Clinical Trials Register

Summary
EudraCT Number:	2009-016824-29
Sponsor's Protocol Code Number:	1232009
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-02-25
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

Denmark - DHMA

A.2

EudraCT number

2009-016824-29

A.3

Full title of the trial

REsPons på interferon-Alfa hos InterfeRon-β-neutraliserende antistof-positive patienter med multipel sklerose

A.3.2

Name or abbreviated title of the trial where available

REPAIR

A.4.1

Sponsor's protocol code number

1232009

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Dansk Multipel Sclerose Center
B.1.3.4	Country	Denmark
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
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	Multiferon
D.2.1.1.2	Name of the Marketing Authorisation holder	SWEDISH ORPHAN INTERNATIONAL AB
D.2.1.2	Country which granted the Marketing Authorisation	Denmark
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	Solution for injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	HUMAN LEUCOCYTE INTERFERON-ALPHA
D.3.9.1	CAS number	0
D.3.9.2	Current sponsor code	SWEDISH ORPHAN INTERNATIONAL
D.3.9.3	Other descriptive name	HUMAN LEUCOCYTE INTERFERON-ALPHA
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	6000000
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)	Information not present in EudraCT
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	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	Information not present in EudraCT
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	Information not present in EudraCT
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	Rebif
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Serono Europe Limited
D.2.1.2	Country which granted the Marketing Authorisation	Denmark
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	Solution for injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	INTERFERON BETA-1A
D.3.9.1	CAS number	220581-49-7
D.3.9.2	Current sponsor code	Merck Serono
D.3.9.3	Other descriptive name	INTERFERON BETA-1A
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	22 to 44
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)	Information not present in EudraCT
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	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	Information not present in EudraCT
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	Information not present in EudraCT
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: 3
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	Betaferon
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer Schering Pharma AG
D.2.1.2	Country which granted the Marketing Authorisation	Denmark
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	Powder and solvent for solution for injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	INTERFERON BETA-1B
D.3.9.1	CAS number	145155-23-3
D.3.9.2	Current sponsor code	Bayer
D.3.9.3	Other descriptive name	INTERFERON BETA-1B
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	8000000
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)	Information not present in EudraCT
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	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	Information not present in EudraCT
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	Information not present in EudraCT
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

Multiple Sclerosis

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	12.1
E.1.2	Level	PT
E.1.2	Classification code	10063399
E.1.2	Term	Relapsing-remitting multiple sclerosis

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Formål med forsøget er at undersøge, om patienter med MS, som har udviklet neutraliserende antistoffer under behandling med interferon-beta og som følge heraf har mistet det biologiske respons på interferon-beta målt ved mRNA MxA, kan opnå et fuldt mRNA MxA respons efter injektion med interferon-alpha (Multiferon). Et fuldt biologisk respons på interferon-alpha vil medføre, at patienterne vil kunne fortsætte behandlingen med et type I interferon i form af interferon-alpha i stedet for at skifte til en anden klasse af medicin mod MS.

E.2.2

Secondary objectives of the trial

De sekundære formål er at undersøge:
In vivo-responset på IFN-α af fire andre kendte IFN--responsmarkører: interleukin-10 (IL10), tumornekrosefaktor-relateret apoptoseinducerende ligand (TRAIL), IFN-α-inducerbart protein 27 (IFI27) og kemokinet CXCL10 på mRNA-niveau.
Ændringen i NAb-koncentration efter en injektion med IFN-α sammenlignet med NAb-koncentrationen ved baselinebesøget.
Gen-induktion på Affymetrix-chips efter en injektion med IFN-α sammenlignet med en tidligere undersøgt gen-induktion på Affymetrix-chips efter en injektion med IFN-β i en kontrolgruppe bestående af NAb-negative MS-patienter.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Forsøgspersonen skal have afgivet et skriftligt, informeret samtykke før nogen forsøgsrelaterede aktiviteter.
Forsøgspersonen skal være i alderen 18-55 år (inklusive).
Forsøgspersonen skal have MS i henhold til McDonalds kriterier.
Forsøgspersonen skal have neurologisk status svarende 5,5 eller herunder på EDSS skalaen.
Forsøgspersonen skal have været behandlet med et IFN-β-præparat i mindst 12 måneder på et eller andet tidspunkt.
Forsøgspersonen skal have vist sig at være NAb-positiv og uden noget in vivo mRNA MxA-respons inden for de sidste 12 måneder.
Forsøgspersonen skal være forberedt og skal anses for at være i stand til at følge protokollen.

E.4

Principal exclusion criteria

Forsøgspersonen må ikke lide af sygdomme, der kan give symptomer, der minder om MS.
Forsøgspersonen må ikke have fået glatiramer acetat i 3 måneder før screeningsbesøget.
Forsøgspersonen må ikke have fået immunmodulerende eller immunsuppressiv behandling (bortset fra IFN-β eller glatiramer acetat) i 6 måneder før screeningsbesøget.
Forsøgspersonen må ikke have fået mitoxantron, cyclofosfamid, treosulfan, natalizumab, daclizumab, rituximab, alemtuzumab, cladribin eller nogen anden eksperimentel behandling på noget tidspunkt.
Forsøgspersonen må ikke tidligere have fået foretaget en strålebehandling af hele kroppen, strålebehandling af hele lymfesystemet, stamcellebehandling, autolog knoglemarvstransplantation eller allogen knoglemarvstransplantation.
Forsøgspersonen må ikke være blevet behandlet med glukokortikoider eller ATCH senere end 2 måneder før screeningsbesøget.
Forsøgspersonen må ikke være afhængig af alkohol eller stoffer.
Forsøgspersonen må ikke lide af hjerteinsufficiens eller nyreinsufficiens.
Forsøgspersonen må ikke lide af en systemisk sygdom, der kan have indflydelse på forsøgspersonens sikkerhed eller behandlingscompliance.
Forsøgspersonerne kan være mænd eller kvinder. Kvinder i den fødedygtige alder skal være seksuelt inaktive eller anvende en medicinsk acceptabel præventionsmetode. Acceptable metoder omfatter p-piller, implantat, transdermal depotplastre, vaginalring eller depotinjektion). I visse tilfælde kan steril fast partner eller en dobbeltbarrieremetode (kondom eller spiral med sæddræbende creme) findes acceptabelt.Der foretages graviditetstest ved screeningsbesøget).
Forsøgspersonen må ikke have en kendt eller formodet allergi over for IFN-α.
Forsøgspersonen må ikke have deltaget i noget andet forsøg i 3 måneder før screeningsbesøget.

E.5 End points

E.5.1

Primary end point(s)

In vivo mRNA MxA-respons efter en injektion med IFN-α sammenlignet med in vivo mRNA MxA-responset efter en injektion med IFN-β efter besøget ved screenings-/baselinebesøget.

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

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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.8.3

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.8.5

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

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

Forsøget slutter med sidste besøg af den sidste patient

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	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	No
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	10
F.4.2	For a multinational trial
F.4.2.1	In the EEA	10
F.4.2.2	In the whole clinical trial	10

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

2010-04-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-03-11

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2011-06-07

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