Clinical Trials Register

Summary
EudraCT Number:	2015-000303-21
Sponsor's Protocol Code Number:	BIIT0115
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2015-04-01
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2015-000303-21

A.3

Full title of the trial

A Phase IV, interventional, multicenteR, double-blind, randomized, placebo-controlled study tO explore the onset of efficacy on Magnetic resonance disease activity of BG00012 (dimethyl fumarate) in Patients with relapsing-remitTing Multiple Sclerosis (PROMPT)

Studio di Fase IV interventistico, multicentrico, in doppio cieco, randomizzato, controllato verso placebo, per esplorare l’esordio di efficacia di BG00012 (dimetilfumarato), valutato tramite risonanza magnetica, in pazienti con sclerosi multipla recidivante-remittente (PROMPT)

A.3.1

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

Experimental clinical trial regarding relapsing-remitTing Multiple Sclerosis newly diagnosed patients, not yet treated for the evaluation of the onset, the efficacy and speed of action of the treatment with BG00012

Studio clinico di tipo sperimentale in pazienti affetti da sclerosi multipla recidivante-remittente di nuova diagnosi, non ancora trattati per valutare l'esordio, l'efficacia e la velocità di azione del trattamento con BG00012

A.3.2

Name or abbreviated title of the trial where available

PROMPT

A.4.1

Sponsor's protocol code number

BIIT0115

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	Biogen Idec Italia S.r.l.
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	Biogen Idec Italia S.r.l.
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	GB Pharma Services & Consulting S.r.l. Unipersonale
B.5.2	Functional name of contact point	Clinical Research department
B.5.3	Address:
B.5.3.1	Street Address	via Ferreri, 11
B.5.3.2	Town/ city	Pavia
B.5.3.3	Post code	27100
B.5.3.4	Country	Italy
B.5.4	Telephone number	+39 0382530676
B.5.5	Fax number	+390382302619
B.5.6	E-mail	info@gbpharmaservices.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	Tecfidera®
D.2.1.1.2	Name of the Marketing Authorisation holder	Biogen Idec Ltd
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Tecfidera®
D.3.2	Product code	BG00012
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Dimethyl fumarate
D.3.9.1	CAS number	624-49-7
D.3.9.2	Current sponsor code	BG00012
D.3.9.4	EV Substance Code	SUB13608MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
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	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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule
D.8.4	Route of administration of the placebo	Oral use

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 patients

Pazienti con sclerosi multipla recidivante-remittente

E.1.1.1

Medical condition in easily understood language

relapsing-remitting Multiple Sclerosis patients

Pazienti con sclerosi multipla recidivante-remittente

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	17.1
E.1.2	Level	PT
E.1.2	Classification code	10063399
E.1.2	Term	Relapsing-remitting multiple sclerosis
E.1.2	System Organ Class	10029205 - Nervous system 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

The primary objective of the study is to assess the early efficacy of treatment with BG00012 240 mg BID in the brain of newly diagnosed and naive-to-treatment patients with RRMS.

L’obiettivo primario dello studio è valutare l'esordio e la velocità di efficacia del trattamento con BG00012 240 mg BID, valutata con RMN, in pazienti affetti da SMRR di nuova diagnosi e naive al trattamento.

E.2.2

Secondary objectives of the trial

It will be evaluated the time course of the treatment and safety of BG00012.

Sarà valutato l'andamento nel tempo dell' effetto benefico del trattamento e la sicurezza di BG00012.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

•Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected information in accordance with local subject privacy regulations.
•Patients with RRMS (McDonald criteria, 2010) who do not accept current injectable first-line DMTs
•Age between 18 and 50 years at the time of informed consent.
•MS onset within one year before enrollment (V0)
•≥ 1 Gd+ lesions at a brain MRI scan performed within three months before enrollment(V0).
•No previous disease modifying and/or immunosuppressive treatments for MS
•Must have a baseline EDSS between 0.0 and 5.0, inclusive.
•Women of childbearing potential (i.e. who are not post-menopausal for at least 1 year) and men must practice effective contraception (as defined by the Investigator) during the study and be willing and able to continue contraception for 30 days after their last dose of study treatment.

•Capacità di capire lo scopo e i rischi dello studio e di fornire un consenso datato e firmato e l’autorizzazione al trattamento dei dati sensibili secondo la normativa
•Pazienti con sclerosi multipla recidivante-remittente (RRMS) (secondo i criteri di McDonald, 2010), che non accettano leterapie"disease modifying" di prima linea iniettabili attualmente disponibili
•Età tra i 18 e i 50 anni al momento del consenso informato
•Esordio della malattia nell’anno precedente l' arruolamento (V0)
•≥ 1 lesione Gd+ alla RMN cerebrale eseguita entro tre mesi prima dell' arruolamento (V0)
•Nessun precedente trattamento per la SM (nè di tipo immunosoppressivo nè "disease modifying")
•EDSS basale tra 0.0 e 5.0 (compreso)
•Le donne in età riproduttiva (cioè che non siano in menopausa almeno da 1 anno) e gli uomini dovranno utilizzare un metodo contraccettivo sicuro (a giudizio dello sperimentatore) nel corso dello studio e per almeno 30 giorni dopo l’ultima dose del trattamento in studio.

