Clinical Trials Register

Summary
EudraCT Number:	2012-000571-16
Sponsor's Protocol Code Number:	GS-US-334-0109
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:	2012-09-26
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

2012-000571-16

A.3

Full title of the trial

An Open-Label Study of GS-7977+ Ribavirin for 12 Weeks in Subjects with Chronic HCV Infection who Participated in Prior Studies Evaluating GS-7977.

Estudio abierto de GS-7977 + ribavirina durante 12 semanas en
sujetos con infección crónica por el VHC que participaron en
estudios previos que evaluaron GS-7977

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 who previously took part in Gilead-sponsored GS-7977 studies in the control arms.

Estudio de 12 semanas de tratamiento con GS-7977+Ribavirina en pacientes con Hepatitis C crónica genotipo 2 que participaron ne estudios de Gilead con GS-7977 en los brazos de control.

A.4.1

Sponsor's protocol code number

GS-US-334-0109

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.3.1	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.3.10	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

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 crónica por el VHC genotipo 2 ó 3.

E.1.1.1

Medical condition in easily understood language

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 GS-7977 + RBV as measured by the proportion of subjects with sustained viral response at 12 weeks after discontinuation of therapy (SVR12).
? To evaluate the safety and tolerability of GS-7977 + RBV as assessed by review of the accumulated safety data.

Los objetivos principales de este estudio son:
? Determinar la eficacia de GS-7977 + RBV medida mediante la
proporción de sujetos con respuesta viral sostenida 12 semanas
después de la interrupción del tratamiento (RVS12).
? Evaluar la seguridad y la tolerabilidad de GS-7977 + RBV
valoradas mediante la revisión de los datos de seguridad
acumulados.

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 evaluate the kinetics of circulating HCV RNA during and after treatment discontinuation
? To evaluate the emergence of viral resistance to GS-7977 during and after treatment discontinuation

Los objetivos secundarios de este estudio son:
? Determinar la proporción de sujetos que alcanzan la RVS 4 y
24 semanas después de la interrupción del tratamiento (RVS4 y
RVS24)
? Evaluar la cinética del ARN circulante del VHC durante y
después de la interrupción del tratamiento
? Evaluar la aparición de resistencia viral a GS-7977 durante y
después de la interrupción del tratamiento

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Willing and able to provide written informed consent
2. HCV Genotype 2 or 3
3. Subject must have participated in a prior study of GS-7977 (PSI-7977)
4. HCV RNA >LLOQ
5. Screening ECG without clinically significant abnormalities
6. Subjects must have a number of laboratory parameters within defined ranges at screening
7. A female subject is eligible to enter the study if it is confirmed that she is:
a) Not pregnant or nursing
b) Of non-childbearing potential
c) Of childbearing potential but with a negative serum pregnancy test at screening and a negative urine pregnancy test on the Baseline/Day 1 visit prior to randomization and agree to one of the described forms of contraception during the course of the study and up to 7 months following cessation of Ribavirin therapy.
8. All male study participants must agree to consistently and correctly use a condom while their female partner agrees to use 1 of the methods of birth control listed in the protocol from the date of screening until 7 months after their last dose of RBV.
9. Male subjects must agree to refrain from sperm donation for at least 7 months after the last dose of RBV.
10. Subject must be of generally good health as determined by the Investigator.
11. Subject must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments.

