Clinical Trials Register

Summary
EudraCT Number:	2014-003446-27
Sponsor's Protocol Code Number:	TMC435HPC3021
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-10-20
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

Spain - AEMPS

A.2

EudraCT number

2014-003446-27

A.3

Full title of the trial

A Phase 3, Multicenter, Open-Label, Single-Arm Study to Investigate the Efficacy and Safety of a 12-Week Regimen of Simeprevir in Combination with Sofosbuvir in Treatment-Naïve or -Experienced Subjects with Chronic Genotype 4 Hepatitis C Virus Infection

Estudio Fase 3, multicéntrico, abierto, con una sola rama de tratamiento para investigar la eficacia y seguridad de un régimen de tratamiento de 12 semanas de Simeprevir en combinación con Sofosbuvir en pacientes con infección crónica por el virus de la hepatitis C de genotipo 4, que no han recibido tratamiento previo o previamente tratados.

A.3.1

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

Efficacy and Safety Study of Simeprevir in Combination with Sofosbuvir in Subjects with Chronic Genotype 4 Hepatitis C Virus Infection

Estudio de la eficacia y seguridad de Simeprevir en combinación con Sofosbuvir en pacientes con infección crónica por virus de la hepatitis C genotipo 4.

A.4.1

Sponsor's protocol code number

TMC435HPC3021

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	Janssen R&D Ireland
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	Janssen R&D Ireland
B.4.2	Country	Ireland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Janssen-Cilag, S.A.
B.5.2	Functional name of contact point	Global Clinical Operations
B.5.3	Address:
B.5.3.1	Street Address	Pº de las Doce Estrellas, 5-7
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28042
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34917228100
B.5.5	Fax number	+34917228628
B.5.6	E-mail	agonza45@its.jnj.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	Yes
D.2.1.1.1	Trade name	Simeprevir (Olysio)
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag International NV
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	JNJ-38733214-AAA-Capsule (G28), Hard 150mgs
D.3.2	Product code	TMC435
D.3.4	Pharmaceutical form	Capsule, hard
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	Simeprevir
D.3.9.2	Current sponsor code	TMC435
D.3.9.3	Other descriptive name	JNJ-38733214-AAA
D.3.9.4	EV Substance Code	SUB26723
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	150
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	Sovaldi
D.2.1.1.2	Name of the Marketing Authorisation holder	Gilead Sciences International Ltd.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Sofosbuvir
D.3.2	Product code	GS-7977
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	Sofosbuvir
D.3.9.1	CAS number	1190307-88-0
D.3.9.2	Current sponsor code	GS-7977
D.3.9.4	EV Substance Code	SUB32080
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	400
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	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	Simeprevir (Olysio)
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag International NV
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	JNJ-38733214-AAA-Capsule (G19), Hard 150mgs
D.3.2	Product code	TMC435
D.3.4	Pharmaceutical form	Capsule, hard
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	Simeprevir
D.3.9.2	Current sponsor code	TMC435
D.3.9.3	Other descriptive name	JNJ-38733214-AAA
D.3.9.4	EV Substance Code	SUB26723
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	150
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

Hepatitis C-Infection genotype 4 Patients

Pacientes con infección por hepatitis C- genotipo 4

E.1.1.1

Medical condition in easily understood language

Hepatitis C is an infectious disease affecting the liver, caused by hepatitis C virus

La hepatitis C es una enfermedad infecciosa que afecta el hígado, causada por el virus de la hepatitis C

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	17.0
E.1.2	Level	PT
E.1.2	Classification code	10019744
E.1.2	Term	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 show superiority of SMV (150 mg qd) in combination with SOF (400 mg qd) for 12 weeks versus a historical control, with respect to the proportion of subjects with sustained virologic response 12 weeks after end of treatment (EOT) (SVR12) in the overall population

Demostrar la superioridad del tratamiento de 12 semanas con SMV (150 mg una vez al día [1 v/d]) en combinación con SOF (400 mg 1 v/d) frente a un control histórico, respecto a la proporción de pacientes de la población global que presenten respuesta virológica sostenida 12 semanas después del final del tratamiento (FDT) (RVS12).

E.2.2

Secondary objectives of the trial

?To investigate the efficacy of a 12-week regimen of SMV in combination with SOF with respect to the proportion of subjects with SVR 4 and 24 weeks after EOT (SVR4 and SVR24, respectively) in the overall population.
?To investigate the on-treatment virologic responses of SMV in combination with SOF at all time points.
?To investigate the safety and tolerability of a 12-week regimen of SMV in combination with SOF.
?To evaluate the frequency of on-treatment failures, including viral breakthrough.
?To evaluate the frequency of viral relapse.
?To assess changes from baseline in the HCV NS3/4A and NS5B sequences in subjects not achieving SVR.

