Clinical Trials Register

Summary
EudraCT Number:	2010-019243-19
Sponsor's Protocol Code Number:	004-09
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:	2014-06-02
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

2010-019243-19

A.3

Full title of the trial

Pilot Study of BB3 to Improve Renal Function in Patients with Signs and Symptoms of Significant Renal Injury after Kidney Transplantation from Donors after Cardiac Death

Estudio Piloto con BB3 para Mejorar la Función Renal en Pacientes con Signos y Síntomas de Lesión Renal Significativa después del Trasplante de Riñón por parte de Donantes tras Muerte Cardíaca

A.3.1

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

Exploratory Study of BB3 to Improve Renal Function in Patients with Signs and Symptoms of Significant Renal Injury after Kidney Transplantation from Donors after Cardiac Death

Estudio exploratorio con BB3 para Mejorar la Función Renal en Pacientes con Signos y Síntomas de Lesión Renal Significativa después del Trasplante de Riñón por parte de Donantes tras Muerte Cardíaca

A.3.2

Name or abbreviated title of the trial where available

BB3 in kidney transplantation Version 8.0

BB3 en trasplante de riñón

A.4.1

Sponsor's protocol code number

004-09

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01561599

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	Angion Biomedica Corp.
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	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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	Pharmalys Ltd
B.5.2	Functional name of contact point	Marieme Ba
B.5.3	Address:
B.5.3.1	Street Address	2 Oaks Court, Warwick Road
B.5.3.2	Town/ city	Borehamwood
B.5.3.3	Post code	WD6 1GS
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	02080909621
B.5.5	Fax number	02080909629
B.5.6	E-mail	marieme.ba@pharmalys.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	10-3075
D.3 Description of the IMP
D.3.1	Product name	BB3
D.3.2	Product code	BB3
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 drip use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BB3
D.3.9.1	CAS number	1070881-42-3
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
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 drip use (Noncurrent)

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients suffering from end-stage renal disease, receiving a donor kidney from donors after cardiac death

Pacientes con enfermedad renal terminal, recibiendo un riñón de donante tras muerte cardiaca.

E.1.1.1

Medical condition in easily understood language

Patients suffering from end-stage renal disease, receiving a donor kidney from donors after cardiac death

Pacientes con enfermedad renal terminal, recibiendo un riñón de donante tras muerte cardiaca.

E.1.1.2

Therapeutic area

Not possible to specify

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	LLT
E.1.2	Classification code	10014647
E.1.2	Term	End stage renal failure
E.1.2	System Organ Class	100000004857

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 primary objective of this study is to evaluate the safety and efficacy of BB3 compared to placebo in improving renal function in the immediate post-transplant period in patients who have received DCD (Donor after Cardiac Death) kidney transplantation.

El objetivo principal de este estudio es evaluar la seguridad y la eficacia de BB3 en comparación con placebo en la mejora de la función renal en el período inmediatamente posterior al trasplante en pacientes que han recibido un trasplante de riñón después de muerte cardiaca (DMC).

E.2.2

Secondary objectives of the trial

None

Ninguno

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

To take advantage of the availability of non-paired kidneys, a sub-study of non-paired kidneys will be performed for 10 patients.

Para aprovechar las ventajas de la disponibilidad de riñones no parejos, se realizará un sub-estudio delos riñones no emparejados en 10 pacientes.

