Clinical Trials Register

Summary
EudraCT Number:	2011-004223-12
Sponsor's Protocol Code Number:	CT-1KIDN-01
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2012-07-26
Trial 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

Spain - AEMPS

A.2

EudraCT number

2011-004223-12

A.3

Full title of the trial

A pilot, randomised, double blind, placebo-controlled, parallel groups, clinical trial to investigate the efficacy and safety of Cardiotrophin-1 (CT-1) in kidney transplantation.

Ensayo clínico, piloto, aleatorizado, doble ciego, controlado con placebo, de grupos paralelos, para investigar la eficacia y seguridad de cardiotrofina-1 (CT-1) en el transplante renal.

A.3.1

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

A pilot clinical study in kidney transplant to assess the efficacy and safety of cardiotrophin-1.

Ensayo clínico piloto en transplante de riñón para evaluar la eficacia y seguridad de cardiotrofina-1.

A.4.1

Sponsor's protocol code number

CT-1KIDN-01

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	Digna Biotech S.L.
B.1.3.4	Country	Spain
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	Digna Biotech S.L.
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Digna Biotech S.L.
B.5.2	Functional name of contact point	Trial Manager
B.5.3	Address:
B.5.3.1	Street Address	C/ Boix y Morer 6-8º
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28003
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34911852510NA
B.5.5	Fax number	+34911852519NA
B.5.6	E-mail	jcamara@dignabiotech.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	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/3/06/396
D.3 Description of the IMP
D.3.1	Product name	Cardiotrophin-1
D.3.2	Product code	CT-1
D.3.4	Pharmaceutical form	Solution for perfusion of organs
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Other use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Cardiotrophin
D.3.9.1	CAS number	NA
D.3.9.2	Current sponsor code	CT-1
D.3.9.3	Other descriptive name	NA
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	0.5
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	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	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 perfusion of organs
D.8.4	Route of administration of the placebo	Other use (Noncurrent)

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Kidney transplantation.

Trasplante renal.

E.1.1.1

Medical condition in easily understood language

Kidney transplant.

Trasplante de riñón.

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10023438
E.1.2	Term	Kidney 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

To assess the effect of CT-1 on kidney function after transplant through the incidence of functional Delayed Graft Function (fDGF).

Valorar el efecto de CT-1 sobre la función renal después del trasplante mediante la incidencia de la función retrasada del injerto funcional (Funtional Delayed Graft function, fDGF).

E.2.2

Secondary objectives of the trial

?To assess the effect of CT-1 on kidney function after
transplant through:
-The DGF rate, defined as the need of dialysis during
the first week after transplantation.
-The glomerular filtration rate post-transplant.
-Serum creatinine levels post-transplant.
?The incidence and severity of acute rejection within 30 days post-transplant.
?To assess kidney damage by measuring the levels of serum and urine biomarkers.
?To assess the economic impact of CT-1 on kidney transplant. through the days of hospitalization after transplant.
?To assess the safety of CT-1 in kidney transplant.

?Evaluar el efecto de CT-1 sobre la función renal
después del trasplante, mediante:
-Tasa de DGF, definida como la necesidad de diálisis durante la primera semana después del trasplante.
-Tasa de filtración glomerular post-trasplante.
-Niveles de creatinina sérica post-trasplante.
?Incidencia y severidad del rechazo agudo en los 30 días post-trasplante.
?Evaluar el daño renal mediante los niveles de biomarcadores séricos y urinarios.
?Evaluar el impacto económico de CT-1 en el trasplante renal mediante los días de hospitalización después del trasplante.
?Valorar la seguridad de CT-1 en el trasplante renal.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

A donor will be suitable only if all of the following criteria apply:
1.Heart-beating donors (male or female);
2.Donor aged ? 60 or donor aged 50-59 years and fulfilling 2 of the following 3 criteria:
a.Serum creatinine more than 1.5 mg/dl.
b.Death due to cerebrovascular accident.
c.History of high blood pressure.

