Clinical Trials Register

Summary
EudraCT Number:	2012-003463-22
Sponsor's Protocol Code Number:	AI452-030
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:	2013-01-11
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

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2012-003463-22

A.3

Full title of the trial

MAGNITUDE-A Phase 3 Evaluation of the Safety and Efficacy of
Lambda/RBV/DCV in Treatment Naïve Subjects with Chronic HCV
Infection, who have Underlying Mild or Moderate Hemophilia or Patients
who are Prior Relapsers to Pegylated interferon alfa/RBV.
Revised Protocol 01 Incorporates Amendment 02 and Administrative Letter
01 and 02.

MAGNITUDE- Studio clinico di Fase 3 di valutazione della sicurezza ed efficacia di Lamba/Ribavirina/Daclatasvir in soggetti con infezione cronica da HCV e concomitante emofilia lieve o moderata che sono naive al trattamento o che hanno avuto una recidiva dopo trattamento con Peginterferon alfa-a2/Ribavirina. Protocollo revisionato 01 che include l'emendamento e le lettere amminstrative 01 e 02.

A.3.1

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

A Phase 3 Evaluation of the Safety and Efficacy of Lambda/RBV/DCV in
Treatment Naïve Subjects with Chronic HCV Infection, who have
Underlying Mild or Moderate Hemophilia or Patients who are Prior
Relapsers to Pegylated interferon alfa/RBV

Studio sulla Sicurezza ed Efficacia di lambda/ribavirina/daclatasvir in soggetti con Epatite-C genotipo 1b, 2, 3 e 4 e con emofilia lieve o moderata.

A.4.1

Sponsor's protocol code number

AI452-030

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	BRISTOL-MYERS SQUIBB INTERNATIONAL CORPORATION
B.1.3.4	Country	Belgium
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	Bristol-Myers Squibb International Corporation
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Bristol-Myers Squibb International Corporation
B.5.2	Functional name of contact point	EU Study Start-Up Unit
B.5.3	Address:
B.5.3.1	Street Address	Parc de l'Alliance - Avenue de Finlande, 4
B.5.3.2	Town/ city	Braine-l'Alleud
B.5.3.3	Post code	1420
B.5.3.4	Country	Italy
B.5.6	E-mail	clinical.trials@bms.com

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	Pegylated Interferon Lambda
D.3.2	Product code	BMS-914143
D.3.4	Pharmaceutical form	Solution for injection
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	PEGINTERFERON LAMBDA-1a
D.3.9.1	CAS number	914617-98-4
D.3.9.2	Current sponsor code	BMS-914143
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	400
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	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	Yes
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	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	Daclatasvir
D.3.2	Product code	BMS-790052
D.3.4	Pharmaceutical form	Film-coated tablet
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	daclatasvir
D.3.9.2	Current sponsor code	BMS-790052
D.3.9.3	Other descriptive name	HCV NS5A Replication Co-Factor Inhibitor
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	60
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: 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	RIBASPHERE
D.2.1.1.2	Name of the Marketing Authorisation holder	Three Rivers Pharmaceuticals,
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	Film-coated tablet
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	RIBAVIRIN
D.3.9.1	CAS number	36791-04-5
D.3.9.4	EV Substance Code	SUB10297MIG
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	200
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

Chronic Hepatitis C Virus Infection(Genotype 1b, 2, 3, 4)

Epatite C Cronica (genotipo 1b, 2, 3, e 4)

E.1.1.1

Medical condition in easily understood language

Chronic Hepatitis C

Epatite C Cronica

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10008912
E.1.2	Term	Chronic hepatitis C
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the proportion of subjects who achieve SVR12 (HCV RNA < LLOQ (target not detected) at post-treatment follow-up Week 12 in subjects with GT-1b, -4 and GT-2, -3.

Valutare la percentuale di soggetti che raggiungono la SVR12 (HCV RNA <LLOQ target non rilevato) alla settimana 12 di follow-up post-trattamento nei soggetti con GT-1b, -4 e GT-2, -3.

E.2.2

Secondary objectives of the trial

1. Proportion of subjects who achieve RVR (HCV RNA < LLOQ target not detected at Week 4)
2. Proportion of subjects who achieve cEVR (HCV RNA < LLOQ target not detected at Week 12)
3. Proportion of subjects who have HCV RNA < LLOQ target not detected at Week 24
4. Proportion of subjects with treatment emergent cytopic abnormalities through end of treatment (Week 12 for GT-2, -3 and Week 24 for GT-1b, -4)
5. Proportion of subjects who experience on-treatment IFN-associated symptoms such as flu-like systems or musculosketletal symptoms through Week 12.
6. Proportion of subjects who achieve SVR24 by treatment group
7. Proportion of subjects with SAEs, discontinuation due to AEs and dose reductions through end of follow-up (maximum of 60 weeks for GT-2, -3 and 72 weeks for GT-1b, -4).

