Clinical Trials Register

Summary
EudraCT Number:	2015-001750-15
Sponsor's Protocol Code Number:	1293.10
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-03-04
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

Spain - AEMPS

A.2

EudraCT number

2015-001750-15

A.3

Full title of the trial

A double-blind, randomised, placebo-controlled trial evaluating the effect of BI 655064 administered as sub-cutaneous injections, on renal response after one year treatment in patients with lupus nephritis

Estudio doble ciego, aleatorizado y controlado con placebo para evaluar el efecto de BI 655064, administrado en forma de inyecciones subcutáneas, en la respuesta renal después de un año de tratamiento en pacientes con nefritis lúpica activa.

A.3.1

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

Efficacy and safety of BI 655064 in patients with Lupus Nephritis

Eficacia y seguridad de BI 655064 en pacientes con nefritis lúpica

A.3.2

Name or abbreviated title of the trial where available

POC in lupus nephrits

A.4.1

Sponsor's protocol code number

1293.10

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	Boehringer Ingelheim España, S.A.
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	Boehringer Ingelheim España, S.A.
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	Boehringer Ingelheim Pharma GmbH & Co. KG
B.5.2	Functional name of contact point	QRPE PSC CT Information Disclosure
B.5.3	Address:
B.5.3.1	Street Address	Binger Strasse 173
B.5.3.2	Town/ city	Ingelheim am Rhein
B.5.3.3	Post code	55216
B.5.3.4	Country	Germany
B.5.4	Telephone number	+34 934045100
B.5.5	Fax number	+34 934045580
B.5.6	E-mail	clintriage.rdg@boehringer-ingelheim.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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	BI 655064
D.3.2	Product code	BI 655064 120 mg/ml
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
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	Not available
D.3.9.2	Current sponsor code	BI 655064
D.3.9.3	Other descriptive name	BI 655064
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	120
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	humanized non-depleting antagonistic therapeutic antibody
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	BI 655064
D.3.2	Product code	BI 655064 180 mg/ml
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
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	Not available
D.3.9.2	Current sponsor code	BI 655064
D.3.9.3	Other descriptive name	BI 655064
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	180
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	humanized non-depleting antagonistic therapeutic antibody

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 injection in pre-filled syringe
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Lupus Nephritis

Nefritis lúpica

E.1.1.1

Medical condition in easily understood language

Lupus nephritis

Nefritis lúpica

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	18.1
E.1.2	Level	PT
E.1.2	Classification code	10025140
E.1.2	Term	Lupus nephritis
E.1.2	System Organ Class	10038359 - Renal and urinary 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

assess efficacy and safety of one year treatment with three different doses of BI 655064 against placebo as add-on therapy to standard of care (SOC) treatment for active lupus nephritis

Evaluar la eficacia y seguridad tras un año de tratamiento con tres dosis de BI 655064 frente a placebo como terapaia adicional al tratamiento estandar (SOC) para el tratamiento activo de la nefritis lúpica

E.2.2

Secondary objectives of the trial

assess the efficacy at 6 months

evaluar la eficacia a los 6 meses

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

males and females 18-70 years. Women of childbearing potential* must be ready and able to use simultaneously two highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. The contraception should be used before starting MMF therapy and the study drug, during the treatment and until 6 weeks after stopping MMF and the study drug. Sexually active men must be ready to use condoms during treatment with MMF and for at least 90 days after cessation of MMF treatment.
Diagnosis of systemic lupus erythematosus (SLE) by ACR criteria 1997, at least 4 criteria must be documented, one of which must be a positive anti-dsDNA antibody at screening or around time of start of induction therapy
Lupus Nephritis Class III or IV (ISN/RPS 2003 classification) with either active or active/chronic disease, co-existing class V permitted, proven by renal biopsy within 3 months prior to screening or during screening if induction therapy has not yet been started
Active renal disease evidenced by proteinuria >= 1.0 g/day (Uprot/ucrea >= 100 mg/mmol)
Signed and dated written informed consent

-Varones y mujeres de 18 a 70 años de edad. Las mujeres potencialmente fértiles deben querer y poder utilizar simultáneamente dos métodos anticonceptivos altamente eficaces según la directriz M3(R2) de la ICH, es decir aquellos con una tasa de fracaso baja, inferior al 1 %, cuando se utilizan correctamente y de forma sistemática. Los métodos anticonceptivos deben usarse antes de iniciar el tratamiento con MMF y el fármaco en estudio, durante el tratamiento y hasta 6 semanas después de tomar MMF y el fármaco en estudio. Los varones sexualmente activos deben estar dispuestos a utilizar preservativos durante el tratamiento con MMF y como mínimo durante 90 días tras cesar el tratamiento con MMF.
-Diagnóstico de lupus eritematoso sistémico (SLE) mediante los criterios de la ACR de 1997; deben documentarse al menos 4 criterios, uno de los cuales debe ser un resultado positivo en anticuerpos anti-ADN bicatenario (dsDNA) en la selección o alrededor del momento de inicio de la terapia de inducción.
-Nefritis lúpica (LN) de clase III o IV (clasificación ISN/RPS de 2003) con enfermedad activa o enfermedad activa/crónica, con una clase V coexistente permitida, demostrada mediante biopsia renal en los 3 meses previos a la selección o durante la selección en el caso de que no se haya iniciado todavía el tratamiento de inducción para la LN.
-Nefropatía activa evidenciada mediante proteinuria ? 1,0 g/día (Uprot/Ucrea ? 100 mg/mmol).
-Consentimiento informado fechado y firmado.

