Clinical Trials Register

Summary
EudraCT Number:	2012-002417-19
Sponsor's Protocol Code Number:	GS-US-334-0126
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:	2012-09-14
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

2012-002417-19

A.3

Full title of the trial

A Phase 2, Multicenter, Open-Label Study to Investigate the Safety and Efficacy of GS-7977 and Ribavirin for 24 weeks in Subjects with Recurrent Chronic HCV Post Liver Transplant

Estudio de fase 2, multicéntrico, abierto, para investigar la seguridad y la eficacia de GS-7977 y ribavirina durante 24 semanas en sujetos con VHC recurrente crónico tras trasplante de hígado

A.3.1

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

A study of GS-7977 and Ribavirin in patients who have hepatitis C and have received a liver transplant

Estudio de GS-7977 Ribavirina en pacientes con hepatitis C y que han recibido transplante de hígado

A.4.1

Sponsor's protocol code number

GS-US-334-0126

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

Recurrent Chronic HCV Post Liver Transplant

Hepatitis C crónica recurrente tras transplante de hígado

E.1.1.1

Medical condition in easily understood language

Hepatitis C in patients who have received a liver transplant

Hepatitis C en pacientes que han recibido transplante de hígado

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

To determine the antiviral efficacy of combination therapy with GS-7977 + ribavirin for 24 weeks in subjects with recurrent HCV post liver transplant as measured by sustained virologic response 12 weeks after discontinuation of therapy (SVR12 defined as HCV RNA < lower limit of quantitation [LLoQ] 12 weeks after last dose of study drug).

Determinar la eficacia antiviral de la terapia combinada de GS-7977 + ribavirina (RBV) durante 24 semanas en sujetos con infección recurrente por VHC tras trasplante de hígado, medida mediante la respuesta virológica sostenida 12 semanas después de interrumpir la terapia (RVS12, definida como ARN del VHC < límite inferior de cuantificación [LLoQ] 12 semanas después de la última dosis del fármaco del estudio).

E.2.2

Secondary objectives of the trial

To evaluate the safety and tolerability of this regimen in this patient population
To determine the proportion of subjects who attain sustained virologic response at 4, 24 and 48 weeks after discontinuation of therapy (SVR4, SVR24 and SVR48)
To evaluate the emergence of viral resistance to GS-7977 during and after treatment discontinuation.
To evaluate the kinetics of circulating HCV RNA during and after treatment

Evaluar la seguridad y tolerabilidad de estos regímenes en esta población de pacientes.
Determinar la proporción de sujetos que alcanzan la respuesta virológica sostenida (RVS) a las 4, 24 y 48 semanas posteriores a la interrupción del tratamiento (RVS4, RVS24 y RVS48).
Evaluar la aparición de resistencia vírica a GS-7977 durante el tratamiento y tras la interrupción del mismo.
Evaluar la cinética del ARN circulante del VHC durante el tratamiento y tras la interrupción del mismo.

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

Pharmacogenomics substudy
To identify or validate genetic markers that may be predictive of the natural history of disease, virologic response to therapy and/or the tolerability of medical therapies through genetic discovery research, in subjects who provide a separate and specific consent

Subestudio de farmacogenómica
Para identificar o validar marcadores genéticos que pueden ser predictivos de la historia natural de la enfermedad, la respuesta virológica a la terapia y/o la tolerabilidad a las terapias médicas a través de la investigación genética, en sujetos que proporcionen un consentimiento separado y específico

E.3

Principal inclusion criteria

1. Willing and able to provide written informed consent
2. Males or females, age > or = 18 years old
3. Subjects with evidence of chronic HCV (all genotypes) documented pretransplantation
4. HCV RNA > or = 10000 IU/mL at screening
5. Absence of organ rejection as documented by post transplant liver biopsy taken no more than 12 months prior to Baseline/Day 1 visit
6. Primary or secondary (retransplant), liver alone or liver and kidney transplant recipient from deceased or living donor (regardless of the HCV status of the liver donor)
7. Liver transplant > or = 6 months and < or = 150 months prior to screening
8. Naïve to all nucleotides/nucleoside treatments for chronic HCV infection
9. A body mass index (BMI) of > or = 18 kg/m2

1. Ser capaces y estar dispuestos a proporcionar el consentimiento informado por escrito.
2. Varones y mujeres, de edad > o = a 18 años.
3. Sujetos con evidencia de VHC crónico (todos los genotipos) documentado antes del trasplante.
4. ARN del VHC > o = 10000 UI/ml en la selección.
5. Ausencia de rechazo del órgano documentada mediante biopsia hepática postrasplante, realizada no más de 12 meses antes de la visita de inicio/día 1.
6. Receptor de trasplante primario o secundario (retrasplante), de hígado solo o hígado y riñón, procedente de un fallecido o de donante vivo. (independientemente del estatus del VHC del donante de hígado).
7. Trasplante de hígado > o = 6 meses y < or = 150 meses antes de la selección.
8. Sin tratamiento previo con nucleótidos/nucleósidos contra la infección crónica por VHC.
9. Índice de masa corporal (IMC) de > o = 18 kg/m2.

