Clinical Trials Register

Summary
EudraCT Number:	2007-002092-14
Sponsor's Protocol Code Number:	A0485-CL-E201
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:	2007-11-13
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2007-002092-14

A.3

Full title of the trial

Efficacy and safety of Alefacept in combination with Tacrolimus, Mycophenolate Mofetil and Steroids in de-novo kidney transplantation - a multicenter, randomized, double-blind, placebo controlled, parallel group study

A.3.2

Name or abbreviated title of the trial where available

Proof of Concept with Alefacept in Kidney Transplantation

Proof of Concept with Alefacept in Kidney Transpla

A.4.1

Sponsor's protocol code number

A0485-CL-E201

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	Astellas Pharma Europe B.V.
B.1.3.4	Country	Netherlands
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	alefacept
D.3.2	Product code	A0485
D.3.4	Pharmaceutical form	Powder for solution for injection
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	alefacept
D.3.9.1	CAS number	222535-22-0
D.3.9.2	Current sponsor code	A0485
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.3	Concentration number	15
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)	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	Yes
D.3.11.13.1	Other medicinal product type	Non Applicabile
D.IMP: 2
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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	alefacept
D.3.2	Product code	A0485
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	alefacept
D.3.9.1	CAS number	222535-22-0
D.3.9.2	Current sponsor code	A0485
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.3	Concentration number	15
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)	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	Yes
D.3.11.13.1	Other medicinal product type	Non Applicabile

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	Powder for solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Powder for solution for injection
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

kidney transplantation

trapianto renale

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

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	10038533
E.1.2	Term	Renal transplant
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this study is to evaluate the efficacy and safety of alefacept in a kidney transplant population. Data suggests that 12 weeks of treatment with alefacept in combination with tacrolimus, mycophenolate mofetil (MMF) and steroids may be more effective than and as safe as a combination therapy of tacrolimus with MMF and steroids. Effectiveness will be measured as the occurrence of and time to biopsy proven acute rejection at six months assessed locally.

L'obiettivo primario di questo studio e' valutare l'efficacia e la sicurezza di alefacept in una popolazione trapiantata di rene. I dati in nostro possesso suggeriscono che 12 settimane di trattamento con alefacept in combinazione con tacrolimus, micofenolato mofetile (MMF) e steroidi possono essere piu' efficaci e ugualmente sicure della combinazione di tacrolimus con MMF e steroidi. L'attivita' sara' misurata nel verificarsi degli episodi di rigetto acuto, confermati istologicamente, e nel loro tempo di insorgenza durante i primi sei mesi dal trapianto, valutati localmente.

E.2.2

Secondary objectives of the trial

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

PHARMACOKINETIC/PHARMACODYNAMIC:
Vers:
Date:
Title:
Objectives:

FARMACOCINETICA/FARMACODINAMICA:
Vers:
Data:
Titolo:
Obiettivi:

E.3

Principal inclusion criteria

Subject is eligible for the study if all of the following apply: 1. Subject with end stage kidney disease who is a suitable candidate for primary kidney transplantation or re-transplantation. 2. Male or female subject at least 18 years of age and younger than 65 years. 3. Subject receiving a kidney transplant from a non-human leukocyte antigen (non-HLA) identical living donor or an HLA identical/non-HLA identical deceased donor between 5 and 59 years of age with compatible AB0 blood type. 4. Female subjects of childbearing potential must have a negative serum pregnancy test at enrollment and must agree to maintain effective birth control during the study. Effective birth control is defined as surgically sterilized, hormonal contraception or total abstinence at the discretion of the investigator in cases where age, career, lifestyle or sexual orientation ensures compliance of the subject. 5. Subject has been fully informed and has given written informed consent. Subject unable to write and/or read but who fully understands the oral information given by the investigator (or nominated representative) has given oral informed consent witnessed in writing by an independent person.

I soggetti sono eligibili in questo studio se soddisfano tutti i seguenti criteri: 1. Soggetti con malattia renale in fase terminale candidati a trapianto renale primario o re-trapianto. 2. Soggetti di sesso maschile o femminile di eta' compresa tra 18 anni e 65 anni. 3. Soggetti che ricevono un trapianto di rene da donatore vivente non-HLA identico oppure da donatore cadavere HLA identico/non-HLA identico tra 5 e 59 anni di eta' e di gruppo sanguigno AB0 compatibile. 4. Soggetti di sesso femminile in eta' fertile con test sierologico di gravidanza negativo al momento dell'arruolamento e d'accordo a mantenere un efficace controllo delle nascite durante lo studio. Per efficace controllo delle nascite si intende sterilizzazione chirurgica, contraccezione ormonale o totale astinenza; si lascia alla discrezione dello sperimentatore la scelta del metodo che, relativamente all'eta', carriera, stile di vita e abitudini sessuali del soggetto assicuri la compliance del soggetto stesso. 5. Soggetti che siano stati dettagliatamente informati e abbiano dato il loro consenso informato scritto. Soggetti incapaci di scrivere e/o leggere, in grado pero' di comprendere appieno le informazioni verbali date loro dallo sperimentatore (o rappresentante delegato), che abbiano dato il loro consenso informato verbale testimoniato per iscritto da una persona indipendente.

