Clinical Trials Register

Summary
EudraCT Number:	2018-001162-42
Sponsor's Protocol Code Number:	AIFA-2016-02364896
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2019-03-14
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2018-001162-42

A.3

Full title of the trial

A phase 2 open-label study to evaluate the efficacy of allogeneic human cord blood-derived mesenchymal stromal cells in maintaining remission after immunosuppressive therapy withdrawal in pediatric patients with steroid-dependent nephrotic syndrome

Studio di fase 2 per la valutazione dell'efficacia delle cellule mesenchimali stromali di origine cordonale nel mantenimento della remissione dopo sospensione della terapia immunosoppressiva in pazienti pediatrici affetti da sindrome nefrosica cortico-dipendente.

A.3.1

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

A phase 2 study to evaluate the efficacy of allogeneic human cord blood-derived mesenchymal stromal cells in pediatric patients with steroid-dependent nephrotic syndrome in maintaining remission after immunosuppressive therapy withdrawal

Studio di fase 2 per valutare l’efficacia delle cellule mesenchimali allogeniche ottenute da sangue cordonale nei pazienti pediatrici affetti da sindrome nefrosica cortico-dipendente in remissione con terapia immunosoppressiva

A.3.2

Name or abbreviated title of the trial where available

Reduce immunosuppression with Atmp in NS ChildrEn - RACE

Riduzione della terapia immunosoppressiva con Atmp in bambini con SN - RACE

A.4.1

Sponsor's protocol code number

AIFA-2016-02364896

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	FONDAZIONE IRCCS CA' GRANDA OSPEDALE MAGGIORE POLICLINICO
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
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	FONDAZIONE IRCCS CA' GRANDA OSPEDALE MAGGIORE POLICLINICO
B.5.2	Functional name of contact point	U.O.C. Nefrologia, Dialisi e Trapia
B.5.3	Address:
B.5.3.1	Street Address	Via della Commenda, 9
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20122
B.5.3.4	Country	Italy
B.5.4	Telephone number	0255032336
B.5.5	Fax number	0255032451
B.5.6	E-mail	giovanni.montini@unimi.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	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	Cellule mesenchimali stromali di origine cordonale (CB-MSC) per uso allogenico)
D.3.2	Product code	CF-CB-MSC
D.3.4	Pharmaceutical form	Suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	CF-CB-MSC
D.3.10	Strength
D.3.10.1	Concentration unit	Other
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	1000000 to 3000000
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)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	Yes
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Steroid dependent nephrotic syndrome

Sindrome nefrosica cortico-dipendente

E.1.1.1

Medical condition in easily understood language

Steroid dependent nephrotic syndrome

Sindrome nefrosica dipendente da farmaci steroidei

E.1.1.2

Therapeutic area

Diseases [C] - Symptoms and general pathology [C23]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	SOC
E.1.2	Classification code	10038359
E.1.2	Term	Renal and urinary disorders
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

To evaluate whether CF-CB-MSC therapy is able to prevent NS recurrence for at least 6 months after complete withdrawal of immunosuppressive treatment in children with SDNS.

Valutare se la terapia con le cellule mesenchimali da sangue di cordone ombelicale espanse in vitro (CF-CB-MSC) è capace di prevenire la recidiva di malattia per almeno 6 mesi dopo la sospensione completa del trattamento immunosoppressivo nei bambini con sindrome nefrosica steroide-dipendente.

E.2.2

Secondary objectives of the trial

To assess:
- whether CB-MSC therapy may reduce the need for steroids and other immunosuppressive agents to prevent and treat further disease relapses;
- the time to recurrence of proteinuria after treatment;
- the dosage and time schedule of CF-CB-MSC treatments needed to maintain remission of proteinuria after immunosuppressive treatment withdrawal;
- the treatment safety profile;
- the regression of related toxicities, such as hypertension, impaired glucose tolerance and dyslipidemia.