1. Proporzione di soggetti che raggiungono la RVR (HCV RNA < LLOQ target non rilevato alla sett 4)
2. Proporzione di soggetti che raggiungono la cEVR (HCV RNA < LLOQ target non rilevato alla sett12).
3. Proporzione di soggetti che hanno HCV RNA < LLOQ target non rilevato alla sett 24
4. Proporzione di soggetti con anomalie citopeniche derivate dal trattamento fino alla fine del trattamento (sett 12 per GT-2. GT-3 e sett 24 per GT-1b, GT-4).
5. Proporzione di soggetti che durante il trattamento presentano sintomi associati all’interferone come sintomi para-influenzali o sintomi muscoloscheletrici fino alla sett 12.
6. Proporzione di soggetti che raggiunge la SVR24 per gruppo di trattamento.
7. Proporzione di soggetti con SAE, interruzione del trattamento dovuta ad AE e riduzione del dosaggio fino alla fine del follow-up (max 60 sett per GT-2, GT-3 e 72 sett per GT-1b, GT-4)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Infection with the hepatitis C virus (HCV) with underlying mild or moderate hemophilia
• Males 18 years of age and above
• Have not been previously treated with an interferon

• Infezione cronica con HCV GT-1b, GT-2, GT-3 o GT-4 con emofilia lieve o moderata
• Uomini di 18 anni di età o superiore.
• Non sottoposti a precedente trattamento dell’infezione da HCV con interferone o DAAs (antivirali ad azione diretta).

E.4

Principal exclusion criteria

• Not infected with the hepatitis C virus (HCV), hepatitis D virus (HDV) or human immunodeficiency virus (HIV) • Do not have a serious liver, psychiatric, blood, thyroid, lung, heart or eye disease • Presence of Bethesda inhibitor

• Evidenza di coinfezione con HIV o Epatite B. • Evidenza di patologie gravi a carico di fegato, sangue, tiroide, polmone, cuore o malattia dell'occhio. • Evidenza clinica di patologia epatica scompensata. Soggetti con patologia epatica che suggerisce cirrosi/fibrosi grave, supportata da precedente biopsia epatica, Fibroscan od altri criteri clinici inclusi diagnostica per immagini od una storia di patologia epatica scompensata, saranno limitati ad un massimo del 10%. • Storia od attuale evidenza di neoplasia maligna • Storia di patologie gravi o patologie psichiatriche che impedirebbero l’utilizzo di un interferone. • Evidenza clinica di diabete non controllato od ipertensione • Presenza dell’inibitore di Bethesda

E.5 End points

E.5.1

Primary end point(s)

Proportion of subjects who achieve SVR12 (HCV RNA < LLOQ target not detected) at post-treatment follow-up Week 12)

Proporzione di soggetti che raggiunge la SVR12 (HCV RNA < LLOQ target non rilevato alla settimana 12 di follow-up post-trattamento)

E.5.1.1

Timepoint(s) of evaluation of this end point

Analysis of primary endpoint will be conducted after all subjects reach the Post Dosing Treatment Follow-up Week 12.

L'analisi dell'endpoint primario sarà effettuata dopo che tutti i soggetti avranno raggiunto la settimana 12 di follow-up post-trattamento

E.5.2

Secondary end point(s)

1. Proportion of subjects who achieve RVR (HCV RNA < LLOQ target not detected at Week 4) 2. Proportion of subjects who achieve cEVR (HCV RNA < LLOQ target not detected at Week 12) 3. Proportion of subjects who have HCV RNA < LLOQ target not detected at Week 24 4. Proportion of subjects with treatment emergent cytopic abnormalities through end of treatment (Week 12 for GT-2, -3 and Week 24 for GT-1b, -4) 5. Proportion of subjects who experience on-treatment IFN-associated symptoms such as flu-like systems or musculosketletal symptoms through Week 12. 6. Proportion of subjects who achieve SVR24 by treatment group 7. Proportion of subjects with SAEs, discontinuation due to AEs and dose reductions through end of follow-up (maximum of 60 weeks for GT-2, -3 and 72 weeks for GT-1b, -4)

• Proporzione di soggetti che raggiungono la RVR (HCV RNA < LLOQ target non rilevato alla settimana 4) • Proporzione di soggetti che raggiungono la cEVR (HCV RNA < LLOQ target non rilevato alla settimana 12). • Proporzione di soggetti che hanno HCV RNA < LLOQ target non rilevato alla settimana 24 • Proporzione di soggetti con anomalie citopeniche derivate dal trattamento fino alla fine del trattamento (settimana 12 per GT-2. GT-3 e settimana 24 per GT-1b, GT-4). • Proporzione di soggetti che durante il trattamento presentano sintomi associati all’interferone come sintomi para-influenzali o sintomi muscoloscheletrici fino alla settimana 12. • Proporzione di soggetti che raggiunge la SVR24 per gruppo di trattamento. • Proporzione di soggetti con SAE, interruzione del trattamento dovuta ad AE e riduzione del dosaggio fino alla fine del follow-up (per un massimo di 60 settimane per GT-2, GT-3 e 72 settimane per GT-1b, GT-4).

E.5.2.1

Timepoint(s) of evaluation of this end point

Weeks 12 and 24

Settimane 12 e 24

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

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

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

Yes

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Brazil

Russian Federation

United States

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

LPLV

La fine dello studio è definita come LPLV (ultima visita di follow-up post trattamento).

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

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)

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:

117

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

130

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)

At the end of the study, BMS will not continue to supply study drug to
subjects/investigators unless BMS chooses to extend the study. The
investigator should ensure that the subject receives appropriate
standard of care to treat the condition under study

Alla fine dello studio, BMS non continuerà a fornire farmaco in studio ai soggetti/sperimentatori, a meno che BMS decida di estendere lo studio. Lo sperimentatore dovrebbe assicurare che i soggetti ricevano l’appropriato standard of care per trattare la condizione in studio

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

2013-02-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-01-22

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

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IMP with orphan designation in the indication
Orphan Designation Number:
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