Investigar la eficacia de un régimen de tratamiento de 12 semanas de SMV en combinación con SOF respecto a la proporción de pacientes de la población global que presenten RVS 4 y 24 semanas después del FDT (RVS4 y RVS24, respectivamente). Investigar las respuestas virológicas durante el tratamiento con SMV en combinación con SOF en todos los momentos de evaluación. Investigar la seguridad y tolerabilidad de un régimen de tratamiento de 12 semanas de SMV en combinación con SOF. Evaluar la frecuencia de fracasos durante el tratamiento, incluidos los rebotes virales. Evaluar la frecuencia de recidivas virales. Evaluar las variaciones respecto al momento basal en las secuencias de NS3/4A y NS5B del VHC en los pacientes que no alcanzan la RVS.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

.Subjects with confirmed hepatitis C virus (HCV) with HCV RNA greater than (>) 10000 international unit per milliliter (IU/mL)
.Subjects who are treatment naive or treatment-experienced.
.Subjects must have documentation of a liver biopsy or fibroscan or agree to have one during screening
.Subjects with cirrhosis must have an hepatic imaging procedure (ultrasound, CT scan or magnetic resonance imaging [MRI]) within 6 months before the screening visit (or during the screening period) with no findings suspicious for hepatocellular carcinoma (HCC)
.Women of childbearing potential or men with a female partner of childbearing potential must agree to use an effective form of contraception, or not be heterosexually active, or of nonchildbearing potential

Pacientes con infección crónica por el VHC , una concentración de ARN del VHC en plasma de >10.000 UI/ml. Se incluirá tanto a pacientes que no hayan recibido tratamiento previo como a pacientes previamente tratados. Los pacientes deberán tener documentación de una biopsia hepática o fibroscan o acceder a que se les realicen durante el período de selección. Los pacientes que presenten cirrosis deberán someterse a una procedimiento de diagnóstico hepático por imágen (ecografia, tomografía computerizada o resonancia magnética (RM)) en los 6 meses previos a la visita de selección ( o durante el proceso de selección), sin hallazgos sospechosos de carcinoma hepatocelular (CHC). Las mujeres en edad fértil y los hombres conpareja femenina en edad fértil deberán comprometerse a unsar un método anticonceptivo adecuado, o a no ser heterosexualmente activos o a no estar en edad fértil.

E.4

Principal exclusion criteria

.Evidence of clinical hepatic decompensation
.Any liver disease of non-HCV etiology
.Subjects with a past history of treatment with an approved or investigational DAA - Co-infection with human immunodeficiency virus (HIV) type 1 or type 2 (HIV-1 or HIV-2) (positive HIV-1 or HIV-2 antibodies test at screening)
.Infection/co-infection with HCV non-genotype 4

Evidencia de descompensación hepática clínica. Cualquier hepatopatía con una etiología distinta del VHC.
Pacientes con antecedentes de tratamiento con un ADD aprobado o en investigación. Coinfección con el virus de la inmunodeficiencia humana (VIH) tipo 1 o tipo 2 (VIH-1 o VIH-2) o anticuerpos positivos para el VIH-1 o VIH-2 en el momento de la selección. Infección o co-infección VHC distinto del de genotipo 4

E.5 End points

E.5.1

Primary end point(s)

.Percentage of Subjects With Sustained Virologic Response (SVR 12) at Week 12 After End of Treatment (EOT)

Porcentaje de pacientes con respuesta virológica sostenida (RVS 12) en la semana 12 después del final del tratamiento (FDT)

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 12 after EOT

Semana 12 despues de fin de tratamiento

E.5.2

Secondary end point(s)

.Percentage of Subjects With Sustained Virologic Response at Week 4 (SVR 4) and 24 (SVR 24) After EOT
.Percentage of Subjects With On-treatment Virologic Response of Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
.Percentage of Subjects With on-treatment failure along with Viral Breakthrough
.Percentage of Subjects With Viral Relapse

Porcentaje de pacientes con respuesta virológica sostenida en la semana 4 (RVS 4) y 24 (RVS 24) Después de fin de tratamiento
porcentaje de pacientes con respuesta virológica al ácido ribonucleico (ARN) del virus de la hepatitis C (VHC) durante el tratamiento. Porcentaje de pacientes con fracaso en el tratamiento junto con rebote viral. Porcentaje de pacientes con recaída viral

E.5.2.1

Timepoint(s) of evaluation of this end point

.Week 4 and 24 after EOT
.Baseline, Week 1, 2, 3, 4 and 8
.Baseline up to EOT (Week 12)
.Week 4, 12 and 24 after EOT

Semana y y 24 después del fin de tratamiento (FDT). Visita basal, semana 1, 2, 3, 4 y 8.
Visita basal hasta el fin de tratamiento (FDT). Semana 4, 12 y 24 después del fin de tratamiento (FDT).

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

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

Yes

E.6.13.1

Other scope of the trial description

Tolerability

Tolerabilidad

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

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)

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

LSLV

Última visita del último paciente

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:

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

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

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)

None

Ninguno

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

2015-01-02

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-12-12

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-12-23

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