Clinical Trials Register

Summary
EudraCT Number:	2015-002012-33
Sponsor's Protocol Code Number:	M15-461
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:	2015-07-31
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

2015-002012-33

A.3

Full title of the trial

An Open-Label Study to Evaluate the Safety and Efficacy of Ombitasvir/Paritaprevir/Ritonavir With or Without Dasabuvir in Adults With Genotype 1a or Genotype 4 Chronic Hepatitis C Virus (HCV) Infection, With Severe Renal Impairment or End-Stage Renal Disease (RUBY-II)

Estudio abierto para evaluar eficacia y seguridad de Ombitasvir/Paritaprevir/Ritonavir con o sin Dasabuvir en adultos con infección crónica por el virus de la Hepatitis C (VHC) de los genotipos 1a o 4 con insuficiencia renal grave o nefropatía terminal (RUBY-II)

A.3.1

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

An Open-Label Study to Evaluate the Safety and Efficacy of Ombitasvir/Paritaprevir/Ritonavir with or without Dasabuvir in Adults with Genotype 1a or Genotype 4 Chronic Hepatitis C Virus (HCV) Infection, with Severe Kidney Impairment or End-Stage Kidney Disease (RUBY-II)

A.4.1

Sponsor's protocol code number

M15-461

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
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	+441628672566
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	Yes
D.2.1.1.1	Trade name	Ombitasvir/Paritaprevir/Ritonavir 12.5 mg/75 mg/50 mg film-coated tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	AbbVie Ltd
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	Ombitasvir/Paritaprevir/Ritonavir
D.3.2	Product code	ABT-267/ABT-450/r
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	OMBITASVIR
D.3.9.1	CAS number	1456607-70-7
D.3.9.2	Current sponsor code	OMBITASVIR (ABT-267)
D.3.9.3	Other descriptive name	OMBITASVIR
D.3.9.4	EV Substance Code	SUB131058
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.3.8 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	PARITAPREVIR (ABT-450)
D.3.9.4	EV Substance Code	SUB166312
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.3.11 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	Dasabuvir 250 mg film-coated tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	Abbvie Ltd.
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	Dasabuvir
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	Dasabuvir (ABT-333)
D.3.9.3	Other descriptive name	DASABUVIR SODIUM
D.3.9.4	EV Substance Code	SUB131060
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.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 Hepatitis C infection

Infección Cronica por Hepatitis C

E.1.1.1

Medical condition in easily understood language

Chronic Hepatitis C infection

Infección Cronica por 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	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 objective of this study is to assess the safety and efficacy (the percentage of subjects achieving a 12-week sustained virologic response, SVR12 [HCV ribonucleic acid (RNA) < lower limit of quantification (LLOQ) 12 weeks following treatment]) of co-formulated ombitasvir, paritaprevir and ritonavir (ombitasvir/paritaprevir/ritonavir) with dasabuvir for 12 weeks in treatment-naïve subjects with HCV genotype 1a infection, or without dasabuvir for 12 weeks in treatment naïve subjects with HCV genotype 4 infection, Subjects are non-cirrhotic subjects and have severe renal impairment (pre-dialysis) or end-stage renal disease (on hemodialysis or peritoneal dialysis).

El objetivo primario de este studio es asegurar la seguridad y eficacia (porcentaje de sujetos que alcanzan una respuesta virologica sostenida a las 12 semanas, RVS12 [ácido ribonucleico (ARN) del VHC < límite inferior de cuantificación (LLOQ) a las 12 semanas de tratamiento]) de la coformulación ombitasvir, paritaprevir y ritonavir (ombitasvir/paritaprevir/ritonavir) con dasabuvir durante 12 semanas en pacientes infectados por VHC genotipo 1a que no han recibido tratamientos previos, o sin dasabuvir durante 12 semanas en pacientes infectados por VHC genotipo 4 sin haber recibido tratamientos previos. Los sujetos son no-cirróticos y tienen fallo renal agudo (pre-diálisis) o enfermedad renal en estado terminal (en hemodiálisis o diálisis peritoneal).

E.2.2

Secondary objectives of the trial

The secondary objectives of this study are to assess the number and percentage of subjects with virologic failure during treatment and the percentage of subjects with relapse post-treatment (PT).

Los objetivos secundarios de este estudio consisten en establecer el número y porcentaje de pacientes con recaída virológica durante el tratamiento y el porcentaje de sujetos que recaen postratamiento (PT).

