Clinical Trials Register

Summary
EudraCT Number:	2010-019630-28
Sponsor's Protocol Code Number:	C10-001
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2012-03-08
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

2010-019630-28

A.3

Full title of the trial

A Randomized, Open-Label, Multicenter Trial to Determine Safety and Efficacy of Eculizumab in the Prevention of Antibody Mediated Rejection (AMR) in Living Donor Kidney Transplant Recipients Requiring Desensitization Therapy.

Studio randomizzato, in aperto, multicentrico volto a stabilire la sicurezza e l'efficacia di eculizumab nella prevenzione del rigetto mediato da anticorpi (AMR, Antibody Mediated Rejection) in beneficiari di trapianto renale da donatori viventi, necessitanti di terapia di desensibilizzazione.

A.3.1

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

Open Label controlled trial of eculizumab in the prevention of AMR in living donor kidney transplant recipients requiring desensitization.

Studio in aperto controllato su eculizumab per la prevenzione di AMR in beneficiari di trapianto di rene da donatore vivente che necessitano di desensibilizzazione.

A.4.1

Sponsor's protocol code number

C10-001

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	ALEXION PHARMACEUTICALS
B.1.3.4	Country	United States
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	ALEXION PHARMACEUTICALS INC
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	ALEXION EUROPE SAS
B.5.2	Functional name of contact point	EUROPEAN CLINICAL TRIAL INFORMATION
B.5.3	Address:
B.5.3.1	Street Address	25 BOULEVARD DE L'AMIRAL BRUIX
B.5.3.2	Town/ city	PARIGI
B.5.3.3	Post code	75016
B.5.3.4	Country	France
B.5.4	Telephone number	+33 1 5364 3941
B.5.5	Fax number	+33 1 5364 3820
B.5.6	E-mail	clinicaltrials.eu@alxn.com

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	Yes
D.2.1.1.1	Trade name	SOLIRIS*EV 1FL 300MG 30ML
D.2.1.1.2	Name of the Marketing Authorisation holder	ALEXION PHARMA ITALY
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
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	ECULIZUMAB
D.3.9.1	CAS number	219685-50-4
D.3.9.2	Current sponsor code	h5g1.1-mAb
D.3.9.3	Other descriptive name	Anti-C5 anitbody
D.3.9.4	EV Substance Code	SUB25187
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	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
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	Yes
D.3.11.13.1	Other medicinal product type	anticorpo monoclonale

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Antibody mediated rejection after kidney transplant

Reazione di rigetto a seguito di trapianto renale anticorpo mediata

E.1.1.1

Medical condition in easily understood language

Kidney transplant rejection

Rigetto di trapianto renale

E.1.1.2

Therapeutic area

Body processes [G] - Immune system processes [G12]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	SOC
E.1.2	Classification code	10021428
E.1.2	Term	Immune system disorders
E.1.2	System Organ Class	10021428 - Immune system disorders

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

To evaluate the safety and efficacy of eculizumab to prevent AMR in sensitized recipients of living donor kidney transplants requiring desensitization therapy.

Valutare la sicurezza e l’efficacia di eculizumab per la prevenzione dell’AMR in beneficiari sensibilizzati di trapianti renali da donatori viventi che richiedano terapia di desensibilizzazione

E.2.2

Secondary objectives of the trial

Safety and efficacy

Sicurezza ed efficacia

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female patients ≥18 years old 2. Patients with Stage IV or Stage V chronic kidney disease who will receive a kidney transplant from a living donor to whom they are sensitized and require desensitization prior to transplantation 3. History of prior exposure to HLA: a. Prior solid organ or tissue allograft b. Pregnancy c. Blood transfusion d. Prior exposure to specific donor’s HLA 4. The presence of DSA by the SAB assay (Luminex LabScreen assay), as described by the manufacturer’s package insert 5. Positive CDC cross match (current or historic) and BFXM and TFXM < 450mcs OR have a negative CDC cross match AND a BFXM or TFXM > 300 and < 450mcs. No patient may have a BFXM or TFXM > 450mcs. 6. Able to understand the informed consent form and willing to comply with study procedures 7. Female patients of child-bearing potential must have a negative pregnancy test (serum beta-hCG) and must be practicing an effective, reliable and medically approved contraceptive regimen while on eculizumab treatment and for up to 5 months following discontinuation of treatment.

1. Pazienti maschili o femminili di età ≥18 anni 2. Pazienti affetti da insufficienza renale cronica di stadio IV o V che saranno sottoposti a un trapianto renale da un donatore vivente al quale siano sensibilizzati e che richiedano terapia di desensibilizzazione prima del trapianto. 3. Storia di precedente esposizione agli HLA: a. Pregresso allotrapianto di organo solido o tessuto b. Gravidanza c. Trasfusione di sangue d. Pregressa esposizione agli HLA donatore-specifici 4. Presenza di DSA rilevati mediante SAB assay (Luminex LabScreen assay), come descritto nel foglio illustrativo del produttore 5. Positività al crossmatch per CDC (attuale o storico) e BFXM e TFXM < 450mcs OPPURE negatività al crossmatch per CDC E con BFXM o TFXM > 300 e < 450mcs. Il BFXM o TFXM non può risultare > 450mcs. 6. Paziente in grado di comprendere il modulo di consenso informato e disposto a seguire le procedure dello studio 7. Le pazienti di sesso femminile potenzialmente fertili devono risultare negative al test di gravidanza (beta hCG nel siero) e adottare un metodo contraccettivo efficace, affidabile e clinicamente approvato durante il trattamento con eculizumab e fino a 5 mesi dopo l’interruzione del trattamento.

