Clinical Trials Register

Summary
EudraCT Number:	2016-001536-36
Sponsor's Protocol Code Number:	EARLY-HEP-C
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2016-07-08
Trial 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

2016-001536-36

A.3

Full title of the trial

Efficacy of GZR/EBR in Early Chronic Hepatitis C in HIV/HCV co-infected patients

Estudio abierto de fase III para evaluar la eficacia y la seguridad del tratamiento con Grazoprevir+Elbasvir para la hepatitis C crónica reciente en el paciente coinfectado VIH/VHC.

A.3.1

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

Efficacy of GZR/EBR in Early Chronic Hepatitis C in HIV/HCV co-infected patients

Estudio abierto de fase III para evaluar la eficacia y la seguridad del tratamiento con Grazoprevir+Elbasvir para la hepatitis C crónica reciente en el paciente coinfectado VIH/V

A.3.2

Name or abbreviated title of the trial where available

EARLY HEP-C

A.4.1

Sponsor's protocol code number

EARLY-HEP-C

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	Fundació Clínic per a la Recerca Biomèdica
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	MSD
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	CTU CLINIC (Clinical Trial Unit)
B.5.2	Functional name of contact point	Farmacologia clinica
B.5.3	Address:
B.5.3.1	Street Address	Rosello 138
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08036
B.5.3.4	Country	Spain
B.5.4	Telephone number	+349322754009838
B.5.5	Fax number	+34932279877
B.5.6	E-mail	acruceta@clinic.ub.es

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	Zepatier(Tablets: 50 mg elbasvir and 100 mg grazoprevir)
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme Limited. Herford Road, Hoddesdon Hertforside EN11 9BU Reino Unido
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	zepatier tablets
D.3.4	Pharmaceutical form	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	Elbasvir
D.3.9.3	Other descriptive name	ELBASVIR
D.3.9.4	EV Substance Code	SUB174125
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	Grazoprevir
D.3.9.3	Other descriptive name	GRAZOPREVIR
D.3.9.4	EV Substance Code	SUB174126
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	100
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

Early Chronic Hepatitis C in HIV/HCV co-infected patients

Hepatitis C crónica en pacientes coinfectados por el HIV

E.1.1.1

Medical condition in easily understood language

Early Chronic Hepatitis C in HIV/HCV co-infected patients

Hepatitis C crónica en pacientes coinfectados por el HIV

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	19.0
E.1.2	Level	LLT
E.1.2	Classification code	10065949
E.1.2	Term	HCV coinfection
E.1.2	System Organ Class	100000004862

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	LLT
E.1.2	Classification code	10068341
E.1.2	Term	HIV-1 infection
E.1.2	System Organ Class	100000004862

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

1.- Evaluate the efficacy of 12 or 8 weeks treatment with Grazoprevir + Elbasvir in Early Chronic Hepatitis C GT1,4 in HIV co-infected patients

2. Evaluate the safety and tolerability of Grazoprevir + Elbasvir in HIV-HCV co-infected patients

1- Evaluar la eficacia de 8-12 semanas de rtratamiento con Grazoprevir+Elbasvir en pacientes con hepatitis crónica reciente GT1,4 coinfectados por el HIV

2- Evaluar la seguridad y tolerabilidad de Grazoprevir+Elbasvir en coinfectados por los virus HIV+VHC

E.2.2

Secondary objectives of the trial

1.- Evaluate the reinfection rate during 1 year of follow-up
2. - Evaluate the emergence of viral resistance-associated variants (RAV) resistant to MK-5172 and MK-8742.

1- Evaluar la reinfección del VHC tras un año de tratamiento
2- Evaluar las mutaciones resistentes de los pacientes tratados con MK-5172 y MK-8742.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• ≥18 years of age
• Patients with early chronic hepatitis C (Genotype 1 or 4) which is defined as chronic hepatitis C with known episode of AHC within the last 4 years including those who failed to PEG/RBV or those who never received therapy for AHC. AHC infection is diagnosed on the basis of documented HCV-RNA positivity (> 10.000 IU/mL) and anti-HCV seroconversion.
• No history of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs/symptoms of advanced liver disease
• Have liver disease staging assessment as follows: Fibroscan performed within 3 previous months of Day 1 of this study showing result <8 kPa
• Be HIV-1 infected, documented by any licensed rapid HIV test and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 p24 antigen, or plasma HIV-1 RNA viral load.
• Be on stable HIV Antiretroviral Therapy (ART) for at least 8 weeks prior to study entry using a dual NRTI backbone of tenofovir or abacavir and either emtricitabine or lamivudine PLUS raltegravir, or dolutegravir.

