Clinical Trials Register

Summary
EudraCT Number:	2015-001750-15
Sponsor's Protocol Code Number:	1293.10
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:	2020-11-05
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

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

Studio clinico in doppio cieco, randomizzato, controllato verso placebo per valutare l’effetto di BI 655064, somministrato come iniezione sub-cutanea, sulla risposta renale dopo un anno di trattamento in pazienti con nefrite lupica attiva

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

Efficacia e sicurezza di BI 655064 in pazienti con nefrite lupica attiva

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.5.4

Other Identifiers

Name:

Number:

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 ITALIA S.P.A.
B.1.3.4	Country	Italy
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 Italia SpA
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Boehringer Ingelheim
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	00498002430127
B.5.5	Fax number	00498008217119
B.5.6	E-mail	clintriage.rdg@boehringeringelheim.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 180 mg (180 mg/ml)]
D.3.4	Pharmaceutical form	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.3.9.2	Current sponsor code	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)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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 anta. ther. 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 120 mg (180 mg/ml)]
D.3.4	Pharmaceutical form	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.3.9.2	Current sponsor code	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)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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 anta. ther. 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
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	Solution for injection
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

nefrite lupica attiva

E.1.1.1

Medical condition in easily understood language

Lupus nephritis

nefrite lupica attiva

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	21.1
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

caratterizzare la relazione dose-risposta, identificare la dose target ed indagare la sicurezza, la tollerabilità e l’efficacia di tre dosi di BI 655064 somministrato in sottocute per 52 settimane in pazienti con nefrite lupica.

E.2.2

Secondary objectives of the trial

assess the efficacy at 6 months

Valutare l'efficacia a 6 mesi

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 reliable methods of birth
control, one of which must be highly effective. Highly effective method,
per ICH M3 (R2) is a method that result in a low failure rate of less than
1% per year when used consistently and correctly. The reliable
contraception should be used before starting MMF therapy and the study
drug, during the treatment and until 50 days 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 or a positive antinuclear antibody (ANA) 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 >= 1) at screening
Signed and dated written informed consent

- Maschi e femmine. Le femmine potenzialmente fertili devono essere disponibili e capaci (secondo il giudizio dello sperimentatore) di usare simultaneamente due metodi contraccettivi, di cui uno altamente efficace secondo le linee guida ICH M3 (R2), che risulta in un basso tasso di fallimento, ad esempio meno dell’1% annuo, quando usato coerentemente e correttamente. La contraccezione affidabile deve essere usata prima di iniziare la terapia con micofenolato (MMF) ed il farmaco in studio, durante il trattamento e per almeno 50 giorni dopo l’interruzione del MMF e del farmaco in studio. La lista dei metodi contraccettivi sarà inclusa nell’informativa paziente. I maschi sessualmente attivi devono essere disponibili ad usare il preservativo durante la terapia con MMF e per almeno 90 giorni dopo l’interruzione del MMF.
- Età di18-70 anni compresi alla Visita 1
- Diagnosi di lupus sistemico eritematoso secondo i criteri ACR 1997, almeno quattro criteri devono essere documentati, uno dei quali deve essere la positività agli anticorpi anti-dsDNA o agli anticorpi anti nucleo (ANA) allo screening oppure intorno al momento d’inizio della terapia d’induzione
- Nefrite lupica classe III o IV (secondo la classificazione ISN/RPS 2003), attiva o cronica/attiva, con associazione della classe V permessa, comprovata dalla biopsia renale entro i tre mesi precedenti lo screening o durante lo screening nel caso in cui la terapia d’induzione per la nefrite lupica non sia stata ancora iniziata
- Patologia renale attiva evidenziata dalla proteinuria >= 1.0 g/day (Uprot/Ucrea >= 1) allo screening
- Consenso informato, firmato e datato in conformità alle GCP e alle normative locali prima della partecipazione alla sperimentazione

E.4

Principal exclusion criteria

clinically significant current other renal disease
GFR<30ml/min/1.73m²
Dialysis within 12m of screening
Antiphospholipid syndrom defined as positive antiphospholipid
antibodies and either history of any thrombotic event and or history of
miscarriage.
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
Any induction therapy for LN within the last 6 months prior to
randomisation except induction with MMF and high dose steroids tarted
within 6 weeks prior to randomisation. If a higher dose of iv steroids is
considered necessary by the investigator a total dose of up to 3g is
acceptable
Treatment with any biologic B-cell depleting therapy (e.g. anti-CD20,
anti-CD22) within 12 months prior to randomisation
Treatment with Belimumab or other anti BLyS: when used for treatment
of non-renal SLE 3 months or 5 half lives whichever is longer, prior to
randomisation ; when used for treatment of Lupus nephrits: 12 months
prior to randomisation
Treatment with abatacept within 12 months prior to randomisation
Treatment with tacrolimus or cyclosporin within 4 weeks prior to
randomisation
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 and/or known
hypersensitivity to any constituents of the study drug
Live vaccination within 6 weeks before randomisation
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
Significant central nervous system symptoms related to SLE based on
investigator assessment

- Altra patologia renale attiva clinicamente significativa, secondo il giudizio dello sperimentatore. Ad esempio: glomerulonefrite post infezione, pielonefrite, nefrite interstiziale, glomerulosclerosi.
- GFR < 30 mL/min/1.73m2 allo screening
- Dialisi nei 12 mesi precedenti lo screening
- Sindrome da antifosfolipidi, caratterizzata da una storia di qualsiasi episodio di trombosi e anticorpi antifosfolipidi positivi e/o storia di qualsiasi evento trombotico o la storia di aborto spontaneo
- Diabete mellito se poco controllato secondo lo sperimentatore, oppure nota retinopatia diabetica o nefropatia diabetica
- Attiva o pregressa condizione clinica significativa, diversa dal lupus, o evidenze dell’esame obiettivo (incluso segni vitali ed ECG) che, secondo lo sperimentatore, potrebbero mettere a rischio la sicurezza del paziente oppure compromettere la qualità dei dati. Questo criterio fornisce la possibilità di escludere la partecipazione del paziente sulla base del giudizio clinico anche se gli altri criteri di eleggibilità sono rispettati
- Relativamente ai trattamenti precedenti:
1. Qualsiasi terapia d’induzione per la nefrite lupica nei 6 mesi precedenti la randomizzazione tranne l’induzione con micofelonato e dose alta di steroidi (quantità massima e.v. equivalente a 1.5g di prednisone) iniziata nelle 6 settimane precedenti la randomizzazione. Se una dose più alta è considerata necessaria dal medico dello studio, una dose totale fino a 3g è accettabile.
2. Qualsiasi trattamento biologico che inibisce la stimolazione delle cellule B (ad esempio anti-CD20, anti-CD22) nei 12 mesi precedenti la randomizzazione
3. Il trattamento con Belimumab o altri BLyS anti-: quando viene utilizzato per il trattamento del lupus eritematoso sistemico 3 mesi o 5 emivite a seconda di quale è più lungo, prima della randomizzazione; quando viene utilizzato per il trattamento della nefrite lupica: 12 mesi precedenti la randomizzazione
4. Abatacept nei 12 mesi precedenti la randomizzazione
5. Tracolimus o ciclosporina nelle 4 settimane precedenti la randomizzazione
6. Ciclofosfamide nei 6 mesi precedenti la randomizzazione

Per gli altri criteri, si faccia riferimento alla sinossi in italiano

E.5 End points

E.5.1

Primary end point(s)

1: proportion of patients with complete renal response

1) Primario: proporzione di pazienti con risposta renale completa alla settimana 52

E.5.1.1

Timepoint(s) of evaluation of this end point

1: week 52

1) Alla settimana 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

1) Proporzione di pazienti con risposta renale completa alla settimana 26;
2) Proporzione di pazienti con risposta renale parziale alla settimana 26 ed alla settimana 52;
3) Proporzione di pazienti con risposta renale importante alla settimana 26 ed alla settimana 52;

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

1) Alla settimana 26;
2) Alla settimana 26 ed alla settimana 52;
3) Alla settimana 26 ed alla settimana 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

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

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

Information not present in EudraCT

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

Czechia

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.1.1.1

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:

109

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

I pazienti, con almeno una risposta parziale al trattamento, potrebbero entrare in un trial di estensione

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

2016-08-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-10-27

P. End of Trial
P.	End of Trial Status	Completed

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Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
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