E.3

Principal inclusion criteria

1. Subjects must sign the informed consent document prior to performance of any study related procedure including the Screening procedure.
2. Males and females ? 18 years of age.
3. Had renal transplantation due to end stage disease requiring chronic dialysis.
4. Study drug can be administered within 6 to 36 hours after transplantation.
5. Received kidney from donor after cardiac death.
6. DCD kidney fulfills the clinical site's criteria for transplantation.
7. Creatinine clearance from the transplanted kidney over a 2-hour collection period is <10 mL/min., OR no urine output or < 50 cc/H over a 24 hour period, OR normal urine output following transplantation that diminished to < 50 cc/H over a 24 hour period OR Creatinine reduction ratio 24 hours after transplantation to pre-transplantation is < 30%.
8. Dry weight ? 100 kg.
9. Women of child bearing potential have a negative pregnancy test prior to transplantation.
10. Women of child bearing potential (including perimenopausal women who have had a menstrual period within 1 year) must agree to use 2 forms of effective birth control regimen (at least one-barrier method) during the 28-day study period. Men must agree to use condoms during the study period; a condom with spermicide is considered a single barrier.
11. In the opinion of the Investigator, the subject is capable of understanding and complying with the protocol.

1. Los pacientes deben firmar el documento de consentimiento informado antes de la realización de cualquier procedimiento relacionado con el estudio, incluyendo el procedimiento de Selección.
2. Hombres y Mujeres ? 18 años de edad.
3. Hayan tenido un trasplanterenaldebido aenfermedad terminal y requieren diálisis crónica.
4. El fármaco del estudio puede administrarsedentro de las 6 a 36 horas después del trasplante.
5. Recibieron riñón del donante tras muerte cardiaca.
6. El riñón DMCcumple con los criterios del centro médico para el trasplante.
7. El aclaramiento de creatinina del riñón trasplantado durante un periodo de recogida de 2 horas es <10 ml/min, O no hay ninguna producción de orina o es <50 cc/h durante un período de 24 horas, O producción normal de orina después del trasplante que disminuyó a <50 cc/h durante un período de 24 horas, O la relación de reducción de creatinina entre las 24 horas después del trasplante y el pre-trasplante es <30%.
8. Peso en vacío ?100kg.
9. Las mujeres en edad fértil han tenido una prueba de embarazo negativa antes del trasplante.
10. Las mujeres en edad fértil (entre ellas mujeres perimenopáusicas que han tenido una menstruación en el último año) deberán estar de acuerdo en utilizar 2 métodos anticonceptivos eficaces (al menos un método de barrera) durante el período de estudio de 28 días. Los hombres deberán estar de acuerdo en usar preservativos durante el período de estudio, un preservativo con espermicida se considera una sola barrera.
11.En opinión del Investigador, el individuo es capaz de entender y cumplir con el protocolo.

E.4

Principal exclusion criteria

1. Mean arterial pressure <40 mmHg or cardiac index <1.8 L/min/m2.
2. Recipient of multiple organ transplantation or scheduled for multiple organ transplantation.
3. Recipient of kidney from a pediatric donor age 10 years or less.
4. Recipient age > 75 years.
5. Patients with ASA 4 or 5
6. Patients with chronic obstructive pulmonary disease (COPD) GOLD IV
7. Has measurable donor-specific antibody or positive cross-match requiring deviation from standard immunosuppressive therapy.
8. Currently participating in or has participated in an investigational drug or medical device study within 30 days or five half-lives, whichever is longer, prior to enrolment into this study.
9. Concurrent sepsis or active bacterial infection.
10. Have an active malignancy or history of solid, metastatic or hematologic malignancy with the exception of basal or squamous cell carcinoma of the skin that has been removed.
11. Women of child bearing potential who is breast feeding.
12. History of positive HIV test.
13. History of rheumatoid arthritis.
14. History of proliferative retinopathy or laser surgery for retinopathy.
15. Subjects who have a penicillin allergy.
16. Subjects who require the cytochrome P450 1A2 (CYP1A2) inhibitors, or are receiving ciprofloxacin and fluvoxamine (Luvox®).
17. Subject is unwilling or unable to comply with the protocol or to cooperate fully with the Investigator or the site personnel.
18. Subject is not deemed medically stable for the study in the opinion of the Investigator or the subject?s primary nephrologist.