Valutare:
- se la terapia con CB-MSC possa ridurre la necessità di farmaci steroidei e di altri agenti immunosoppressori per prevenire e trattare eventuali recidive;
- il tempo di ricomparsa di proteinuria dopo trattamento;
- il dosaggio delle CF-Cb-MSC e schema di trattamento necessari per il mantenimento della remissione della proteinuria dopo sospensione del trattamento con immunosoppressori;
- il profilo di sicurezza del trattamento;
la regressione delle tossicità correlate, come ipertensione, ridotta tolleranza al glucosio, dislipidemia.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age between 3 and 18 years;
2. Clinical diagnosis of SDNS;
3. Disease remission maintained by chronic therapy (at least 6 months) with either:
‐ Use of a combination of 2 or more immunosuppressive drugs
‐ use of 1 of the calcineurin inhibitors (Cyclosporin or Tacrolimus);
4. Absence of proteinuria (PrU/CrU < 0.2 mg/mg) for at least 1 month;
5. eGFR greater than or equal to 70 ml/min/1.73 m^2;
6. Written informed consent from parents or guardians and the child when possible.

1. Età compresa tra i 3 e i 18 anni;
2. Diagnosi clinica di SDNS;
3. Remissione mantenuta con terapia cronica (da almeno 6 mesi) con le seguenti terapie:
‐ Utilizzo della combinazione di 2 o più farmaci immunosoppressivi;
‐ Utilizzo di 1 inibitore delle calcineurine (ciclosporina, o tacrolimus);
4. Assenza di proteinuria (PrU/CrU< 0.2 mg/mg) per almeno 1 mese;
5. eGFR maggiore o uguale a 70 ml/min/1.73 m^2;
6. Consenso informato scritto per i genitori o il tutore legale e assenso del bambino quando possibile.

E.4

Principal exclusion criteria

1. Age < 3 years or ≥ 19 years;
2. Resistant/refractory NS;
3. Presence of genetic mutations associated with NS;
4. eGFR less than 70 ml/min/1.73m^2;
5. Thrombophilic condition;
6. Pregnancy or lactating;
7. Evidence of an uncooperative attitude;
8. Any evidence that the patient will be unable to complete the trial follow-up.

1. Età < 3 anni o ≥ 19 anni;
2. NS resistente/refrattaria;
3. Presenza di mutazioni genetiche associate alla NS;
4. eGFR minore di 70 ml/min/1.73 m^2;
5. Stato trombofilico
6. Gravidanza o allattamento;
7. Evidenza di comportamento non collaborativo;
8. Qualsiasi evidenza che il paziente non sia in grado di completare il follow-up dello studio.

E.5 End points

E.5.1

Primary end point(s)

The percentage of patients without NS recurrence after complete withdrawal of immunosuppressive treatment for at least 6 months.

Percentuale di bambini senza recidiva della NS dopo sospensione completa del trattamento immunosoppressivo per almeno 6 mesi.

E.5.1.1

Timepoint(s) of evaluation of this end point

6 months

6 mesi

E.5.2

Secondary end point(s)

- The percentage of adverse events;
- The time to recurrence of nephrotic syndrome;
- The percentage of participants achieving a reduction in the immunosuppressive therapy;
- The dose of immunosuppressive therapy to prevent further NS relapses;
- Quality of life.

- Percentuale di eventi avversi;
- Tempo di recidiva alla sindrome nefrosica;
- Percentuale di soggetti che raggiungono una riduzione della terapia immunosoppressiva;
- Dosaggio di terapia immunosoppressiva per prevenire ulteriori recidive di NS;
- Qualità di vita

E.5.2.1

Timepoint(s) of evaluation of this end point

6 months

6 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

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Information not present in EudraCT

E.8.1.6

Cross over

Information not present in EudraCT

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

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

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

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)

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)

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

Yes

F.3.3.2

Women of child-bearing potential using contraception

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

Yes

F.3.3.7.1

Details of other specific vulnerable populations

Patients <18 years

Pazienti < 18 anni

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

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 will continue to be followed-up according to routine clinical practice. In case of relapse patients will be treated with the usual treatment of relapses: oral Prednisone at a dose of 60 mg/m^2 up to 5 days after the remission. Thereafter, a single dose of 40 mg/m^2 on alternate-day will be continued for 4 weeks.

I pazienti proseguiranno un follow-up clinico standard previsto per la patologia di base. In caso di recidive della patologia di base, queste verranno trattate secondo terapia standard con prednisone 60 mg/mq fino a 5 giorni dopo la avvenuta remissione, quindi 40 mg/mq a giorni alterni per ulteriori 4 settimane.

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

2018-08-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-03-27

P. End of Trial
P.	End of Trial Status	Ongoing

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