1. Estar dispuestos y ser capaces de proporcionar su consentimiento informado por escrito
2. VHC con genotipo 2 o 3
3. El sujeto debe haber participando en un estudio previo de GS-7977 (PSI-7977)
? La elegibilidad para participar en este estudio se definirá en el estudio previo (progenitor) de GS-7977 (PSI-7977) con respecto a la asignación previa al tratamiento, el resultado del tratamiento y la realización de las evaluaciones programadas. Como mínimo, un sujeto debe haber realizado todas las evaluaciones de selección y cumplir todos los criterios de elegibilidad del estudio progenitor. Los pacientes posiblemente elegibles son, entre otros, aquellos que recibieron placebo o PEG/RBV en un brazo control.
? Si en el estudio progenitor no se define la elegibilidad, esta puede determinarla el Monitor Médico individualmente en cada caso. El Monitor Médico tendrá en cuenta la asignación previa al tratamiento, el resultado del tratamiento y la realización de las
evaluaciones programadas en el estudio progenitor.
4. ARN del VHC >LIC
5. ECG de la selección sin alteraciones clínicamente significativas
6. Los sujetos deben tener determinados parametros analíticos en la selección.
7. Una paciente es elegible para ser incluida en el estudio si se confirma que:
a) No está embarazada ni dando lactancia materna
b) No tiene capacidad fértil (es decir, mujeres que han sido sometidas a una histerectomía, a quienes se les han extirpado los dos ovarios o presentan insuficiencia ovárica médicamente documentada o son posmenopáusicas ? mujeres > 50 años de
edad con cese (durante ?12 meses) de la menstruación que tenían anteriormente)
c) Tiene capacidad fértil (es decir, mujeres que no han sido sometidas a una histerectomía, a quienes no se les han extirpado los dos ovarios ni presentan insuficiencia ovárica médicamente documentada). Se considerará que las mujeres ? 50 años de edad con amenorrea tienen capacidad fértil. Dichas mujeres deben tener una prueba de embarazo en suero negativa en la selección y una prueba de embarazo en orina negativa en la visita Basal/del Día 1 antes de la aleatorización y deben acceder a tomar una de las medidas descritas desde 3 semanas antes de la visita
Basal/del Día 1 hasta 6 meses después de la última dosis de RBV.
8. Todos los participantes varones deben acceder a utilizar de forma constante y correcta un preservativo mientras su pareja de sexo femenino accede a utilizar 1 de los métodos anticonceptivos enumerados anteriormente desde la fecha de la selección hasta 7 meses después de la última dosis de RBV.
9. Los sujetos varones deben acceder a abstenerse de donar esperma durante al menos 7 meses después de la última dosis de RBV.
10. El sujeto debe tener un buen estado de salud general según lo determine el Investigador.
11. El sujeto debe ser capaz de cumplir con las instrucciones de dosificación para la administración del fármaco del estudio y ser capaz de realizar el calendario de evaluaciones del estudio.

E.4

Principal exclusion criteria

1. Pregnant or nursing female or male with pregnant female partner
2. Current or prior history of clinical hepatic decompensation (e.g., ascites, jaundice, encephalopathy or variceal hemorrhage).
3. Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)
4. Chronic use of systemically administered immunosuppressive agents (e.g., prednisone equivalent > 10 mg/day)
5. Active substance abuse which, in the opinion of the investigator, would make the candidate inappropriate for participation in this study.
6. Use of any prohibited concomitant medications as described in Section 5.6 within 28 days of the Baseline/Day 1 visit

1. Mujer embarazada o dando lactancia materna o varón cuya pareja está embarazada
2. Presencia o antecedentes previos de descompensación hepática clínica (p. ej., ascitis, ictericia, encefalopatía o hemorragia varicosa).
3. Infección por el virus de la hepatitis B (VHB) o por el virus de la inmunodeficiencia
humana (VIH)
4. Utilización crónica de inmunosupresores administrados por vía sistémica (p. ej., > 10 mg/día de equivalentes de prednisona)
5. Abuso activo de sustancias que, según la opinión del investigador, haría que el candidato fuera inapropiado para participar en este estudio.
6. Utilización de medicaciones concomitantes prohibidas según se describe en la Sección 5.6 en los 28 días anteriores a la visita Basal/del Día 1.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is SVR12 (HCV RNA <LLOQ 12 weeks after discontinuation of therapy) in the FAS population.
The primary safety endpoint is any AE leading to permanent discontinuation of study drug(s).

La variable principal de eficacia es la RVS12 (ARN del VHC < LIC 12 semanas después de la interrupción del tratamiento) en la población del GAC.
La variable principal de seguridad es cualquier AA que da lugar a interrupción permanente del/de los fármaco(s) del estudio.

E.5.1.1

Timepoint(s) of evaluation of this end point

Efficacy endpoint: 12 weeks after cessation of therapy.
Safety endpoint: throughout the duration of therapy.

Variable de eficacia: 12 semanas después de la interrupción del tratamiento.
Variable de seguridad: a lo largo de la duración del tratamiento.

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.

Las variables secundarias de eficacia son la proporción de sujetos con: ARN del VHC < LIC 4 y 24 semanas después de la interrupción del tratamiento (RVS4 y RVS24), la exacerbación viral y la recidiva.

E.5.2.1

Timepoint(s) of evaluation of this end point

4 and 24 weeks after the cessation of therapy.

4 semanas y 24 semanas después de la interrupción del tratamiento.

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

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

Information not present in EudraCT

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.8.3

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

New Zealand

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

LVLS

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:

180

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

F.4.2.2

In the whole clinical trial

200

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 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.

Los sujetos que no alcancen la RVS serán elegibles para su inclusión en el Estudio de Registro de Secuencias (GS-US-248-0123) para monitorizar variantes en la población viral hasta 3 años.
Todos los sujetos que alcancen la RVS serán elegibles para su inclusión en el Estudio de
Registro de RVS (GS-US-248-0122) para evaluar la duración de la RVS durante hasta 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

2012-11-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-11-15

P. End of Trial
P.	End of Trial Status	Completed

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