Clinical Trials Register

Summary
EudraCT Number:	2012-005143-24
Sponsor's Protocol Code Number:	M14-004
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:	2015-05-08
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

2012-005143-24

A.3

Full title of the trial

A Multipart, Open-label Study to Evaluate the Safety and Efficacy of Ombitasvir/Paritaprevir/Ritonavir With and Without Dasabuvir Coadministered With and Without Ribavirin in Adults With Genotype 1 or 4 Chronic Hepatitis C Virus Infection and Human Immunodeficiency Virus, Type 1 Coinfection (TURQUOISE-I)

Estudio abierto, con varias partes, para evaluar la seguridad y la eficacia del tratamiento con ombitasvir/paritaprevir/ritonavir con y sin dasabuvir administrado conjuntamente con y sin ribavirina en adultos con infección crónica por el virus de la hepatitis C del genotipo 1 o 4 y coinfección por el virus de la inmunodeficiencia humana del tipo 1 (TURQUOISE-I)

A.3.1

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

A two part, open-label study to evaluate the safety and effectiveness ombitasvir/paritaprevir/ritonavir with and without dasabuvir given with or without a drug called ribavirin in people with both hepatitis C virus genotype 1 or 4 infection and human immunodeficiency virus, type 1 infection.

A.4.1

Sponsor's protocol code number

M14-004

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01939197

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	AbbVie Deutschland GmbH & Co. KG
B.1.3.4	Country	Germany
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	AbbVie 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	AbbVie Ltd.
B.5.2	Functional name of contact point	EU Clinical Trials Helpdesk
B.5.3	Address:
B.5.3.1	Street Address	Abbott House, Vanwall Business Park, Vanwall Road,
B.5.3.2	Town/ city	Maidenhead, Berkshire
B.5.3.3	Post code	SL6 4XE
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+34901200103
B.5.5	Fax number	+441628644330
B.5.6	E-mail	abbvie_reec@abbvie.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	ABT-450/r/ABT-267
D.3.2	Product code	ABT-450/r/ABT-267
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	Paritaprevir
D.3.9.1	CAS number	1456607-71-8
D.3.9.2	Current sponsor code	ABT-450
D.3.9.3	Other descriptive name	ABT-450
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	75
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	RITONAVIR
D.3.9.1	CAS number	155213-67-5
D.3.9.2	Current sponsor code	RITONAVIR
D.3.9.4	EV Substance Code	SUB10342MIG
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	50
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Ombitasvir
D.3.9.1	CAS number	1456607-70-7
D.3.9.2	Current sponsor code	ABT-267
D.3.9.3	Other descriptive name	ABT-267
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	12.5
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	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	ABT-333
D.3.2	Product code	ABT-333
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	Dasabuvir
D.3.9.1	CAS number	1456607-55-8
D.3.9.2	Current sponsor code	ABT-333
D.3.9.3	Other descriptive name	ABT-333
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	250
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.2.5	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	Ribavirin
D.3.2	Product code	Ribavirin
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.3.9.2	Current sponsor code	RIBAVIRIN
D.3.9.3	Other descriptive name	RIBAVIRIN
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
Human Immunodeficiency Virus Infection
Chronic Hepatitis C
Compensated Cirrhosis and Non-cirrhotics

Infección por Virus de la Hepatitis C
Infeccion por virus de inmunodeficiencia humana
Hepatitis C crónica
Cirrosis compensada y no cirroticos.

E.1.1.1

Medical condition in easily understood language

Hepatitis C Virus Infection
Human Immunodeficiency Virus Infection

Infección por Virus de la Hepatitis C
Infeccion por virus de inmunodeficiencia humana

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	18.0
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 assess the safety of ABT-
450/r/ABT-267 with and without ABT-333 coadministered with and
without RBV for 12 and 24 weeks in HCV GT 1- or 4-infected subjects
with HIV-1 coinfection and to evaluate the percentage of subjects
achieving SVR12 (HCV RNA < lower limit of quantification [LLOQ] 12
weeks following treatment). These objectives will be assessed
separately within each part of the study.
For Part 1a, the 12- and 24-week treatment arms will be assessed
separately; For Part 1b, the darunavir (DRV) QD and BID arms will be assessed separately as well as in combination; And for Part 2, the GT 1-infected subjects will be assessed separately from the GT 4-infected subjects, and the percentage of GT 1-infected subjects achieving SVR12 will be compared to a threshold based on the historical SVR12 rate of sofosbuvir (SOF) plus ribavirin (RBV).

Los objetivos principales del estudio son evaluar la seguridad del tratamiento con ABT 450/r/ABT-267 con y sin ABT-333 administrado conjuntamente con y sin RBV durante 12 y 24 semanas en pacientes con infección por el VHC del genotipo 1 o 4 y coinfección por el VIH-1 y evaluar el % de pacientes que alcanzan la RVS12 (ARN del VHC < límite inferior de cuantificación [LIC] 12 semanas después del tratamiento). Estos objetivos se evaluarán por separado en cada parte del estudio. En la parte 1a se evaluarán por separado los grupos de tratamiento de 12 y 24 semanas. En la parte 1b se evaluarán los grupos de darunavir DRV una vez al día y dos veces al día por separado y combinados. En la parte 2 se evaluará a los pacientes infectados con el VHC GT1 por separado de los infectados por el VHC-GT4, y % de pacientes infectados con el GT1 que logran la RVS12 se comparará con un umbral calculado a partir de la tasa histórica de RVS12 obtenida con el tratamiento con sofosbuvir (SOF) más RBV.

E.2.2

Secondary objectives of the trial

The secondary objectives of this study are to assess the percentage of subjects with on-treatment HCV virologic failure, the percentage of subjects with HCV virologic relapse, and the percentage of subjects with plasma HIV-1 viral suppression at the end of treatment and at Post-Treatment Week 12 within each part of the study; and to compare the SVR12 rates between the 12-week (Arm A) and 24-week (Arm B) treatment arms in Part 1a of the study; between the DRV QD (Arm C) and BID (Arm D) arms in Part 1b of the study; and between the GT 1b cirrhotic subjects treated with RBV (Arm G) and without RBV (Arm F) in Part 2 of the study.

Los objetivos secundarios del estudio son evaluar el porcentaje de pacientes que presentan fracaso virológico frente al VHC durante el tratamiento, el porcentaje de pacientes con recidiva virológica del VHC y el porcentaje de pacientes con supresión viral del VIH-1 en plasma al final del tratamiento y en la semana 12 posterior al tratamiento en cada parte del estudio; y comparar las tasas de RVS12 entre:
? los grupos de tratamiento de 12 semanas (grupo A) y 24 semanas (grupo B) de la parte 1a;
? los grupos de DRV una vez al día (grupo C) y dos veces al día (grupo D) de la parte 1b;
? y los pacientes con infección por el VHC-GT1b y cirrosis tratados con RBV (grupo G) y sin RBV (grupo F) en la parte 2 del estudio.

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

Both substudies are described in the M14-004 Protocol Amendment 3 (05 Mar 2015).
Specific purposes of the optional pharmacogenetic and pharmacogenomic substudies include:
?identifying genetic reasons why certain people respond differently to ABT-450/r/ABT-267 and ABT-333 (if applicable);
?finding out more information about how ABT-450/r/ABT-267 and ABT-333 (if applicable) work;
?finding out information needed for research, development, and regulatory approval for tests to predict response to ABT-450/r/ABT-267 and ABT-333 (if applicable).

Ambos subestudios estan descritos en la enmienda 3 al protocol M14-004 (05 Mar 2015).
Los propósitos específicos de los subestudios opcionales farmacogenetico y farmacogenomico incluyen:
- identificar factores genéticos que contribuyan a explicar por qué ciertas personas responden de forma distinta a ABT-450/r/ABT-267 y ABT-333 (si aplica).
- Obtener más información sobre como ABT-450/r/ABT-267 y ABT-333(si aplica) actuan.
- Obtener más información necesaria para la investigación, desarrollo y aprobaciones regulatorias de pruebas que predigan la respuesta a ABT-450/r/ABT-267 y ABT-333(si aplica).

E.3

Principal inclusion criteria

1. Male or female at least 18 years of age at the time of screening.
2. Chronic HCV infection defined as: Positive anti-HCV Ab or HCV RNA > 1,000 IU/ml at screening.
3. Plasma HIV-1 RNA < 40 copies/mL during screening using Abbott RealTime HIV-1 assay.
4. On a stable, qualifying HIV-1 antiretroviral (ART) regimen for at least 8 weeks prior to screening. The HIV-1 ART regimen must include at least one of the following ARV agents:
? Atazanavir (ATV) PO QD coadministered with ritonavir (RTV) PO QD
? Darunavir (DRV) PO QD coadministered with ritonavir (RTV) PO QD (for all subjects in Part 1b and genotype 4 subjects in Part 2 only)
? Raltegravir (RAL) PO BID
? Dolutegravir (DTG) PO QD or PO BID (Part 2 only)