E.4

Principal exclusion criteria

Subject will be excluded from participation if any of the following apply: 1. Subject has a PRA grade > 20% in the previous 6 months and/or had had a previous graft survival shorter than 1 year due to immunological reasons. 2. Subject has received a kidney transplant from a non-heart beating donor. 3. Subject has received a kidney from a 50 - 59 year old donor with two of the following three factors: history of hypertension, cerebrovascular accident as cause of death, final pre-procurement serum creatinine >1.5 mg/dL (United Network for Organ Sharing UNOS expanded criteria donor). 4. Subject has previously received or is receiving an organ transplant other than kidney. 5. Cold ischemia time of the donor kidney is ≥ 30 hours. 6. Subject is pregnant or breastfeeding. 7. Subject has significant liver disease, defined as having continuously elevated AST and/or ALT levels greater than 2 times the upper value of the normal range. 8. Subject has known hypersensitivity to alefacept, tacrolimus, macrolide antibiotic, mycophenolate mofetil, corticosteroids or any of the product excipients. 9. Subject has received intravenous immunoglobulin (IVIG) therapy in the three months prior to first dose of study drug. 10. Subject requires initial sequential or parallel therapy with immunosuppressive antibody preparation. 11. Subject requires ongoing dosing with a systemic immunosuppressive drug at study entry for any reason other than kidney transplantation. 12. Subject or donor is known to be HIV positive. 13. Subject with malignancy or history of malignancy in the past five years, except non-metastatic basal or squamous cell carcinoma of the skin that has been treated successfully. 14. Subject has significant, uncontrolled concomitant infections or any other unstable medical condition that could interfere with the study objectives. 15. Subject is participating or has participated in another clinical trial and/or is taking or has been taking an investigational drug in the past 28 days. 16. Subject is unlikely to comply with the visit schedule in the protocol. 17. Subject has any form of substance abuse, psychiatric disorder or condition that, in the opinion of the investigator may invalidate communication with the investigator.

I soggetti saranno esclusi dalla partecipazione se si verifica uno dei seguenti criteri: 1. Soggetti con PRA > 20% nei precedenti 6 mesi e/o il cui organo precedentemente trapiantato sia sopravvissuto meno di 1 anno a causa di motivi immunologici. 2. Soggetti che abbiano ricevuto un trapianto di rene da un donatore a cuore non battente. 3. Soggetti che abbiano ricevuto un rene da un donatore di eta' compresa tra 50 e 59 anni che presenti due dei seguenti tre fattori: storia di ipertensione, incidente cerebrovascolare come causa di morte, creatinina sierica al prelievo dell'organo >1.5 mg/dL (United Network for Organ Sharing UNOS criteri di donazione estesi). 4. Soggetto che abbia precedentemente ricevuto o stia ricevendo un trapianto d'organo diverso dal rene. 5. Tempo di ischemia fredda del rene donato ≥ 30 hours. 6. Soggetto in gravidanza o allattamento. 7. Soggetto con malattia epatica rilevante, definita come livelli di AST e/o ALT costantemente superiori a 2 volte il limite superiore dell'intervallo di normalita'. 8. Soggetti con ipersensibilita' nota ad alefacept, tacrolimus, antibiotici macrolidi, micofenolato mofetile, corticosteroidi o ciascun loro eccipiente. 9. Soggetti che abbiano ricevuto immunoglobuline endovena (e.v. IG) nei tre mesi precedenti alla prima dose di farmaco sperimentale. 10. Soggetti che necessitino di terapia sequenziale o in parallelo con anticorpi ad azione immunosoppressiva. 11. Soggetti che stiano ricevendo terapia con un farmaco immunosppressivo sistemico al momento dell'arruolamento per ciascun motivo diverso dal trapianto di rene. 12. Soggetto o donatore noti per essere HIV positive. 13. Soggetto con neoplasia o storia di neoplasia negli ultimi cinque anni, ad eccezione del carcinoma basale non-metastatico o a cellule squamose della pelle trattato con successo. 14. Soggetto con infezioni concomitanti significative e incontrollate o qualsiasi altra condizione medica instabile che possa interferire con gli obiettivi dello studio. 15. Soggetto che stia partecipando o abbia partecipato ad uno studio clinico e/o stia assumendo o abbia assunto un farmaco sperimentale negli ultimi 28 giorni. 16. Soggetto la cui collaborazione al protocollo e attinenza allo schema delle visite sia improbabile. 17. Soggetto con qualsiasi forma di tossicodipendenza, disturbi psichiatrici o condizioni che, a giudizio dello sperimentatore, possano invalidare la comunicazione con lo sperimentatore stesso.

E.5 End points

E.5.1

Primary end point(s)

• Incidence (Kaplan-Meier estimate) of biopsy-confirmed acute rejection (Banff Grade ≥ 1) as assessed by local reading at month 6 (cumulative event rate)

• Incidenza (stima Kaplan-Meier) del rigetto acuto confermato da biopsia (Banff Grade ≥ 1) valutato localmente al Mese 6 (percentuale cumulativa dell'evento)

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

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

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

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.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Information not present in EudraCT

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

ultima visita dell'ultimo soggetto

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.1.3

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

200

F.4.2.2

In the whole clinical trial

200

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

2007-11-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2007-10-25

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2009-05-30

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials