Clinical Trials Register

Summary
EudraCT Number:	2012-001942-16
Sponsor's Protocol Code Number:	GS-US-334-0133
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:	2012-08-23
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

Spain - AEMPS

A.2

EudraCT number

2012-001942-16

A.3

Full title of the trial

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo Controlled Study to Investigate the Efficacy and Safety of GS-7977 + Ribavirin for 12 Weeks in Treatment-Naïve and Treatment-Experienced Subjects with Chronic Genotype 2 or 3 HCV Infection.

Ensayo de fase 3, multicéntrico, aleatorizado, doble ciego, controlado con placebo, para investigar la eficacia y seguridad de GS-7977 + ribavirina durante 12 semanas en pacientes con infección por VHC crónica de genotipo 2 ó 3 con o sin tratamiento previo.

A.3.1

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

A study looking at 12 weeks treatment with GS-7977 + Ribavirin for patients with chronic genotype 2 or 3 Hepatitis C infection.

Ensayo de tratamiento a 12 semanas con GS-7977 + Ribavirina para pacientes con infección de hepatitis C crónica de genotipo 2 ó 3.

A.3.2

Name or abbreviated title of the trial where available

VALENCE

A.4.1

Sponsor's protocol code number

GS-US-334-0133

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	Gilead Sciences Inc.
B.1.3.4	Country	United States
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	Gilead Sciences Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Gilead Sciences Inc.
B.5.2	Functional name of contact point	Medical Monitor
B.5.3	Address:
B.5.3.1	Street Address	333 Lakeside Drive
B.5.3.2	Town/ city	Foster City
B.5.3.3	Post code	CA 94404
B.5.3.4	Country	United States
B.5.4	Telephone number	+1650574 3000
B.5.5	Fax number	+1650578 9264
B.5.6	E-mail	clinical.trials@gilead.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.3.2	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.3.10	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: 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	Ribasphere
D.2.1.1.2	Name of the Marketing Authorisation holder	Three Rivers Pharmaceuticals LLC
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
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

Chronic Genotype 2 or 3 HCV Infection

Infección por VHC crónica, con genotipo 2 ó 3.

E.1.1.1

Medical condition in easily understood language

Hepatitis C

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	15.0
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.1.2 Medical condition or disease under investigation

E.1.2	Version	15.0
E.1.2	Level	LLT
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

The primary objectives of this study are:
? To determine the efficacy of treatment with GS-7977+ ribavirin (RBV) compared to treatment with GS-7977 placebo + RBV placebo as measured by the proportion of subjects with sustained viral response 12 weeks after discontinuation of therapy (SVR12)
? To assess the safety and tolerability of GS-7977+RBV compared to placebo control as measured by review of the accumulated safety data

Los objetivos primarios de este ensayo son:
-Determinar la eficacia del tratamiento con GS-7977 + ribavirina (RBV) comparado con el tratamiento con GS-7977 placebo + ribavirina pacebo, medida mediante la proporcíón de pacientes con respuesta viral sostenida 12 semanas después de la interrupción del tratamiento (SVR12).
-Valorar la seguridad y tolerabilidad de GS-7977+RBV comparado con placebo control, medido mediante la revisión de los datos acumulados de seguridad.

E.2.2

Secondary objectives of the trial

The secondary objectives of this study are:
? To determine the proportion of subjects who attain SVR at 4 and 24 weeks after discontinuation of therapy (SVR4 and SVR24)
? To determine the efficacy of treatment with GS-7977+RBV based on prior treatment history
? To evaluate the kinetics of circulating HCV RNA during treatment and after treatment discontinuation
? To evaluate the emergence of viral resistance to GS-7977 during treatment and after treatment discontinuation

Los objetivos secundarios de este ensayo son:
-Determinar la proporción de pacientes que logran SVR a las 4 y 24 semanas tras la interrupción del tratamiento (SVR4 y SVR24).
-Determinar la eficacia del tratamiento con GS-7977+RBV basado en el historial de tratamiento previo.
-Evaluar la cinética del RNA del VHC circulante durante el tratamiento y después de la interrupción del tratamiento.
-Evaluar la aparición de resistencia viral a GS-7977 durante el tratamiento y después de la interrupción del tratamiento.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Pharmacogenomic Substudy:
All subjects will be eligible to participate in the Pharmacogenomic Substudy. A blood sample should be drawn at the Baseline/Day 1 visit if consent is obtained for this Substudy. If not obtained at Baseline/Day 1, the sample may be drawn at any time during the study.

Subestudio farmacogenómico:
Todos los sujetos podrán participar en el Subestudio Farmacogenómico. Deberá tomarse una muestra de sangre en el momento basal/en la visita del Día 1 si se obtiene el consentimiento para este Subestudio. Si no se obtiene en el momento basal/Día 1, la muestra puede obtenerse en cualquier momento durante el ensayo.

E.3

Principal inclusion criteria

1. Willing and able to provide written informed consent
2. Male or female, age ? 18 years
3. Confirmation of chronic HCV infection
4. Classification as treatment naïve or treatment experienced
5. Cirrhosis determination (approximately 20% of subjects may have cirrhosis)
6. Liver imaging within 6 months of Baseline/Day 1 (required in cirrhotic patients only, to exclude hepatocellular carcinoma)
7. Infection with HCV genotype 2 or 3 as determined at Screening
8. HCV RNA ? 10e4 IU/mL at Screening
9. Body mass index (BMI) ? 18 kg/m2
10. Screening ECG without clinically significant abnormalities

1. Estar dispuesto y ser capaz de proporcionar consentimiento informado por escrito.
2. Hombre o mujer, de edad mayor o igual a 18 años.
3. Confirmación de infección por VHC crónica.
4. Clasificación como paciente naive o pretratado.
5. Determinación de cirrosis (aproximadamente el 20% de los pacientes pueden tener cirrosis).
6. Ecografía del hígado en 6 meses desde el nivel basal/Día 1 (sólo requerido en pacientes cirróticos, para excluir carcinoma hepatocelular).
7. Infección por VHC con genotipo 2 ó 3, determinado en el Screening.
8. RNA del VHC mayor o igual a 10e4 UI/ml en el Screening.
9. Indice de masa corporal (BMI) mayor o igual a 18 kg/m2.
10. ECG sin anormalidades clínicamente significativas en el Screening.

E.4

Principal exclusion criteria

1. Prior exposure to a direct-acting antiviral targeting the HCV NS5B polymerase
2. Pregnant or nursing female or male with pregnant female partner
3. Chronic liver disease of a non-HCV etiology
4. Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)
5. Contraindication to RBV therapy
6. History of malignancy diagnosed or treated within 5 years; subjects under evaluation for malignancy are not eligible
7. History of clinically significant hemoglobinopathy
8. Chronic use of systemically administered immunosuppressive agents
9. Clinically-relevant drug or alcohol abuse within 12 months of screening.
10. History of solid organ transplantation
11. Current or prior history of clinical hepatic decompensation

1. Exposición previa a un antiviral de acción directa dirigido a la polimerasa NS5B del VHC.
2. Mujer embarazada o lactante, u hombre cuya mujer esté embarazada.
3. Enfermedad hepática crónica de etiología no-VHC.
4. Infección con virus de hepatitis B (VHB) o virus de inmunodeficiencia humana (VIH).
5. Contraindicación al tratamiento con RBV.
6. Historia de enfermedad maligna diagnosticada o tratada en los últimos 5 años; los sujetos en evaluación por enfermedad maligna, no son elegibles.
7. Historia de hemoglobinopatía clínicamente significativa.
8. Uso crónico de agentes inmunosupresores administrados sistémicamente.
9. Abuso clínicamente relevante de drogas o alcohol en 12 meses desde el screening.
10. Historia de transplante de órgano sólido.
11. Historia clínica previa o actual de descompensación hepática.

E.5 End points

E.5.1

Primary end point(s)

The study hypothesis is that GS-7977+RBV administered for 12 weeks will be superior to placebo. The primary efficacy endpoint is SVR12 (HCV RNA <LLOQ 12 weeks after cessation of therapy).

La hipótesis del ensayo es que GS-7977+RBV administrados durante 12 semanas es superior a placebo. La variable principal de evaluación es SVR12 (RNA del VHC < LLOQ (límite inferior de cuantificación) 12 semanas después de cesar la terapia).

E.5.1.1

Timepoint(s) of evaluation of this end point

12 weeks after cessation of therapy.

12 semanas después de cesar la terapia.

E.5.2

Secondary end point(s)

Secondary efficacy endpoints include the proportion of subjects with HCV RNA < LLOQ at 4 and 24 weeks after discontinuation of therapy (SVR4 and SVR24); viral breakthrough; and relapse.

La variable secundaria de eficacia incluye la proporción de sujetos con RNA del VHC < LLOQ a las 4 y 24 semanas tras la interrupción del tratamiento (SVR4 y SVR24); avance viral; y recaída.

E.5.2.1

Timepoint(s) of evaluation of this end point

4 and 24 weeks after cessation of therapy.

4 y 24 semanas después de cesar la terapia.

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

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

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

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

E.8.6.2

Trial being conducted completely outside of the EEA

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

LVLS

Ultima 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

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.1.1.1

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:

360

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.4.2

For a multinational trial

F.4.2.1

In the EEA

400

F.4.2.2

In the whole clinical trial

400

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)

Subjects in Arm 2 that complete the 12 week treatment period will be offered treatment with GS-7977 + RBV in an open label study (GS-US-334-0109).
Subjects who do not achieve SVR will be eligible for enrollment in a Sequence Registry Study (GS-US-248-0123) to monitor variants in the viral population for up to 3 years.
Subjects who achieve SVR will be eligible for enrollment in the SVR Registry Study (GS-US-248-0122) to evaluate the durability of SVR for up to 3 years post-treatment.

A los sujetos del brazo 2 que completen 12 semanas de tratamiento se les ofrecerá GS-7977+RBV en un ensayo abierto (GS-US-334-0109). Los sujetos que no alcancen SVR podrán entrar en un ensayo de registro de secuencia (GS-US-248-0123) para monitorizar las variantes de la población viral por un periodo de 3 años.
Los sujetos que alcancen SVR podrán entrar en el ensayo de registro de SVR (GS-US-248-0122) para evaluar la duración de la SVR por un periodo de 3 años después del tratamiento.

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

2012-09-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-09-14

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-01-08

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