1. Varones o mujeres de 18 o más años de edad en el momento de la selección.
2. Infección crónica por el VHC en el momento de la selección, definida por: Resultado positivo en el análisis de anticuerpos (Ac) anti-VHC ó ARN del VHC > 1000 UI/ml en la selección.
3. ARN del VIH-1 en plasma < 40 copias/ml durante la selección con el análisis Abbott RealTime HIV de Abbott.
4. Estar recibiendo TAR contra el VIH-1 con una pauta válida y estable durante al menos 8 semanas antes de la selección. La pauta de TAR contra el VIH-1 debe incluir al menos uno de los ARV siguientes:
a. Atazanavir (ATV) oral una vez al día administrado conjuntamente con ritonavir (RTV) oral una vez al día.
b. Darunavir (DRV) oral una vez al día administrado conjuntamente con ritonavir (RTV) oral una vez al día (para todos los pacientes de la parte 1b y solo pacientes con infección por el VHC-GT4 en la parte 2).
c. Raltegravir (RAL) oral dos veces al día.
d. Dolutegravir (DTG) oral una vez al día o dos veces al día (Solo parte 2).

E.4

Principal exclusion criteria

1. Positive test result at screening for Hepatitis B surface antigen (HBsAg).
2. Evidence of HCV genotype other than GT 1 or GT 4 during screening.
3. Receipt of any other investigational or commercially available anti-HCV agents (e.g., telaprevir, boceprevir, simeprevir, daclatasvir and ledipasvir) with the exception of interferon, (including pegIFN), SOF and RBV.
4. Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive ABT-450, ABT-267, ABT-333, ritonavir or RBV.
5. Chronic human immunodeficiency virus, type 2 (HIV-2) infection.

1. Resultado positivo en la prueba del antígeno de superficie del virus la hepatitis B (HBsAg) durante la selección.
2. Detección de genotipos del VHC distintos del 1 y el 4 durante la selección.
3. Tratamiento con cualquier otro fármaco contra el VHC, en investigación o comercializado (como telaprevir, boceprevir, simeprevir, daclatasvir y ledipasvir), excepto interferón (o pegIFN), SOF y RBV.
4. El investigador considera, por el motivo que sea, que el paciente no es un candidato adecuado para recibir ABT-450, ABT-267, ABT-333, ritonavir o RBV.
5. Infección crónica por el virus de la inmunodeficiencia humana de tipo 2 (VIH-2).

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is the percentage of subjects in GT 1 Analysis Group 1 in Part 2 achieving SVR12 (HCV RNA < LLOQ 12 weeks after the last actual dose of study drug) compared to the historical SVR12 rate for sofosbuvir plus RBV as reported in the PHOTON-1 study. The percentage of subjects achieving SVR12 will be calculated and a 2-sided 95% confidence interval (CI) of the percentage will be computed using the Wilson score method for the binomial proportion. The lower confidence bound of the 2-sided 95% Confidence Interval (LCB) for the percentage of subjects achieving SVR12 must exceed 74% to achieve non-inferiority.

El criterio de valoración principal de la eficacia es el porcentaje de pacientes del grupo de análisis del GT1 de la parte 2 que logran la RVS12 (ARN del VHC < LIC 12 semanas después de la última dosis real del fármaco del estudio) en comparación con la tasa histórica de RVS12 obtenida con el tratamiento con sofosbuvir más RBV que se indica en el estudio PHOTON-1. Se calculará el porcentaje de pacientes que consiguen la RVS12, cuyo intervalo de confianza (IC) del 95 % bilateral se determinará con el método de puntuación de Wilson para la proporción binomial. Para demostrar la ausencia de inferioridad, el límite inferior del IC del 95 % bilateral (LIIC) del porcentaje de pacientes que consiguen la RVS12 debe ser superior al 74 %.

E.5.1.1

Timepoint(s) of evaluation of this end point

12 weeks after the last dose of study drug

12 semanas tras la última dosis de medicación del estudio.

E.5.2

Secondary end point(s)