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

1. Optional pharmacogenetic DNA Analysis
2. Optional Intensive pharmacokinetic assessment

1. Análisis farmacogenético de DNA opcional
2. Ensayo farmacocinético seriado opcional

E.3

Principal inclusion criteria

1. Chronic HCV infection.
2. Screening laboratory result indicating either HCV genotype 1a or genotype 4 infection.
3. Subject has never received antiviral treatment for hepatitis C infection.
4. Estimated Glomerular Filtration Rate (eGFR) < 30 mL/min/1.73 m2 as estimated by the MDRD method
5. No evidence of liver cirrhosis.
6. Females must be post-menopausal for more than 2 years or surgically sterile or practicing acceptable forms of birth control

1. Infección crónica de VHC.
2. Resultados de laboratorio en la selección indicando infección VHC por genotipo 1a o 4.
3. Sujetos que nunca hayan recibido tratamiento antiviral para la infección por hepatitis C.
4. Tasa estimada de filtrado glomerular (eGFR) <30 ml/min/1,73m2 calculada mediante el método MDRD.
5. Sin evidencias de cirrhosis hepatica.
6. Mujeres posmenopáusicas durante más de 2 años o ser estériles quirúrgicamente o practicar métodos aceptables de control de natalidad.

E.4

Principal exclusion criteria

1. Women who are pregnant or breastfeeding.
2. Positive test result for Hepatitis B surface antigen (HbsAg) or anti-Human immunodeficiency virus antibody (HIV Ab)
3. Clinically significant abnormalities or co-morbidities, other than HCV infection that make the subject an unsuitable candidate for this study or to receive ombitasvir/paritaprevir/ritonavir or dasabuvir.
4. Any prior antiviral therapy for HCV, including investigational or commercially approved agents.
5. Any current or past clinical evidence of cirrhosis.

1. Mujeres embarazadas o en situación de lactancia.
2. Resultado positivo para el test de detección de antígeno superficie de Hepatitis B (HbsAg) o presencia de anticuerpos frente al virus de la inmunodeficiencia humana (Ab VIH).
3. Anomalías o comorbilidades clínicamente significativas, diferentes de VHC que hacen que el sujeto no pueda participar en este estudio o recibir ombitasvir/paritaprevir/ritonavir o dasabuvir.
4. Cualquier terapia antiviral previa frente al VHC, incluídos agentes aprobados comercialmente o en investigación.
5. Cualquier evidencia clínica actual o pasada de cirrosis.

E.5 End points

E.5.1

Primary end point(s)

Safety and Efficacy (Virologic response at SVR12 )

Seguridad y eficacia (respuesta virológica a las 12 semanas, RVS12).

E.5.1.1

Timepoint(s) of evaluation of this end point

Interim analysis after all subjects in a treatment arm completed the post-treatment of week 12 or prematurely discontinued from the study.

Análisis parcial de todos los sujetos en un brazo de tratamiento que hayan completado el periodo pos tratamiento de 12 semanas o hayan interrumpido de manera prematura el estudio.

E.5.2

Secondary end point(s)

Number and percentage of subjects with Virologic failure during treatment and the number and percentage of subjects relapse post-treatment.

Número y porcentaje de sujetos que manifiestan recaída virológica durante el tratamiento y número y porcentaje de sujetos que recaen en el pos tratamiento.

E.5.2.1

Timepoint(s) of evaluation of this end point

End of the study

Final 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

Yes

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

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)

Information not present in EudraCT

E.8.2.2

Placebo

Information not present in EudraCT

E.8.2.3

Other

Information not present in EudraCT

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

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

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 will receive ombitasvir/paritaprevir/ritonavir, and dasabuvir continue on study treatment throughout the Treatment Period for 12 weeks or until premature discontinuation of study drug, followed by a 24 week Post-Treatment Period. At the subject's last study visit, the investigator will discuss the appropriate subsequent treatment with the subject.
AbbVie will not provide commercially available drug or any other therapy once the subject's participation is concluded.

Los sujetos recibirán ombitasvir/paritaprevir/ritonavir,y dasabuvir durante el periodo de tratamiento del estudio de 12 sem de duración o hasta que lo interrumpa de manera prematura, seguido de un periodo de 24 sem postratamiento. Durante la última visita del sujeto, el investigador decidirá el adecuado tratamiento a seguir con el paciente. AbbVie no proveerá los fármacos disponibles comercialmente ni cualquier otra terapia una vez que el sujeto haya finalizado su participación en el estudio.

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

2015-09-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-09-08

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-12-05

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