• ≥ 18 años de edad
• Los pacientes deben presentar una hepatitis cónica C (genotipo 1 o 4) reciente; que se define por haber padecido un episodio conocido previo de hepatitis aguda C en los últimos 4 años, incluyendo aquellos que fracasaron en PEG / RBV o aquellos que nunca recibieron terapia para la hepatitis aguda C (HAC). La HAC se diagnostica mediante la documentación de elevación de transaminasas, seroconversión de los anti-VHC y presencia de un RNA-VHC positivo.
• No existir antecedentes de ascitis, varices esofágicas sangrantes, encefalopatía hepática, u otros signos / síntomas de enfermedad hepática avanzada
• Disponer de una evaluación de la fibrosis hepática que presenta el paciente mediante un Fibroscan realizado dentro de los 3 meses anteriores al Día 1 del estudio con un resultado que sea <8 kPa
• Ser portador de una infección por el VIH-1 bien documentada por técnicas microbiológicas (prueba de anticuerpos y estudio en plasma de carga viral (RNA-VIH) con buen control viral (CV-VIH indetectable mantenida un mínimo de tres meses previos al inicio del estudio)
• Estar bajo terapia antirretroviral (ART) estable para el VIH durante al menos las 8 semanas anteriores al inicio del estudio con una pauta que contengan 2 fármacos inhibidores de la trancriptasa inversa análogos de nucleósidos (tenofovir o abacavir y lamivudina o emtricitabina) asociado a raltegravir o dolutegravir.

E.4

Principal exclusion criteria

• < 18 years of age
• Patients with chronic hepatitis C genotypes other than 1 or 4.
• History of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs/symptoms of advanced liver disease
• Have liver disease staging assessment as follows: Fibroscan performed within 3 previous months of Day 1 of this study showing result > 8kPa
• Not be HIV-1 infected, documented by any licensed rapid HIV test and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 p24 antigen, or plasma HIV-1 RNA viral load.
• Due to known or suspected drug-drug interactions, for the purpose of this study, the use of Non Nucleoside Reverse Transcriptase Inhibitors, boosted Integrase Inhibitors or Protease Inhibitors against HIV will be not allow.

• <18 años de edad
• Pacientes con hepatitis C crónica genotipos diferentes de 1 o 4.
• Historia clínica de enfermedad hepática avanzada descompensada
• Fibroscan basal con un valor > 8 kPa
•No estar coinfectado por el VIH-1
•Uso de una pauta de terapia antirretroviral que contenga fármacos no permitidos en el estudio tales cómo inhibidores de la transcriptasa inversa no análogos de los nucleósidos o inhibidores de la proteasa contra el VIH

E.5 End points

E.5.1

Primary end point(s)

1.- Evaluate the efficacy of 12 or 8 weeks treatment with Grazoprevir + Elbasvir in Early Chronic Hepatitis C GT1,4 in HIV co-infected patients with Viral load hepatitis c (HCV) post treatment
2. Evaluate the safety and tolerability of Grazoprevir + Elbasvir in HIV-HCV co-infected patients

1. porcentage de indetectabilidad para la carga viral del virus hepatitis C tras 8-12 semanaas de tratamiento
2. Evaluar la seguridad y tolerabilidad de Grazoprevir + Elbasvir en pacientes coinfectados por VIH y VHC mediante el control de los efectos adversos y la retirada de la medicación por efectos adversos relacionados con los fármacos del estudio,

E.5.1.1

Timepoint(s) of evaluation of this end point

1- with Viral load hepatitis c (HCV) post treatment
2- Susars, SAEs , death

1- porcentage de pacientes con cargas para VHC indetectables tras el tratamiento
2- No de efectos adversos graves provocados por la medicación del estudio, efectos que provoquen abandono de tratamiento, muertes , SAEs

E.5.2

Secondary end point(s)

1.- Evaluate the reinfection rate during 1 year of follow-up (viral load VHC (w 4, 8,12,24,48 post tratment)
2. -Evaluate the emergence of viral resistance-associated variants (RAV) resistant to MK-5172 and MK-8742.

1- evaluar la reinfección mediante cargas virales VHC (semanas 4, 8 ,12, 24 ,48 post tratamiento)
2. evaluar la aparición de mutaciones resistentes a la medicación del estudio ( MK-5172 y MK-8742)

E.5.2.1

Timepoint(s) of evaluation of this end point

N/A

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

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

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

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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:

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.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)

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

2016-08-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-07-29

P. End of Trial
P.	End of Trial Status	Ongoing

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