Clinical Trials Register

Summary
EudraCT Number:	2015-000624-28
Sponsor's Protocol Code Number:	OFA2
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

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

2015-000624-28

A.3

Full title of the trial

Ofatumumab versus Rituximab in children with steroid and calcineurin inhibitor-dependent idiopatic nephrotic syndrome: an open-label, randomized, controlled, superiority trial.

A.3.1

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

Ofatumumab versus Rituximab in treatment of children with steroid and calcineurin inhibitor-dependent idiopatic nephrotic syndrome:

Confronto tra ofatumumab e rituximab nella terapia della sindrome nefrosica idiopatica dipendente da cortisone e inibitori delle calcineurine

A.3.2

Name or abbreviated title of the trial where available

Ofatumumab versus Rituximab in treatment of steroid dependent INS

Ofatumumab verso Rituximab nel trattamento della sindrome nefrosica cortico dipendente

A.4.1

Sponsor's protocol code number

OFA2

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	IRCCS ISTITUTO GIANNINA GASLINI
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Fondazione Malattie Renali del Bambino - Onlus
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	IRCCS G,Gaslini
B.5.2	Functional name of contact point	UOSD Epidemiologia, biostatistica e
B.5.3	Address:
B.5.3.1	Street Address	Via Gaslini 5
B.5.3.2	Town/ city	Genova
B.5.3.3	Post code	16147
B.5.3.4	Country	Italy
B.5.4	Telephone number	01056363462
B.5.5	Fax number	0108981116
B.5.6	E-mail	comitatoetico@ospedale-gaslini.ge.it

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	Yes
D.2.1.1.1	Trade name	ARZERRA - 100 MG - CONCENTRATO PER SOLUZIONE PER INFUSIONE - USO ENDOVENOSO - FLACONE(VETRO) - 5 ML(20MG/ML) 3 FLACONI
D.2.1.1.2	Name of the Marketing Authorisation holder	GLAXO GROUP LIMITED
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	ofatumumab
D.3.2	Product code	ofatumumab
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 use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Ofatumumab
D.3.9.1	CAS number	679818-59-8
D.3.9.2	Current sponsor code	Ofatumumab
D.3.9.3	Other descriptive name	Ofatumumab
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	20
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	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	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.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Yes
D.2.1.1.1	Trade name	MABTHERA - 1 FIALA 500 MG 50 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	ROCHE REGISTRATION LIMITED
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	rituximab
D.3.2	Product code	rituximab
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 use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	RITUXIMAB
D.3.9.1	CAS number	174722-31-7
D.3.9.2	Current sponsor code	RITUXIMAB
D.3.9.3	Other descriptive name	RITUXIMAB
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	10
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)	Yes
	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	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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

steroid and calcineurin inhibitor-dependent idiopatic nephrotic syndrome

Sindrome nefrosica idiopatica dipendente da terapia con cortisone ed inibitori delle calcineurine

E.1.1.1

Medical condition in easily understood language

standard therapy dependent idiopatic nephrotic syndrome

Sindrome nefrosica dipendente da terapia standard

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	10029164
E.1.2	Term	Nephrotic syndrome
E.1.2	System Organ Class	10038359 - Renal and urinary disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

test whether Ofatumumab is superior to Rituximab in maintaining oral drug-free disease remission (complete or partial remission) at 12 months

testare se Ofatumumab sia superiore a Rituximab nel mantenimento di una remissione di malattia (completa o parziale) senza l¿utilizzo di farmaci per os a 12 mesi nei bambini affetti da INS dipendente da terapia steroidea e con CNI

E.2.2

Secondary objectives of the trial

test whether Ofatumumab is superior to Rituximab in reduce the risk of relapse in a longer follow-up of 24 months in children with steroid and CNI-dependent INS

testare se Ofatumumab sia superiore a Rituximab nella riduzione del rischio di recidiva in un periodo di follow up di 24 mesi nei bambini affetti da INS dipendente da terapia steroidea e con CNI.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-To be in complete disease remission
-Drug dependence: remission has to be maintained with both steroids and CNI
steroid dependence is defined by two consecutive relapses during corticosteroid therapy or within 14 days of ceasing therapy.
CNI (cyclosporine/tacrolimus) dependence is defined by presence of relapse at discontinuation.
-Ability to provide consent and assent: parents’/guardian’s written informed consent, and child’s assent given before any study-related procedure not part of the subject’s normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to his or her future medical care.
-Age between 2 and 18 years