E.4

Principal exclusion criteria

1. Has received treatment with eculizumab at any time prior to enrolling in this study 2. ABO incompatible with living donor 3. History of severe cardiac disease (e.g., New York Heart Association [NYHA] Functional Class III or IV, myocardial infarction ≤ 6 months of randomization, ventricular tachyarrhythmias requiring ongoing treatment, unstable angina or other significant cardiovascular diseases) 4. Prior splenectomy 5. Has a known bleeding disorder 6. Has any active bacterial or other infection which is clinically significant in the opinion of the Investigator and is a contraindication to transplantation 7. Has participated in any other investigational drug study or was exposed to an investigational drug or device within 30 days of screening 8. Has received rituximab (Rituxan) ≤ 3 months prior to screening 9. Has received bortezomib (Velcade) ≤ 3 months prior to screening 10. Has received alemtuzumab (Campath) ≤ 6 months prior to screening 11. Hypersensitivity to eculizumab, to murine proteins or to one of the excipients 12. History of illicit drug use or alcohol abuse within the previous year 13. Unresolved meningococcal disease 14. Current cancer or a history of cancer within the 5 years prior to screening with the exception of patients who have successfully treated nonmetastatic basal or squamous cell carcinoma of the skin; carcinoma in situ of the cervix; or breast carcinoma in situ 15. Any medical condition that, in the opinion of the Investigator, might interfere with the patient’s participation in the study, poses an added risk for the patient, or confounds the assessment of the patient 16. Active infection with Hepatitis B (HBV), Hepatitis C (HCV) or human immunodeficiency virus (HIV)

1. Assunzione di eculizumab prima dell’arruolamento nel presente studio 2. ABO incompatibilità con il donatore vivente 3. Storia di grave disturbo cardiaco (p.e. infarto miocardico di classe funzionale III o IV della New York Heart Association [NYHA] a distanza di ≤ 6 mesi dalla randomizzazione, tachiaritmie ventricolari necessitanti di trattamento permanente, angina instabile o altri disturbi cardiovascolari significativi) 4. Pregressa splenectomia 5. Pregresso disturbo emorragico 6. Infezione batterica attiva o di altra natura che sia clinicamente significativa a giudizio dello Sperimentatore e che rappresenti una controindicazione al trapianto 7. Partecipazione ad altri studi aventi ad oggetto il farmaco sperimentale o esposizione a un farmaco o a un dispositivo sperimentale nei 30 giorni precedenti allo screening 8. Assunzione di rituximab (Rituxan) ≤ 3 mesi prima dello screening 9. Assunzione di bortezomib (Velcade) ≤ 3 mesi prima dello screening 10. Assunzione di alemtuzumab (Campath) ≤ 6 mesi prima dello screening 11. Ipersensibilità a eculizumab, alle proteine del topo (murine) o a uno degli eccipienti 12. Storia di uso di farmaci illeciti o abuso di alcol nell’anno precedente 13. Malattia meningococcica irrisolta 14. Attuale cancro o storia di cancro nei 5 anni precedenti lo screening a eccezione dei pazienti che siano stati trattati con successo per carcinoma della pelle non metastatico al basale o a cellule squamose; carcinoma in situ della cervice o del seno 15. Qualsivoglia patologia che, a giudizio dello Sperimentatore, potrebbe interferire con la partecipazione allo studio del paziente, porre un ulteriore rischio per il paziente o confondere la valutazione del paziente medesimo 16. Infezione attiva con epatite B (HBV), epatite C (HCV) o virus dell’immunodeficienza umana (HIV)

E.5 End points

E.5.1

Primary end point(s)

To evaluate the safety and efficacy of eculizumab to prevent AMR in sensitized recipients of living donor kidney transplants requiring desensitization therapy

Valutare la sicurezza e l’efficacia di eculizumab per la prevenzione dell’AMR in beneficiari sensibilizzati di trapianti renali da donatori viventi che richiedano terapia di desensibilizzazione.

E.5.1.1

Timepoint(s) of evaluation of this end point

9 weeks

9 settimane

E.5.2

Secondary end point(s)

Cumulative incidence of AMR that occur between week 9and month 12

Incidenza totale di AMR che intervengono tra 9 settimana e 12 mesi dopo il trapianto

E.5.2.1

Timepoint(s) of evaluation of this end point

1 year

1 anno

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

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

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Cura Standard

English SOC

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

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

Canada

United States

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

LPLV

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)

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)

Not different from the expected normal treatment ot that condition

I soggetti verranno trattati con i trattamenti standard applicati rispetto alle loro condizioni

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

2012-02-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-09-28

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2015-11-13

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