A patient (Kidney recipient) will be eligible only if all of the following criteria apply:
1.Males or females aged 18 to 70 years without restricted legal competence and being able to comply with the study requirements.
2.Females of Childbearing Potential must have a negative urine pregnancy test at Screening/Treatment visit and must be willing to use one medically approved form of birth control while on study and for at least 28 days after taking kidney transplant.
3.Subject capable of giving written informed consent.

Un donante solo será adecuado si cumple los siguientes criterios:
1.Donantes con corazón latiendo (hombre o mujer);
2.Edad del donante ? 60 años o donante de 50 a 59 años de edad que cumpla 2 de los 3 criterios siguientes:
a.Creatinina sérica superior a 1,5 mg/dl.
b.Muerte secundaria a accidente cerebrovascular.
c.Antecedentes de hipertensión arterial.

Un paciente (receptor del riñón) será elegible si cumple los siguientes criterios:
1.Hombres o mujeres de 18 a 70 años sin restricciones legales de competencia y con capacidad para cumplir con los procedimientos del estudio.
2. Las mujeres potencialmente fértiles deben presentar una prueba de embarazo en orina negativa y deben estar dispuestas a utilizar un método anticonceptivo médicamente aprobado, durante el estudio y hasta un mínimo de 28 días después del trasplante.
3.Sujeto capaz de dar el consentimiento informado.

E.4

Principal exclusion criteria

A donor will not be suitable if any of the following criteria apply:
1.Infection by HIV, HBV and/or HCV viruses.
2.Non-heart beating donors.
3.Kidney from a living donor.
4.Cold ischemic time >24 hours.
5.Incompatible AB0 type with recipient.
6.Positive crossmatch with recipient.
7.Kidney maintained by pulsatile machine perfusion.

A patient (recipient) will not be eligible if any of the following criteria apply:
1.Previous or current myelodysplastic or proliferative disorders.
2.History of cancer within the last 5 years with the exception of adequately treated basal cell or squamous cell carcinoma in situ.
3.Administration of any investigational drug in the period 0 to 90 days before entry to the study.
4.Pregnant or breastfeeding women.
5.Patient is scheduled to undergo multiorgan transplantation.
6.Chronic or ongoing active infectious disease requiring systemic treatment.
7.Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months from screening, congestive heart failure of worse than grade II New York criteria.
8.Significant concurrent, uncontrolled medical condition including, but not limited to, hepatic, cerebrovascular, haematological, gastrointestinal, endocrine, pulmonary, neurological, psychiatric disease, or evidence of demyelinating disease or concurrent sepsis or active bacterial infection.
9.Any other condition which in the principal investigator?s opinion would make patient unsuitable for study participation.

Un donante no será adecuado si cumple alguno de los siguientes criterios:
1.Infección por VHB, VHC y/o VIH.
2.Donantes en asistolia.
3.Riñón de donante vivo.
4.Tiempo de isquemia fría >24 horas.
5.Grupo sanguíneo AB0 incompatible.
6.Prueba cruzada donante-receptor positiva.
7.Riñón mantenido mediante perfusión pulsátil.

Un paciente (receptor) no será elegible si cumple alguno de los siguientes criterios:
1.Trastorno mielodisplásico o proliferativo actual o previo.
2.Neoplasia maligna, actual o en los 5 años anteriores a la inclusión, con la excepción de carcinoma in situ de células escamosas o basocelular adecuadamente tratado.
3. Sujetos que hayan recibido tratamiento un tratamiento experimental en los 90 días anteriores a su inclusión en el estudio.
4.Mujeres embarazadas o en período de lactancia.
5. Está previsto que va a recibir un trasplante multiorgánico.
6.Infección activa o crónica, que requiere tratamiento sistémico.
7.Cardiopatía clínicamente importante, como angina inestable, infarto de miocardio agudo en un plazo de 6 meses antes de la selección, insuficiencia cardiaca congestiva de grado superior al grado II de los criterios New York.
8.Proceso médico no controlado concomitante de importancia, como, entre otras, enfermedades renales, hepáticas, hematológicas, gastrointestinales, endocrinas, pulmonares, neurológicas, cerebrales o psiquiátricas, o signos de enfermedad desmielinizante.
9.Cualquier otra condición que, en opinión del investigador principal, haga que el paciente no sea adecuado para participar en el estudio.