-Remissione completa di malattia.
-Dipendenza dai farmaci: la remissione di malattia deve essere mantenuta con entrambe le terapie, steroidea e con CNI.
La corticodipendenza è definita come la presenza di due recidive consecutive in corso di terapia steroidea o entro 14 giorni dalla sua sospensione. La dipendenza da CNI (tacrolimus/ciclosporina) è definitica come la presenza di relapse in seguito alla sospensione.
-Età compresa tra 2 e 18 anni.
-Capacità di fornire un consenso/assenso: il consenso informato del genitore/tutore e l’assenso del bambino devono essere ottenuti prima di intraprendere qualsiasi procedura dello studio che non sia parte della normale assistenza del paziente e con la consapevolezza che tale consenso possa essere ritirato in qualsiasi momento, senza che ciò comporti un pregiudizio in merito al trattamento futuro del soggetto

E.4

Principal exclusion criteria

-Positivity to autoimmunity tests (ANA, nDNA, ANCA)
-Reduction of C3 levels.
-eGFR<90/ml/min/1,73 m2 valuated according to revised Bedside Schwartz Formula for patients between 2 and 17 years and with CKD-EPI Creatinine 2009 Equation for 18 years old patients.
-Pregnancy
-Neoplasm
-Infections: previous or actual HBV (with HBeAb positivity) or HCV infection
-CD20 B lymphocytes count <2,5%
-Treatment with Rituximab or cyclophosphamide in the last 6 months
-Homozygous or heterozygous mutations of podocitary genes, commonly involved in the etiology of INS (NPHS1, NPHS2, NPHS3, NPHS6, WT1, COQ2, COQ6, MYO1E, SMARCAL1, LAMB2, SCARB2, CD2AP, TRPC6, ACTN4, INF2, LMX1B, MYH9 )

-Positività a test autoimmuni (ANA, ds DNA, ANCA)
-Riduzione dei livelli plasmatici della componente C3 del complemento.
-Filtrato glomerulare (estimated glomerular filtration rate, eGFR) < 90 ml/min/1.73 m2 calcolato secondo la Formula di Schwartz per i pazienti di età compresa tra 2 e 17 anni e secondo l’equazione CKD-EPI Creatinine 2009 per I pazienti di 18 anni.
-Mutazioni in omozigosi o eterozigosi per geni podocitari, comunemente coinvolti nella genesi dell’INS (NPHS1, NPHS2, NPHS3, NPHS6, WT1, COQ2, COQ6, MYO1E, SMARCAL1, LAMB2, SCARB2, CD2AP, TRPC6, ACTN4, INF2, LMX1B, MYH9).
-Gravidanza
-Neoplasie
-Infezioni: infezione pregressa o attuale da HBV (con positività per anticorpi anti HBe) o HCV.
-Conta dei linfociti B CD20 positivi <2,5%
-Trattamento con Rituximab o ciclofosfamide negli ultimi 6 mesi.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoints will be risk of relapse at 12 months without steroid or calcineurin-inhibitors.

rischio di recidiva a 12 mesi, senza la somministrazione di steroide e CNI.

E.5.1.1

Timepoint(s) of evaluation of this end point

12 months

12 mesi

E.5.2

Secondary end point(s)

The secondary endpoint will be the amount of steroids required to maintain complete disease remission at 6 and 24 months after Ofatumumab or Rituximab pulse.; evaluation of circulating cell populations as
biomarkers and predictors of response to treatment with anti-CD20.

quantit¿ di steroide necessaria per mantenere la remissione complete a 6 e 24 mesi dalla somministrazione di Ofatumumab o Rituximab. ; valutazione delle popolazioni cellulari circolanti come
biomarkers o predittori della risposta al trattamento con anti CD20.

E.5.2.1

Timepoint(s) of evaluation of this end point

6 months - 24 months ; 6-24 months

6 mesi - 24 mesi; 6 -24 mesi

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

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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)

Yes

E.8.2.2

Placebo

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.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

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

Information not present in EudraCT

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

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

Yes

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

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)

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

patients less than 6 years old

minori di anni 6

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

140

F.4.2

For a multinational trial

F.4.2.1

In the EEA

140

F.4.2.2

In the whole clinical trial

140

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)

steroid therapy in case of relapse - continuation of normal clinical practice

terapia steroidea in caso di recidiva - proseguimento normale pratica clinica

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

2015-05-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

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

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