saranno esclusi i pazienti che hanno un trattamento per una patologia che richiede l'uso cronico di steroidi o il trattamento con farmaci antidiabetici oltre all'insulina nelle 4 settimane precedenti il trapianto o hanno ricevuto qualsiasi farmaco sperimentale nelle 12 settimane prima dell'arruolamento. Saranno altresi' esclusi i pazienti con ipersensibilita' all'ibuprofene o a piu' di un farmaco antiinfiammatorio non-steroideo o a farmaci della classe delle sulfonamidi (per esempio la sulfametazina, sulfametossazolo, nimesulide, celecoxib), le donne in stato di gravidanza o durante l'allattamento e donne e uomini che non desiderano utilizzare un metodo efficace di contraccezione.

E.5 End points

E.5.1

Primary end point(s)

assess whether reparixin leads to improved transplant outcome as measured by glycaemic control following intra-hepatic infusion of pancreatic islets

valutare se reparixin migliora l'esito clinico, misurato come controllo della glicemia, dopo infusione intra-epatica di isole pancreatiche

E.5.1.1

Timepoint(s) of evaluation of this end point

day 75 +/- 5 after the 1st islet infusion and day 365 +/- 14 after the last islet infusion

75 +/- 5 giorni dopo la 1° infusione e 365 +/- 14 giorni dopo l'ultima infusione

E.5.2

Secondary end point(s)

The proportion of insulin-independent patients; The proportion of patients who achieve and maintain an HbA1c <7.0% (or o reduction in HbA1c > 2%) AND are free of severe hypoglycaemic events; The proportion of patients receiving a 2nd islet infusion; Cumulative number of severe hypoglycaemic events; Change in average daily insulin requirements (absolute and % decrease from pre-transplant levels); HbA1c % (absolute and % decrease from pre-transplant levels); Basal (fasting) and 0 to 120 min time course of glucose, C-peptide and insulin derived from the MMTT; beta-cell function as assessed by beta-score and Transplant Estimated Function (TEF)

Proporzione di pazienti con insulino-indipendenza; Proporzione di pazienti che raggiungono e mantengono livelli di emoglobina glicata (HbA1c) <7.0% (o una riduzione della HbA1c > 2%) E non hanno episodi di ipoglicemia severa; Proporzione di pazienti che ricevono una 2° infusione di isole pancreatiche; Numero cumulativo di episodi di ipoglicemia severa; Variazione del fabbisogno medio giornaliero di insulina (valori assoluti e percentuale di riduzione rispetto ai valori pre-trapianto); Livelli di HbA1c (valori assoluti e percentuale di riduzione rispetto ai valori pre-trapianto); Livelli di glucosio, C-peptide e insulina al basale (a digiuno) e curva tempo-risposta da 0 a 120 minuti derivata dal Mixed Meal Tolerance Test; Funzione delle beta-cellule misurata attraverso il beta-score e il Transplant Estimated Function

E.5.2.1

Timepoint(s) of evaluation of this end point

day 75+/-5 after the 1st and 2nd islet infusion and day 365+/-14 after last islet infusion; day 365+/-14 after last islet infusion; day 365+/-14 after the 1st islet infusion; day 365+/-14 after last islet infusion; day 75+/-5 after the 1st and 2nd islet infusion and day 365+/-14 after last islet infusion; day 75+/-5 after the 1st and 2nd islet infusion and day 365+/-14 after last islet infusion; day 75+/-5 after the 1st and 2nd islet infusion and day 365+/-14 after last islet infusion

75+/-5 giorni dopo la 1° e 2° infusione e 365+/-14 giorni dopo l'ultima infusione; 365+/-14 giorni dopo l'ultima infusione; 365+/-14 giorni dopo la 1° infusione; 365+/-14 giorni dopo l'ultima infusione; 75+/-5 giorni dopo la 1° e 2° infusione e 365+/-14 giorni dopo l'ultima infusione; 75+/-5 giorni dopo la 1° e 2° infusione e 365+/-14 giorni dopo l'ultima infusione; 75+/-5 giorni dopo la 1° e 2° infusione e 365+/-14 giorni dopo l'ultima infusione

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

evaluation of mechanism of action

valutazione del meccanismo d'azione

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

United States

E.8.7

Trial has a data monitoring committee

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

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2012-07-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-05-10

P. End of Trial
P.	End of Trial Status	Completed

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