Clinical Trials Register

Summary
EudraCT Number:	2017-005129-18
Sponsor's Protocol Code Number:	PROMISE
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:	2018-03-26
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

2017-005129-18

A.3

Full title of the trial

Multi-centre, randomised, open label pragmatic trial to compare the effectiveness and safety of interferon beta-1a (IFN-beta-1a) weekly i.m. and glatiramer-acetate (GA) in paediatric patients affected by multiple sclerosis.

Studio pragmatico, multicentrico, randomizzato, in aperto per confrontare l'efficacia e la sicurezza dell'interferone beta-1a (IFN beta-1a) settimanale i.m. e glatiramer-acetato (GA) in pazienti pediatrici affetti da sclerosi multipla

A.3.1

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

Clinical trial to evaluate the effectiveness and safety of IFN beta-1a (IFN beta-1a), injected once a week via intramuscolar (i.m.), and glatiramer-acetate (GA) in children/adolescent patients with multiple sclerosis.

Studio clinico per confrontare efficacia e sicurezza dell'interferone beta-1a (IFN beta-1a), somministrato una volta a settimana nel muscolo, e glatiramer-acetato (GA) in pazienti pediatrici affetti da sclerosi multipla.

A.4.1

Sponsor's protocol code number

PROMISE

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	Università degli Studi Aldo Moro
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	AIFA
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	Università degli Studi Aldo Moro
B.5.2	Functional name of contact point	Lucia Margari
B.5.3	Address:
B.5.3.1	Street Address	Piazza Giulio Cesare, 11
B.5.3.2	Town/ city	Bari
B.5.3.3	Post code	70124
B.5.3.4	Country	Italy
B.5.4	Telephone number	+390805592829
B.5.5	Fax number	+390805595260
B.5.6	E-mail	lucia.margari@uniba.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	Copaxone 40 mg/ml solution for injection, pre-filled syringe
D.2.1.1.2	Name of the Marketing Authorisation holder	Teva Pharmaceuticals Ltd
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.3.4	Pharmaceutical form	Suspension 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	Glatiramer Acetate
D.3.9.1	CAS number	147245-92-9
D.3.9.3	Other descriptive name	GLATIRAMER ACETATE
D.3.9.4	EV Substance Code	SUB13971MIG
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	40
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.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	Yes
D.2.1.1.1	Trade name	AVONEX 30 µg/0,5 ml solution for injection
D.2.1.1.2	Name of the Marketing Authorisation holder	BIOGEN IDEC 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.3.4	Pharmaceutical form	Suspension for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Interferon beta-1a
D.3.9.1	CAS number	145258-61-3
D.3.9.3	Other descriptive name	INTERFERON BETA-1A
D.3.9.4	EV Substance Code	SUB12440MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Relapsing-remitting multiple sclerosis with paediatric onset

Sclerosi multipla ad esordio pediatrico con forma recidivante-remittente (RR)

E.1.1.1

Medical condition in easily understood language

Multiple sclerosis in children and adolescents aged up to 17 years wth relapsing-remitting course

Sclerosi multipla ad insorgenza in età inferiore ai 17 anni con forma recidivante-remittente (RR)

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	PT
E.1.2	Classification code	10028245
E.1.2	Term	Multiple sclerosis
E.1.2	System Organ Class	10029205 - Nervous system 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

The main objective of the study is to demonstrate the equivalence of two of injectable drugs (IFN beta 1a 30-mcg im weekly and GA 40 mg s.c. e.o.d.) currently used for the treatment of POMS or the superiority of one of them on MRI and clinical effectiveness outcomes.

Confrontare la sicurezza (frequenza e tipo di eventi avversi) e l'efficacia (attraverso misure di risonanza magnetica) tra l'IFN-beta 1a settimanale i.m. e GA in POMS con forma recidivante-remittente (RR).

E.2.2

Secondary objectives of the trial

Secondary objectives are to compare safety and cost-effectiveness of the two drugs.

Confrontare l'efficacia dell’IFN-beta 1a e GA sul tasso annuale di recidive (ARR), su outcome cognitivi, comportamentali e riportati dal paziente (PRO).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Diagnosis of POMS [23,24]
• Male and female children and adolescents aged between 10 to 17 years included at the time of informed consent (i.e. have not yet had their 18th birthday at randomization);
• Treatment naïve;
• Signed and dated informed consent from parents/legal representative;
• Relapsing remitting course;
• At least one MS relapse during the previous year;
• EDSS score of 0 to 5.5, inclusive
• Subjects of childbearing potential who are sexually active must be willing to practice effective contraception during the study.