E.4

Principal exclusion criteria

clinically significant current other renal disease
GFR<30ml/min/1.73m²
Acute presence of Oliguria (<500 mL/day)
dialysis within 12m of screening
Antiphospholipid syndrom
diabetes mellitus poorly controlled or known diabethic retinopathy or nephropathy
Evidence of current or previous clinically significant disease, medical condition or finding in the medical examination that in the investigator's opinion would compromise the safety of the patient or the quality of the data
Live vaccination within 6 weeks before randomisation
Any induction therapy for LN within the last 6 months prior to randomisation except induction with MMF and high dose steroids tarted within 4 weeks prior to randomisation
Treatment with any biologic B-cell depleting therapy (e.g. anti-CD20, anti-CD22, anti-BLyS) within 12 months prior to screening
Treatment with abatacept within 12 months prior to screening
Treatment with tacrolimus or cyclosporin within 4 weeks prior to screening
Treatment with cyclophosphamid within 6 months prior to randomisation
Treatment with investigational drug within 6 months or 5 half-lives, whichever is greater before randomisation
Contraindication for MMF or corticosteroids
Chronic or relevant acute infections, including but not limited to HIV, Hepatitis B and C and tuberculosis (including a history of clinical TB and/or a positive QuantiFERON TB-Gold test
Any active or suspected malignancy or history of documented malignancy within the last 5 years before screening, except appropriately treated carcinoma in situ and treated basal cell carcinoma.
Patients unable to comply with the protocol in the investigator¿s opinion.
Alcohol abuse in the opinion of the investigator or active drug abuse .
Women who are pregnant, nursing, or who plan to become pregnant while in the trial
Impaired hepatic function, defined as serum AST/ALT, bilirubin or alkaline phosphatase levels > 2 x ULN

Otras enfermedades renales actuales clínicamente significativas
GFR < 30 ml/min/1,73 m2 en la selección.
Presencia aguda de oliguria (< 500 ml/día).
Diálisis en los 12 meses anteriores a la selección.
Síndrome antifosfolipídico
Diabetes mellitus mal controlada según el investigador o retinopatía diabética o nefropatía diabética diagnosticadas.
Signos de enfermedad actual o previa clínicamente significativa, enfermedad o resultados en la exploración física que según el criterio del investigador, podrían poner en peligro la seguridad del paciente o la calidad de los datos.
Vacunación en los 6 meses anteriores a la aleatorización
Cualquier tratamiento de inducción para la LN en los últimos 6 meses previos a la aleatorización, excepto la inducción con MMF y dosis altas de esteroides (cantidad máxima de esteroides i.v. de 1,5 g de prednisona equivalente), iniciado en las 4 semanas previas a la aleatorización.
Tratamiento con cualquier tratamiento biológico reductor de linfocitos B (p. ej., anti-CD20, anti-CD22, anti-BLyS) en los 12 meses previos a la aleatorización.
Tratamiento con abatacept en los 12 meses previos a la aleatorización.
Tratamiento con tacrolimús o ciclosporina en las 4 semanas previas a la aleatorización.
Tratamiento con ciclofosfamida en los 6 meses previos a la aleatorización.
Tratamiento con un fármaco en investigación en los 6 meses o 5 semividas, lo que sea mayor, antes de la aleatorización.
Contraindicación a micofenolato mofetilo o corticosteroides.
Infecciones agudas o crónicas incluidas entre otras HIV, hepatitis B o C y tuberculosis (incluyendo TB activa actual o latente en la historia clínica, o tener un resultado positivo en la prueba QuantiFERON-TB Gold, cualquier neoplasia maligna activa o sospechada o diagnóstico confirmado de neoplasia maligna en los últimos 5 años previos a la selección, excepto en el caso del carcinoma in situ tratado de forma adecuada y los carcinomas epidermoides y basocelulares tratados.
Pacientes que no pueden cumplir con el protocolo en opinión del investigador.
Abuso de alcohol o drogas en opinión del investigador.
Mujeres embarazadas, en periodo de lactancia o que prevean quedarse embarazadas durante el periodo del estudio.
Alteración de la función hepática, definida como unos niveles séricos de AST/ALT, bilirrubina o fosfatasa alcalina > 2 veces el ULN.

E.5 End points

E.5.1

Primary end point(s)

1: proportion of patients with complete renal response

E.5.1.1

Timepoint(s) of evaluation of this end point

1: week 52

E.5.2

Secondary end point(s)

1: proportion of patients with complete renal response

2: proportion of patients with partial renal response

3: proportion of patients with major renal response

E.5.2.1

Timepoint(s) of evaluation of this end point

1: week 26

2: week 26 and 52

3: week 26 and 52

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

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

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.8.5.1

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

Austria

Canada

Czech Republic

France

Germany

Greece

Hong Kong

Italy

Japan

Korea, Republic of

Poland

Portugal

Singapore

Spain

Thailand

Turkey

United Kingdom

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

160

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)

patients with at least partial response could enter an extension trial

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

2016-05-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-05-12

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-08-18

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IMP with orphan designation in the indication
Orphan Designation Number:
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