Clinical Trials Register

Summary
EudraCT Number:	2012-004154-28
Sponsor's Protocol Code Number:	GS-US-334-0124
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:	2013-03-06
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

2012-004154-28

A.3

Full title of the trial

A Phase 3, Open-label Study to Investigate the Efficacy and Safety of Sofosbuvir plus Ribavirin in Chronic Genotype 1, 2, 3 and 4 Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) Co-infected Subjects

Estudio abierto de fase III para investigar la eficacia y la seguridad de sofosbuvir más ribavirina en sujetos coinfectados con los genotipos 1, 2, 3 y 4 del virus de la hepatitis C (VHC) crónica y con el virus de la inmunodeficiencia humana (VIH)

A.3.1

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

A study with sofosbuvir and ribavirin in patients co-infected with HIV and HCV

Estudio con sofosbuvir y ribavirina en pacientes coinfectados con VIH y VHC

A.3.2

Name or abbreviated title of the trial where available

PHOTON 2

A.4.1

Sponsor's protocol code number

GS-US-334-0124

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.3.9.3	Other descriptive name	GS-7977
D.3.9.4	EV Substance Code	SUB75008
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

Hepatitis C Virus Infection

Infección con el Virus de la Hepatitis C

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	15.1
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	15.1
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

The primary objectives of this study are:
? To determine the efficacy of treatment with SOF + RBV as measured by the proportion of subjects with sustained viral response 12 weeks after discontinuation of therapy (SVR12)
? To evaluate the safety and tolerability of SOF + RBV as assessed by review of the accumulated safety data, including HIV-RNA and CD4 T-cell percent

Los objetivos principales de este estudio son los siguientes:
?Determinar la eficacia del tratamiento con sofosbuvir (SOF) + ribavirina (RBV) a través de la proporción de sujetos que presentan una respuesta vírica sostenida 12 semanas después de suspender el tratamiento (RVS12).
?Evaluar la seguridad y la tolerabilidad de SOF + RBV mediante la revisión de los datos de seguridad acumulados.

E.2.2

Secondary objectives of the trial

The secondary objectives of this study are as follows:
? 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 treatment and after treatment discontinuation
? To evaluate the emergence of viral resistance to SOF during treatment and after treatment discontinuation

Los objetivos secundarios de este estudio son los siguientes:
?Determinar la proporción de sujetos que alcanzan la RVS a las 4 y a las 24 semanas de suspender el tratamiento (RVS4 y RVS24).
?Evaluar la cinética del ARN del VHC circulante durante el tratamiento y después de suspenderlo.
?Evaluar la aparición de resistencia vírica al SOF durante el tratamiento y después de suspenderlo.

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
The objective of this substudy is to identify or validate genetic markers that may predict the natural history of disease, response to therapy and/or the tolerability of medical therapies through genetic discovery research, in subjects who provide their separate and specific consent and provided this substudy is approved locally.

Subestudio Farmacogenómico
El objetivo de este subestudio es detectar o validar marcadores genéticos que puedan pronosticar la evolución natural de la enfermedad, la respuesta al tratamiento y/o la tolerabilidad de los tratamientos médicos mediante la investigación genética en sujetos que otorguen su consentimiento independiente y específico, y siempre que este subestudio cuente con la aprobación local.

E.3

Principal inclusion criteria

1. Willing and able to provide written informed consent
2. Male or female, age ? 18 years with chronic HCV and HIV-1 infection
3. HCV RNA > 1 x 104 IU/mL at Screening
4. Infection with HCV genotype 1, 2, 3, or 4 as determined at Screening
5. HIV-1 infection confirmed with positive ELISA and Western blot at Screening (if necessary)
6. The subject?s medical records must be sufficient to be categorized on IFN eligibility or prior treatment with PEG/RBV into one of the following categories as defined in Section 6.4.2:
a) Treatment Naïve - IFN-eligible (genotypes 1, 2, 3 and 4)
b) Treatment Naïve - IFN-ineligible (genotypes 1, 2, 3 and 4)
c) Treatment Experienced - IFN Intolerant (genotypes 2 and 3)
d) Treatment Experienced - Non-Response (genotypes 2 and 3)
e) Treatment Experienced - Relapse/Breakthrough (genotypes 2and 3)
7. Confirmation of chronic HCV infection
8. Ability to determine the presence/absence of cirrhosis