E.4

Principal exclusion criteria

•Primary progressive, secondary progressive, or progressive relapsing MS, as defined by Lublin and Reingold (Lublin and Reingold 1996)
•Previous disease modifying and/or immunosuppressive treatments for MS, including T-cell or T-cell receptor vaccination, any therapeutic monoclonal antibody, Mitoxantrone, Cyclophosphamide
•Previous treatment with Fumaderm®, dimethyl fumarate or other fumarates
•History of malignancy (except basal cell carcinoma that has been completely excised prior to study enrollment)
•History of severe allergic or anaphylactic reactions or known drug hypersensitivity. Known allergy / hypersensitivity to Gadolinium.
•History of abnormal laboratory results indicative of any significant endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, renal, and/or other major disease that in the opinion of the Investigator would preclude participation in a clinical trial.
•Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection; symptomatic congestive heart failure; unstable angina pectoris; cardiac arrhythmia; serious or acute liver, kidney, or bone marrow dysfunction; uncontrolled diabetes; serious or acute psychiatric illness that would limit compliance with study requirements.
•History of or positive test result at screening for human immunodeficiency virus (HIV). Positive for hepatitis C antibody and/or positive for hepatitis B surface antigen (HBsAg) at screening.
•History of drug or alcohol abuse (as defined by the Investigator) within the 2 years prior to inclusion.
•An MS relapse that has occurred within the 30 days prior to inclusion (screening) AND/OR the subject has not stabilized from a previous relapse prior to inclusion.

•Malattia primaria progressiva, secondaria progressiva o recidivante progressiva, come definito da Lublin and Reingold (Lublin and Reingold 1996)
•Precedente trattamento con Fumaderm®, dimetil-fumarato e/o altri fumarati
•Precedente trattamento Disease-Modifying e/o immunosoppressivo per la sclerosi multipla, inclusi il vaccino contro i linfociti T o i loro recettori, qualunque anticorpo monoclonale terapeutico, mitoxantrone, ciclofosfamide.
•Anamnesi di neoplasie (eccetto il basalioma cutaneo completamente asportato e il carcinoma in situ cervicale sottoposto a conizzazione)
•Anamnesi di gravi reazioni allergiche o anafilattiche o nota ipersensibilità a farmaci o al Gadolinio
•Anamnesi di anomalie nei test di laboratorio che indichino qualunque significativa malattia endocrinologica, ematologica, epatica, immunologica, metabolica, uro-nefrologica, e/o altre malattie maggiori che nell’opinione dello sperimentatore possano precludere la partecipazione ad uno studio clinico.
•Anamnesi di malattie intercorrenti non controllate, incluse, ma non limitate a: infezioni attive o in corso, insufficienza cardiaca congestizia sintomatica, angina pectoris instabile, aritmia cardiaca, disfunzioni serie o acute a livello epatico, renale o midollare, diabete non controllato, malattie psichiatriche serie o in fase acuta, che comportino la non conformità ai requisiti richiesti dallo studio.
•Positività al test per l’HIV o per l’epatite B o C allo screening.
•Anamnesi di abuso di sostanze o alcol nei 2 anni precedenti l’inclusione.
•Recidiva di SM che sia insorta nei 30 giorni precedenti lo screening, E/O mancata stabilizzazione del paziente da una precedente recidiva prima dell’inclusione.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint will be the mean number of cumulative combined unique active (CUA) lesions from week 4 to 24

End point primario: Numero medio di lesioni attive uniche combinate (CUA) cumulative dalla settimana 4 alla settimana 24.

E.5.1.1

Timepoint(s) of evaluation of this end point

From the fourth to the twenty-fourth week

dalla settimana 4 alla settimana 24.

E.5.2

Secondary end point(s)

•Mean number of CUA at 4, 8, 12, 16, 20 and 24 weeks
•New/enlarging T2 lesions at 4, 8, 12, 16, 20 and 24 weeks
•New Gd+ lesions at 4, 8, 12, 16, 20 and 24 weeks
•Mean number of hypointense T1 lesions at 24 weeks
•Safety of BG00012 treatment

- Numero medio di CUA alle settimane 4, 8, 12, 16, 20 e 24.
- LesioniT2nuove/ingrandite alle settimane 4, 8, 12, 16, 20 e 24
- Nuove lesioni captanti gadolinio (Gd+) alle settimane 4, 8, 12, 16, 20 e 24
- Numero medio di lesioni ipointense T1 alla settimana 24
-Sicurezza del trattamento con BG00012

E.5.2.1

Timepoint(s) of evaluation of this end point

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)

E.7.4

Therapeutic use (Phase IV)

Yes

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

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

LVLP

ultima visita per ultimo paziente

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

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:

150

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

150

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)

For patients accessing to the rescue program, alternative drugs will not be supplied by the Sponsor in this study. Treating neurologist may choose among currently available disease modifying treatments (DMTs) according to clinical practice and EMA indication.

Per i pazienti che accedono al rescue program, non verranno forniti dallo sponsor farmaci alternativi. Il Neurologo può scegliere tra i trattamenti modificanti la malattia (DMT) disponibili in queso momento in accordo col la normale pratica clinica e le indicazioni dell'EMA.

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

2015-06-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-05-06

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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