Clinical Trials Register

Summary
EudraCT Number:	2016-004967-38
Sponsor's Protocol Code Number:	M16-135
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:	2017-09-18
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

2016-004967-38

A.3

Full title of the trial

A Single Arm, Open-label Study to Evaluate the Efficacy and Safety of Glecaprevir (GLE)/Pibrentasvir (PIB) in Treatment Naïve Adults with Chronic Hepatitis C Virus (HCV) Genotype 1, 2, 4, 5 or 6 Infection and Compensated Cirrhosis

Estudio abierto y de un solo grupo para evaluar la eficacia y la seguridad de glecaprevir (GLE)/pibrentasvir (PIB) en pacientes con infección crónica por el virus de la hepatitis C (VHC) de genotipo 1, 2, 4, 5 o 6 y cirrosis compensada no tratados previamente

A.3.1

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

A.4.1

Sponsor's protocol code number

M16-135

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	AbbVie House, Vanwall Business Park, Vanwall Rd
B.5.3.2	Town/ city	Maidenhead, Berkshire
B.5.3.3	Post code	SL6 4UB
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+34901 200 103
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	Glecaprevir/Pibrentasvir
D.3.2	Product code	ABT-493/ABT-530
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	Pibrentasvir
D.3.9.2	Current sponsor code	ABT-530
D.3.9.3	Other descriptive name	PIBRENTASVIR
D.3.9.4	EV Substance Code	SUB180955
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	40
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Glecaprevir
D.3.9.2	Current sponsor code	ABT-493
D.3.9.3	Other descriptive name	GLECAPREVIR
D.3.9.4	EV Substance Code	SUB180954
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

HCV

VCH

E.1.1.1

Medical condition in easily understood language

HCV Genotype 1, 2, 4, 5 or 6 in treatment naïve subjects with compensated cirrhosis

VHC Genotipo 1, 2, 4, 5 o 6 en sujetos no tratados previamente con cirrosis compensada

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	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10019752
E.1.2	Term	Hepatitis C virus (HCV)
E.1.2	System Organ Class	100000074171

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 demonstrate the non-inferiority of the SVR12 rates of 8 weeks of treatment with the glecaprevir/pibrentasvir combination regimen to the historical SVR12 rate of 12 weeks of treatment with the glecaprevir/pibrentasvir in treatment naïve adults with chronic HCV GT 1, 2, 4, 5 or 6 infection and compensated cirrhosis. The primary efficacy objective will be assessed across genotypes, in the Per-Protocol (PP) population.
To assess the safety of 8 weeks of treatment with the glecaprevir/pibrentasvir combination regimen in treatment naïve adults with chronic HCV GT 1, 2, 4, 5 or 6 infection and compensated cirrhosis.

Demostrar la ausencia de inferioridad de las tasas de RVS12 con 8 semanas de tratamiento con la pauta de combinación de glecaprevir/pibrentasvir con respecto a la tasa histórica de RVS12 con 12 semanas de tratamiento con glecaprevir/pibrentasvir en adultos con infección crónica por el VHC GT 1, 2, 4, 5 o 6 y cirrosis compensada no tratados previamente. El objetivo principal de eficacia se evaluará en los distintos genotipos en la población conforme al protocolo (PP).
Evaluar la seguridad de 8 semanas de tratamiento con la pauta de combinación de glecaprevir/pibrentasvir en adultos con infección crónica por el VHC GT 1, 2, 4, 5 o 6 y cirrosis compensada no tratados previamente.

E.2.2

Secondary objectives of the trial

To demonstrate the non-inferiority of the SVR12 rates of 8 weeks of treatment with the glecaprevir/pibrentasvir combination regimen to the historical SVR12 rate of 12 weeks of treatment with the glecaprevir/pibrentasvir in treatment naïve adults with chronic HCV GT 1, 2, 4, 5 or 6 infection and compensated cirrhosis based on in the intention-to-treat (ITT) population.
To assess the percentage of subjects with OTVF across genotypes in the intention-to-treat (ITT) population.
To assess the percentage of subjects with post-treatment relapse across genotypes in the intention-to-treat (ITT) population.

Demostrar la ausencia de inferioridad de las tasas de RVS12 con 8 semanas de tratamiento con la pauta de combinación de glecaprevir/pibrentasvir con respecto a la tasa histórica de RVS12 con 12 semanas de tratamiento con glecaprevir/pibrentasvir en adultos con infección crónica por el VHC GT 1, 2, 4, 5 o 6 y cirrosis compensada basada en población con intención de tratamiento.
Determinar el porcentaje de sujetos con OTVF en todos los genotipos en la población por intención de tratar (IT).
Determinar el porcentaje de sujetos con recaída post tratamiento en todos los genotipos en la población por intención de tratar (IT).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female, at least 18 years of age at time of Screening;
2. Screening laboratory result indicating HCV GT 1, 2, 4, 5 or 6 infection;
3. Positive plasma HCV antibody and HCV RNA viral load ≥ 1000 IU/mL at Screening;
4. Treatment-naïve to any approved or investigational anti-HCV medication;
5. Subject must be documented as cirrhotic, with a Child-Pugh score of ≤6.