1. Presión arterialmedia<40mmHgoíndice cardiaco<1.8L/min/m2.
2. Receptor de trasplante múltiple de órganosoprogramado paratrasplante múltiple de órganos.
3. Receptor de riñón procedente de donante pediátrico edad10años o menos.
4. Edad del receptor >75años.
5. Pacientes con ASA 4 o 5
6. Pacientescon enfermedad pulmonar obstructiva crónica (EPOC) GOLDIV
7. Tiene anticuerpos medibles específicos del donante o un ?cross-match? positivo que requiere desviación de la terapia inmunosupresora estándar.
8. Actualmente participa o ha participado en un estudio de un fármaco en investigación o de un dispositivo médico dentro de los 30 días o cinco vidas medias, lo que sea mayor, antes de la inscripción en el estudio.
9. Sepsis concurrente o infección bacteriana activa
10. Tener una enfermedad maligna activa o antecedentes de tumores malignos sólidos, metastásicos o hematológicos con la excepción de carcinoma de células basales o escamosas de la piel que ha sido eliminado.
11. Mujeres en edad fértil que están amamantando.
12. Historialde prueba positiva de VIH.
13. Historialde artritisreumatoide.
14. Historial deretinopatía proliferativao cirugía con láser para la retinopatía.
15. Pacientes alérgicos a la penicilina.
16. Pacientes que requierenlos inhibidores del citocromo P450 1A2 (CYP1A2),o que están recibiendo ciprofloxacino y fluvoxamina (Luvox®).
17. El paciente no está dispuesto o es incapaz de cumplir con el protocolo o de cooperar plenamente con el Investigador o con el personal del centro.
18. El paciente no se considera médicamente estable para el estudio en opinión del Investigador o del nefrólogo habitual del sujeto.

E.5 End points

E.5.1

Primary end point(s)

Creatinine clearance (CrCl) over time, as assessed by selective 24-hour urine collections from the donor kidney, starting from the first infusion of the study drug, to day 7 post-transplant.

El aclaramiento de creatinina (ACr) en el tiempo, según lo evaluado en las muestras de orina recogidas cada 24-horas desde el trasplante del riñón del donante, a partir de la primera infusión del fármaco del estudio, hasta el día 7 después del trasplante.

E.5.1.1

Timepoint(s) of evaluation of this end point

Every 24 hours from time of first infusion of the study drug to day 7 post-transplant.

Cada 24 horas desde el momento de la primera infusión del fármaco del estudio hasta el día 7 después del trasplante.

E.5.2

Secondary end point(s)

None.

Ninguno

E.5.2.1

Timepoint(s) of evaluation of this end point

- Median time (days) until production of ?1 liter urine over a 24-hour period
- Calculated creatinine clearance at days 14 and 28
- Incidence of delayed graft function (required dialysis due to inadequate renal function) during the first 7 days after transplantation
- Number of dialysis sessions through day 7, 14, and 28
- Mean total daily urine output through day 14
- Daily serum creatinine at days 1 to 7 and at days 1 to 14
- Mean serum creatinine at days 4, 7, 10, 14, and 28
- Length of hospitalization following transplantation
- Results of the 6- and 12-month follow-up on graft survival and function

- Mediana de tiempo (días) hasta la producción de 1 litro de orina en un período de 24 horas
- Aclaramiento de creatinina calculado en los días 14 y 28
- La incidencia de la función retardada del injerto (diálisis necesaria debido a una función renal inadecuada) durante los primeros 7 días después del trasplante
- Número de sesiones de diálisis durante los días 7, 14 y 28
- Media diaria de orina excretada el día 14
- Creatinina sérica diaria en los días 1 a 7 y en los días 1 al 14
- Media de la creatinina sérica los días 4, 7, 10, 14 y 28
- Duración de la hospitalización tras el trasplante
- Resultados relativos a la supervivencia y la función del injerto en el seguimiento a los 6 y 12 meses

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

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

Yes

E.8.4

The trial involves multiple sites in the 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

E.8.6.2

Trial being conducted completely outside of the EEA

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

The end of the study is defined as the last patient?s last visit, i.e. the completion of the 12 month follow up visit by the last patient.

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