The secondary efficacy endpoints are:
1. The percentage of subjects in GT 1 Analysis Group 2 of Part 2 achieving SVR12 compared to the historical rate for sofosbuvir plus RBV. The LCB for the percentage of subjects achieving SVR12 must exceed 74% to achieve non-inferiority. The endpoint will be assessed only if success has been demonstrated for the primary endpoint of non-inferiority in the SVR12 rate compared to the historical rate.
2. The percentage of Part 1a subjects achieving SVR12 in the 24-week treatment group compared to the 12-week treatment group using Fisher's exact test.
3. The percentage of subjects of Part 1b subjects achieving SVR12 in the DRV QD arm compared to the DRV BID arm using Fisher's exact test.
4. The percentage of Part 1b subjects achieving SVR12.
5. The percentage of Part 2 GT 1b cirrhotic subjects achieving SVR12 in Arm F (without RBV) compared to Arm G (with RBV) using Fisher's exact test.
6. The percentage of GT 4 subjects in Part 2 achieving SVR12 by arm and overall.
7. The percentage of subjects with on treatment HCV virologic failure during the Treatment Period for the 12-week and 24-week treatment arms in Part 1a, the DRV QD and BID arms as well as the set of all subjects in Part 1b, the GT 1 Analysis Group 1 in Part 2, the GT1 Analysis Group 2 in Part 2 (performed only if non-inferiority is demonstrated for the first secondary endpoint) as well as the GT 4 Analysis Group by arm and overall.
8. The percentage of subjects with HCV post-treatment relapse (analyses performed as described for secondary endpoint 7).
9. The percentage of subjects with plasma HIV-1 RNA suppression at end of treatment and Post Treatment Week 12 using the FDA Snapshot Algorithm (analyses performed as described for secondary endpoint 7). Comparison of the DRV QD and BID arms in Part 1b will be made using Fisher's exact test.
For each of the secondary endpoints, the percentages (with 2-sided 95% confidence intervals using the Wilson score method for the binomial proportion) will be calculated.

Los criterios de valoración secundarios de la eficacia son los siguientes:
1. Porcentaje de pacientes del grupo 2 de análisis del GT1 de la parte 2 que consiguen la RVS12 en comparación con la tasa histórica del tratamiento con sofosbuvir más RBV. Para alcanzar la ausencia de inferioridad, el LIIC del porcentaje de pacientes que consiguen la RVS12 debe ser superior al 74%. Este criterio de valoración solo se evaluará si se demuestra el éxito con el criterio de valoración principal de ausencia de inferioridad de la tasa de RVS12 en comparación con la tasa histórica.
2. Porcentaje de pacientes de la parte 1a que consiguen la RVS12 en el grupo de tratamiento de 24 semanas en comparación con el grupo de tratamiento de 12 semanas mediante la prueba exacta de Fisher.
3. Porcentaje de pacientes de la parte 1b que consiguen la RVS12 en el grupo de tratamiento de con DRV una vez al día en comparación con el grupo de tratamiento con DRV dos veces al día mediante la prueba exacta de Fisher.
4. Porcentaje de pacientes de la parte 1b que consiguen la RVS12.
5. Porcentaje de pacientes de la parte 2 con infección por el GT1b y cirrosis que consiguen la RVS12 en el grupo F (sin RBV) en comparación con el grupo G (con RBV) mediante la prueba exacta de Fisher.
6. Porcentaje de pacientes de la parte 2 con infección por el GT4 que consiguen la RVS12 por grupo y en total.
7. Porcentaje de pacientes con fracaso virológico frente al VHC durante el tratamiento en el período de tratamiento en los grupos de 12 y 24 semanas de la parte 1a, los grupos de DRV una vez al día y dos veces al día, el grupo de todos los pacientes de la parte 1b, el grupo 1 de análisis del GT1 de la parte 2, el grupo 2 de análisis del GT1 de la parte 2 (solo en caso de que se demuestre ausencia de inferioridad en cuanto al primer criterio de valoración secundario) y el grupo de análisis del GT4 por grupos y en total.
8. Porcentaje de pacientes con recidiva después del tratamiento contra el VHC (análisis efectuado conforme a lo descrito en el criterio de valoración secundario n.º 7).
9. Porcentaje de pacientes con supresión del ARN del VIH-1 en plasma al final del tratamiento y en la semana 12 del periodo posterior al tratamiento según el algoritmo instantáneo de la FDA (FDA Snapshot Algorithm) (análisis efectuado conforme a lo descrito en el criterio de valoración secundario n.º 7) La comparación de los grupos de DRV una vez al día y dos veces al día en la parte 1b se llevará a cabo con la prueba exacta de Fisher.

En todos los criterios de valoración secundarios se calcularán los porcentajes (y los intervalos de confianza bilaterales del 95% mediante el método de puntuación de Wilson para la proporción binomial).

E.5.2.1

Timepoint(s) of evaluation of this end point

Treatment Day 1 to end of treatment (week 12 or week 24) and end of treatment to 12 weeks after the last dose of study drug.

Tratamiento dia 1 hasta el final del tratamiento (12 semana o 24 semanas) y desde final de tratamiento hasta 12 semanas después de la última dosis de medicación 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

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

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

Yes

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

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

Canada

European Union

Mexico

New Zealand

Puerto Rico

Russian Federation

United States

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

Last Subject Last Visit

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:

290

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

105

F.4.2.2

In the whole clinical trial

320

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)

Upon completion of treatment, subjects are followed for 24 weeks after the last dose of study drug. Additional plans for treatment will be at the investigator's discretion

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

2015-07-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-07-10

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-10-25

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