E.5 End points

E.5.1

Primary end point(s)

Incidence of Delayed Graft Function (DGF) measured as a failure of the serum creatinine to decrease by at least 10% daily on 3 consecutive days during the first week after transplant, irrespective of dialysis requirements, but discounting creatinine decrements because of dialysis itself.

Incidencia de DGF medida como un medida como el fallo para disminuir, al menos un 10% al día en 3 días consecutivos, los niveles de creatinina sérica durante la primera semana posterior al trasplante renal, independientemente de los requerimientos de diálisis, pero descontando las reducciones de creatinina debidas a la diálisis.

E.5.1.1

Timepoint(s) of evaluation of this end point

1 week after kidney transplant.

1 semana posterior al transplante renal.

E.5.2

Secondary end point(s)

?DGF rate defined as the need of dialysis during the first week after transplantation.
?Estimated glomerular filtration rate (eGFR*) at post-transplant at days 1, 3, 5, 7, 14 and 30 post-trasplant.
*Calculated according to ?Modification of diet in renal disease equation for glomerular filtration rate (MDRD)?
?Number of dialysis sessions through Day 7, 14, and 30.
?Mean serum creatinine at Days 1, 3, 5, 7, 14, and 30.
?Incidence and severity of biopsy-proven acute rejection within 30 days.
?At days 1, 3, 5, 7 and 14; there will be determined the levels of serum neutrophil gelatinase-associated lipocalin (S-NGAL) and urine markers such as total protein, albumin, cystatin C, beta-2 microglobulin, kidney injury molecule (KIM-1), clusterin (CLU), trefoil factor 3 (TTF 3), NGAL (U-NGAL), Ganglioside M2 activator protein (GM2AP), regenerating islet-derived protein III beta (Reg IIIb) and gelsolin. Additional serum and urine markers could be determined according to the AKI state of the art.
?Days of hospitalization.
?The investigator will assess the safety based on AEs and the laboratory evaluation across the study.

?Tasa de DGF, definida como la necesidad de diálisis durante la primera semana después del trasplante.
?Tasa de filtración glomerular estimada (TFGe*) los días 1, 3, 5, 7, 14 y 30 post-trasplante.
*Calculada mediante la "ecuación de modificación de la dieta en la enfermedad renal para la TFG"
?Número de sesiones de diálisis los días 7, 14 y 30.
?Creatinina sérica media los días 1, 3, 5, 7, 14, y 30.
?Incidencia y severidad del rechazo agudo demostrado mediante biopsia durante los 30 días post-trasplante.
?Los días 1, 3, 5, 7 y 14 post-trasplante se determinarán los niveles de lipocalina asociada a la gelatinasa de los neutrófilos en suero (S-NGAL) y marcadores urinarios como proteínas totales, albúmina, cistatina C, beta-2 microglobulina, molécula 1 de daño renal (KIM-1), clusterina (CLU), factor 3 trilobular (TTF 3), NGAL en orina (U-NGAL), proteína activadora del gangliósido M2 (GM2AP), proteína regeneradora III beta derivada de islotes (Reg IIIb) y gelsolina. Marcadores séricos y urinarios adicionales podrían ser analizados según el estado del conocimiento del daño renal agudo.
?Días de hospitalización.
?La seguridad se valorará mediante los acontecimientos adversos y los parámetros de laboratorio durante el estudio.

E.5.2.1

Timepoint(s) of evaluation of this end point

30 days post-trasplant

30 días post-transplante

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

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

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

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

Last Patient Last Visit

Última Visita Último Paciente

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.1.1.1

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.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)

Expected normal treatment.

Tratamiento habitual según práctica clínica.

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

2012-08-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-07-26

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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