E.4

Principal exclusion criteria

1. Multi-organ transplant that includes heart or lung recipient
2. Subjects with de novo or recurrent Hepatocellular Carcinoma (HCC) post transplant based on center specific screening protocol
3. Current use of corticosteroids at any dose > 5mg of prednisone/day (or equivalent dose of corticosteroid)
4. Child-Pugh-Turcotte Score CPT > 7 at screening
5. MELD score > 17 at screening
6. Recipient of ABO incompatible organ
7. Histological evidence of unresolved rejection
8. Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV) at screening
9. Current, uncontrolled ascites, variceal hemorrhage, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, or other signs of decompensated cirrhosis
10. Serum creatinine >2.5x upper limit of normal or stage 4 chronic kidney disease (CrCl <30ml/min)
18. Treatment with IFN, RBV, telaprevir or boceprevir or any other approved or experimental medication with known anti-HCV activity within 3 months prior to Baseline/Day 1 visit
19. Screening ECG with clinically significant abnormalities
20. Participation in a clinical study with an investigational drug, or biologic within 3 months prior to first dose administration at the Baseline/Day 1 Visit

1. Trasplante multiorgánico que incluya receptores de corazón o pulmón.
2. Sujetos con carcinoma hepatocelular (CHC) de novo o recurrente postrasplante, según el protocolo de selección específico del centro.
3. Uso habitual de corticosteroides a cualquier dosis >5 mg de prednisona/día (o dosis equivalente de otro corticoide).
4. Escala Child-Pugh-Turcotte (CPT) > 7 en la selección.
5. Escala MELD > 17 en la selección.
6. Receptor de órgano ABO incompatible.
7. Evidencia histológica de rechazo no resuelto.
8. Infección con virus de la hepatitis B (VHB) o virus de la inmunodeficiencia humana (VIH) en la selección.
9. Presencia de ascitis no controlada, varices hemorrágicas, encefalopatía hepática, síndrome hepatorrenal, síndrome hepatopulmonar o cualquier signo de cirrosis descompensada.
10. Creatinina en suero > 2,5x límite superior normal o afección renal crónica en estadio 4 (Aclaramiento de creatinina, ACr < 30 ml/min).
18. Tratamiento con IFN, RBV, telaprevir o boceprevir o cualquier otro medicamento, aprobado o experimental, con actividad anti-VHC conocida en los 3 meses previos al día 1 del estudio.
19. ECG realizado en la selección con anomalías clínicamente significativas.
20. Participación en un estudio clínico con un fármaco experimental, o biológico, dentro de los 3 meses anteriores a la administración de la primera dosis en la visita de inicio/día 1.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is SVR12 (HCV RNA < lower limit of quantitation [LLoQ] 12 weeks after last dose of study drug) for subjects in the Full Analysis Set.

El criterio de valoración de la eficacia primario para este estudio será la proporción de sujetos con RVS12, definida como ARN VHC < LLoQ 12 semanas después de dejar el fármaco del estudio.

E.5.1.1

Timepoint(s) of evaluation of this end point

12 weeks after last dose of study drug

12 semanas tras la última dosis del fármaco del estudio

E.5.2

Secondary end point(s)

The secondary efficacy endpoints include the proportion of subjects who attain sustained virologic response at 4, 24 and 48 weeks after discontinuation of therapy (SVR4, SVR24 and SVR48); proportion of subjects who have HCV RNA < LLoQ by visit while on treatment; absolute and change from baseline in HCV RNA through Week 8; and virologic failure.

Los criterios de valoración secundarios incluyen la proporción de sujetos que logran respuesta virológica sostenida en las semanas 4,24, y 48 después de la discontinuación de la terapia (SVR4, SVR24, y SVR48); proporción de sujetos con ARN VHC < LLoQ por visita, los valores absolutos y cambios con respecto al inicio en el ARN del VHC hasta la semana 8 por visita, y la proporción de sujetos con fallo vírico.

E.5.2.1

Timepoint(s) of evaluation of this end point

4, 24 and 48 weeks after last dose of study drug

4, 24 y 48 semanas después de la última dosis del fármaco en estudio

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)

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

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

Yes

E.8.4

The trial involves multiple sites in the 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

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 (48 weeks after last dose of study drug)

Última visita del último paciente (48 semanas después de la última dosis del fármaco en estudio)

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:

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

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.

Sujetos que no alcancen SVR serán elegidos para entrar en el Estudio de Registro de Secuencia (GS-US-248-0123) para monitorizar variantes en la población viral durante 3 años.
Los sujetos que alcancen SVR serán elegidos para entrar en el SVR Estudio de Registro (GS-US-248-0122) para evaluar la durabilidad de SVR durante 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