• Diagnosi di Sclerosi Multipla Pediatrica (secondo i criteri di Krupp e colleghi 2013);
• Bambini e adolescenti di età compresa tra 10 e 17 anni inclusi al momento della firma del consenso informato (ovvero che non hanno ancora raggiunto il loro diciottesimo compleanno alla randomizzazione)
• Naïve al trattamento;
• Consenso informato datato e firmato dai genitori/rappresentante legale;
• Decorso di malattia recidivante-remittente;
• Presenza di almeno una ricaduta nell’anno precedente;
• Punteggio di disabilità (EDSS score) compreso tra 0 e 5.5 incluso;
• I soggetti in età fertile che sono sessualmente attivi devono essere disposti a praticare contraccettivi efficaci durante lo studio.

E.4

Principal exclusion criteria

• Patients with progressive MS;
• Patients with an active, chronic disease of the immune system other than MS;
• Patients meeting the definition of Acute Disseminated Encephalomyelitis (ADEM);
• Patients with thyroid dysfunction;
• Patients with severe renal insufficiency

• Pazienti con Sclerosi Multipla progressiva;
• Pazienti con una malattia cronica attiva del sistema immunitario diversa dalla SM;
• Pazienti che soddisfano la definizione di Encefalomielite acuta disseminata (ADEM);
• Pazienti con disfunzione tiroidea;
• Pazienti con insufficienza renale grave.

E.5 End points

E.5.1

Primary end point(s)

Proportion of subjects free of new or newly enlarging T2 hyperintense on brain MRI scans at 96 weeks.

Proporzione di soggetti liberi da lesioni T2 iperintense nuove o in allargamento nell’ MRI celebrale a 96 settimane

E.5.1.1

Timepoint(s) of evaluation of this end point

As above

Come sopra

E.5.2

Secondary end point(s)

Efficacy endpoints:
• Annualized relapse rate (ARR) at Weeks 48 and 96;
• Proportion of subjects free of relapse up to Week 96;
• Time to first relapse;
• Time to disability progression defined as 1-point increase of the Expanded Disability Status Scale (EDSS) score confirmed at Week 24;
• Number of new or newly enlarging T2 hyperintense lesions on brain MRI scans at Weeks 48 and 96;
• Number of MRI T1 Gd-enhancing lesions on brain MRI scans at Weeks 48 and 96;
• Change of Symbol Digit Modality test (SDMT) at Weeks 48 and 96;
• Change of Fatigue (FS) score at Weeks 48 and 96;
• Change of QOL (ped QOL) evaluated through Patient Reported Outcomes (PROs) at Weeks 48 and 96;
• Cost-efficacy analyses. An estimate of the cost-effectiveness of the therapeutic regimens under examination.

Safety endpoint:
• Frequency and type of Adverse Events (AEs) during all the study

Endpoint di efficacia:
• Frequenza Annuale di recidive (ARR) a 48 e 96 settimane;
• Proporzione di soggetti liberi da recidive fino alla 96 settimana;
• comparsa della prima recidiva;
• comparsa di progressione della disabilità definita come aumento di 1 punto della Expanded Disability Status Scale (EDSS) confermato alla settimana 24;
• Numero di lesioni T2 iperintense nuove o in allargamento nell’ MRI celebrale alla settimana 48 e 96;
• Numero di lesioni T1 Gd-enhancing alla MRI celebrale alla settimana 48 e 96;
• Variazioni del Symbol Digit Modality Test (SDMT) alla settimana 48 e 96;
• Variazione del Fatigue (FS) score alla settimana 48 e 96;
• Variazione del QOL (ped QOL) valutato attraverso il Patient Reported Outcomes (PROs) alla settimana 48 e 96;
• Analisi costo-efficacia. Una stima del costo-efficacia del regime terapeutico sotto esame.

Endpoint di Sicurezza: Frequenza e tipo di Evento Avverso (AEs) durante tutto lo studio

E.5.2.1

Timepoint(s) of evaluation of this end point

As above

Come sopra

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

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

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

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

Study end is defined as the database lock

La fine dello studio è sancita dalla chiusura del database.

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

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:

142

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:

132

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

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

142

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)

It is possible to continue with the study drug after the clinical study is finished, if patient has received a good benefit in terms of reduced disease recurrence and therefore better clinical control, according to clinical practice.

E’ possibile continuare con il farmaco in studio dopo la conclusione dello studio clinico, se il paziente ha ricevuto beneficio in accordo con le pratiche cliniche ospedaliere.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	Network per la Ricerca Clinica Pediatrica (INCiPiT)
G.4.3.4	Network Country	Italy

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2018-06-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-01-08

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

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