1. Varones o mujeres con una edad mínima de 18 años en el momento de la selección;
2. Resultados analíticos en la selección indicativos de infección por el VHC GT1, 2, 4, 5 o 6
3. Positividad de los anticuerpos en plasma contra el VHC y carga del ARN del VHC ≥ 1000 UI/ml en la selección;
4. Ausencia de tratamiento previo con cualquier medicamento contra el VHC aprobado o experimental;
5. Presencia de cirrosis, con una puntuación de Child-Pugh ≤ 6.

E.4

Principal exclusion criteria

1. Female subject who is pregnant, breastfeeding or is considering becoming pregnant during the study, or for approximately 30 days after the last dose of study drug;
2. Any current or historical clinical evidence of decompensated cirrhosis, including any current or past evidence of Child-Pugh B or C classification, hepatic encephalopathy or variceal bleeding, radiographic evidence of small ascites, or empiric use of lactulose/rifaximin. The use of beta blockers is not exclusionary;
3. Current HBV or HIV infection on screening tests, defined as:
• A positive HBsAg, or;
• HBV DNA > LLOQ in subjects with isolated positive anti-HBc (i.e., negative HBsAg and Anti-HBs), or;
• A positive anti-human immunodeficiency virus antibody (HIV Ab).
4. HCV genotype performed by the central laboratory during screening indicating genotype 3 infection or co-infection with more than one HCV genotype;
5. Screening laboratory analyses showing any of the following abnormal laboratory results:
• Alanine aminotransferase ALT > 10 × ULN
• Aspartate aminotransferase AST > 10 × ULN
• Total Bilirubin > 3.0 mg/dL
• Calculated creatinine clearance (CrCl, Cockcroft-Gault method) of < 50 mL/min
• Albumin < 2.8 mg/dL
• Hemoglobin < 10 g/dL
• Platelets < 50,000 cells/mm3

1. Mujeres embarazadas o lactantes o que estén considerando quedarse embarazadas durante el estudio o en un plazo aproximado de 30 días después de la última dosis de la medicación del estudio;
2. Cualquier indicio actual o histórico de cirrosis descompensada, incluido cualquier indicio actual o pasado de clasificación B o C de Child-Pugh, encefalopatía hepática o varices hemorrágicas, signos radiológicos de pequeña ascitis o uso empírico de lactulosa/rifaximina. El uso de betabloqueantes no es excluyente;
3. Infección actual por el VHB o el VIH en las pruebas de selección, definida como:
• Positividad del HBsAg, o;
• ADN del VHB > LIC en los pacientes con anti-HBc positivo aislado (es decir, negatividad del HBsAg y anti-HBs), o;
• Positividad del anticuerpo contra el virus de la inmunodeficiencia humana (Ac VIH).
4. Genotipificación del VHC realizada por el laboratorio central durante la selección que indique infección por el genotipo 3 o infección concomitante por más de un genotipo del VHC;
5. Análisis de laboratorio de selección que deparen alguno de los siguientes resultados analíticos anómalos:
• Alanina aminotransferasa (ALT) > 10 x LSN
• Aspartato aminotransferasa (AST) > 10 x LSN
• Bilirrubina total > 3,0 mg/dl
• Aclaramiento de creatinina calculado (mediante el método de Cockcroft-Gault) < 50 ml/min
• Albúmina < 2,8 g/dl
• Hemoglobina < 10 g/dl
• Plaquetas < 50.000 células/mm3

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy variable is the percentage of subjects who achieve SVR12 (HCV RNA < LLOQ 12 weeks after the last actual dose of study drug) across genotypes.

La variable de eficacia primaria es el porcentaje de sujetos que alcanzan la RVS12 (RNA VHC < límite inferior de cuantificación a las 12 semanas después de la última dósis de la medicación en estudio) en todos los genotipos.

E.5.1.1

Timepoint(s) of evaluation of this end point

12 weeks following the last dose of study drug

12 semanas después de la última dósis de la medicación en estudio

E.5.2

Secondary end point(s)

- SVR12 (HCV RNA<LLOQ 12 weeks after the last actual dose of study drug) for the subjects in the Intention-to-Treat population.
- The percentage of subjects with HCV on-treatment virologic failure.
- The percentage of subjects with post-treatment HCV relapse.

- RVS12 (RNA VHC < límite inferior de cuantificación a las 12 semanas después de la última actual dósis de la medicación en estudio) para los sujetos por intención de tratar.
- Porcentaje de sujetos con fallo de tratamiento virológico contra VHC.
- Porcentaje de sujetos con recaída de VHC post tratamiento.

E.5.2.1

Timepoint(s) of evaluation of this end point

12 weeks following the last dose of study drug for Secondary Endpoint 1 and 2; 24 weeks following the last dose of study drug for Secondary Endpoint 3.

12 semanas después de la última dósis de la medicación en estudio para la finalidad secondaria 1 y 2; 24 semanas después de la última dósis de la medicación en estudio para la finalidad secundaria 3.

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

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

Canada

Israel

Mexico

Puerto Rico

Taiwan

United States

Vietnam

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

LSLV

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:

225

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

112

F.4.2.2

In the whole clinical trial

275

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)

None

Ninguno

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

2017-09-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-08-11

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-11-08

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