1.Estar dispuestos y ser capaces de otorgar su consentimiento informado por escrito.
2.Varón o mujer de edad ? 18 años con infección crónica del VHC y el VIH-1.
3.ARN del VHC > 1 x 104 UI/ml en la selección.
4.Infección con los genotipos 1, 2, 3 o 4 del VHC en el momento de la selección.
5.Infección con el VIH-1 confirmada mediante ELISA y Western blot positivos en el momento de la selección (si es necesario).
6.Los historiales médicos del sujeto deben ser suficientes como para poder asignarlos según su idoneidad para el IFN o el tratamiento previo con PEG/RBV a una de las categorías siguientes establecidas en el apartado 6.4.2:
a)No tratado anteriormente - apto para IFN (genotipos 1, 2, 3 y 4)
b)No tratado anteriormente - no apto para IFN (genotipos 1, 2, 3 y 4)
c)Tratado anteriormente - intolerante al IFN (genotipos 2 y 3)
d)Tratado anteriormente - sin respuesta (genotipos 2 y 3)
e)Tratado anteriormente - recidiva/rebrote (genotipos 2 y 3)
7.Confirmación de una infección crónica por el VHC
8.Capacidad para determinar la presencia o ausencia de cirrosis.

E.4

Principal exclusion criteria

1. Non-genotype 1/2/3/4 or mixed genotype at Screening
2. Genotype 1 or 4 with prior treatment for HCV
3. Poor control with ARV regimen requiring a possible dose modification of therapy within 4 weeks of SOF dosing
4. Prior exposure to a direct-acting antiviral targeting the HCV NS5B polymerase.
5. Pregnant or nursing female or male with pregnant female partner
6. Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson?s disease, ?1 antitrypsin deficiency, cholangitis)
7. A new AIDS-defining condition diagnosed within 30 days prior to screening
8. Active, serious infection (other than HIV or HCV) requiring parenteral antibiotics, antivirals or antifungals within 30 days prior to Baseline
9. Infection with hepatitis B virus (HBV)
10. Contraindication to RBV therapy
11. History of malignancy diagnosed or treated within 5 years

1.Genotipos distintos de 1/2/3/4 o genotipo mixto en la selección.
2.Genotipos 1 o 4 con tratamiento previo contra el VHC.
3.Control inadecuado con el tratamiento ARV que requiera una posible modificación de la dosis en las 4 semanas previas a recibir SOF.
4.Exposición previa a un antivírico de acción directa dirigido a la polimerasa NS5B del VHC.
5.Mujer embarazada o en período de lactancia o varón con pareja embarazada.
6.Hepatopatía crónica de etiología ajena al VHC (p. ej., hemocromatosis, enfermedad de Wilson, deficiencia de ?1-antitripsina, colangitis).
7.Diagnóstico de una nueva enfermedad característica del sida en los 30 días previos a la selección.
8.Infección activa grave (distinta del VIH-1 o del VHC) que requiera un tratamiento antibiótico, antivírico o antifúngico por vía parenteral en los 30 días previos a la visita inicial.
9.Infección del virus de la hepatitis B (VHB).
10.Tratamiento con RBV contraindicado.
11.Antecedentes de neoplasia maligna diagnosticada o tratada en los 5 años anteriores

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is SVR12 (HCV RNA <LLOQ 12 weeks after cessation of therapy).

El criterio de valoración principal de la eficacia es RVS12 (ARN del VHC < LMC 12 semanas después de suspender el tratamiento).

E.5.1.1

Timepoint(s) of evaluation of this end point

12 Weeks post last dose of study drug.

12 Semanas despues de la última dosis del fármaco del estudio

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); HCV RNA < LLOQ on-treatment virologic failure, and change in HCV RNA from baseline through Week 8.

Los criterios de valoración secundarios de la eficacia incluyen la proporción de sujetos que presenten: ARN del VHC < LMC a las 4 y 24 semanas después de suspender el tratamiento (RVS4 y RVS24), ARN del VHC < LMC para el fracaso vírico durante el tratamiento, y un cambio en el ARN del VHC con respecto al valor inicial hasta la semana 8.

E.5.2.1

Timepoint(s) of evaluation of this end point

4 and 24 Weeks post last dose of study drug.

4 y 24 Semanas después de la última dosis del fármaco del 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)

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

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

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

France

Germany

Italy

Portugal

Spain

United Kingdom

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, 24 weeks after cessation of therapy

LVLS, 24 semanas despues de la finalización del tratamiento

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:

198

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

205

F.4.2.2

In the whole clinical trial

220

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 aptos para inscribirse en el estudio de registro de secuencias (GS-US-248-0123) para controlar la persistencia de mutaciones resistentes durante un máximo de 3 años.
Los sujetos que alcancen la RVS serán aptos para inscribirse en el estudio de registro de la RVS GS-US-2480122) para evaluar la durabilidad de la RVS hasta un máximo 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

2013-03-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-02-12

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

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