Clinical Trials Register

Summary
EudraCT Number:	2016-004967-38
Sponsor's Protocol Code Number:	M16-135
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-06-08
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

Italy - Italian Medicines Agency

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 Na¿ve Adults with Chronic Hepatitis C Virus (HCV) Genotype 1, 2, 4, 5 or 6 Infection and Compensated Cirrhosis

Sperimentazione Multicentrica in Aperto a Braccio Singolo per Valutare l¿Efficacia e la Sicurezza di Glecaprevir (GLE) / Pibrentasvir (PIB) in Soggetti Adulti Affetti da Infezione Cronica da Virus dell¿Epatite C (HCV) di Genotipo 1, 2, 4, 5 o 6 con Cirrosi Compensata e Na¿ve Rispetto al Trattamento.

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

N.A.

A.4.1

Sponsor's protocol code number

M16-135

A.5.4

Other Identifiers

Name:

N.D.

Number:

N.D.

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 Road
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	00441628561090
B.5.5	Fax number	00441628461153
B.5.6	E-mail	eu-clinical-trials@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.3.9.4	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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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

E.1.1.1

Medical condition in easily understood language

HCV Genotype 1, 2, 4, 5 or 6 in treatment na¿ve subjects with compensated cirrhosis

HCV di Genotipo 1,2,4,5 o 6 in soggetti con cirrosi compensata e na¿ve rispetto al trattamento

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	100000004848

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 na¿ve 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 na¿ve adults with chronic HCV GT 1, 2, 4, 5 or 6 infection and compensated cirrhosis.

¿ Dimostrare la non inferiorit¿ dei tassi di risposta SVR12 per il trattamento della durata di 8 settimane con il regime combinato glecaprevir/pibrentasvir rispetto al tasso SVR12 storico ottenuto dal trattamento della durata di 12 settimane con glecaprevir/pibrentasvir in adulti affetti da infezione cronica da virus HCV di genotipo 1, 2, 4, 5 o 6 e cirrosi compensata che sono na¿ve al trattamento. L¿obiettivo primario di efficacia sar¿ valutato in maniera trasversale per tali genotipi nella popolazione PP (per protocol).
¿ Valutare la sicurezza del trattamento della durata di 8 settimane con il regime combinato glecaprevir/pibrentasvir in soggetti adulti affetti da infezione cronica da virus HCV di genotipo 1, 2, 4, 5 o 6 e cirrosi compensata, na¿ve al trattamento.

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 na¿ve 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.

- Dimostrare la non inferiorit¿ dei tassi di risposta SVR12 per il trattamento della durata di 8 settimane con il regime combinato glecaprevir/pibrentasvir rispetto al tasso SVR12 storico ottenuto dal trattamento della durata di 12 settimane con glecaprevir/pibrentasvir in adulti affetti da infezione cronica da virus HCV di genotipo 1, 2, 4, 5 o 6 e cirrosi compensata nella popolazione Intention-to-Treat (ITT).
- Valutare la percentuale di soggetti che manifestano fallimento virologico durante il trattamento (on-treatment virologic failure, OTVF) in maniera trasversale per i genotipi (nella popolazione ITT).
- Valutare la percentuale di soggetti con recidiva post-trattamento rilevata in maniera trasversale per i genotipi (nella popolazione ITT).

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. Soggetti di ambo i sessi, di età pari o superiore a 18 anni al momento dello Screening;
2. Infezione da HCV di genotipo 1, 2, 4, 5 o 6 confermata dai risultati degli esami di laboratorio eseguiti allo Screening;
3. Positività plasmatica per anticorpi anti-HCV e carica virale HCV RNA = 1000 UI/mL allo Screening;
4. Soggetti naïve rispetto al trattamento con qualsiasi medicinale anti-HCV approvato o sperimentale;
5. Soggetti per cui sia disponibile evidenza di cirrosi, con un punteggio 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 ofsmall 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
6. History of suspected or confirmed hepatocellular carcinoma.

1. Soggetto di sesso femminile in gravidanza, in allattamento o che intenda iniziare una gravidanza nel corso della sperimentazione o nei circa 30 giorni dopo l’ultima dose del medicinale sperimentale;
2.Qualsiasi evidenza clinica attuale o pregressa di cirrosi scompensata, compresa qualsiasi evidenza attuale o pregressa di Child-Pugh B o C, encefalopatia epatica oppure emorragia da varici, evidenza radiografica di ascite di grado lieve oppure uso empirico di lattulosio/rifaximina. L’uso di betabloccanti non rappresenta un criterio di esclusione;
3. Presenza attuale di infezione da HBV oppure HIV rilevata durante il periodo di Screening , definita come:
• Positività per HBsAg, oppure;
• HBV DNA > LLOQ in soggetti con positività isolata dell’anti-HBc (ovvero, negatività per HBsAg ed Anti- HBs), oppure;
• Positività per HIV Ab (anticorpi anti-HIV).
4. Infezione da virus HCV di genotipo 3 confermata dal laboratorio centrale nel corso dello Screening oppure presenza di coinfezione con più di un genotipo del virus HCV;
5. Risultati delle analisi di laboratorio che indicano una delle seguenti alterazioni:
• Alanina aminotransferasi ALT > 10 × ULN
• Aspartato aminotransferasi AST > 10 × ULN
• Bilirubina Totale > 3,0 mg/dl
• Clearance della creatinina (CrCl calcolata mediante formula di Cockcroft-Gault) < 50 ml/min
• Albumina < 2,8 mg/dl
• Emoglobina < 10 g/dl
• Piastrine < 50.000 cell/mm3
6. Storia di sospettato o confermato carcinoma epatocellulare

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.

L’obiettivo primario di efficacia consiste nella percentuale di soggetti che raggiungono la risposta SVR12 (HCV RNA < LLOQ 12 settimane dopo l'ultima dose attuale di farmaco sperimentale) in maniera trasversale nei genotipi.

E.5.1.1

Timepoint(s) of evaluation of this end point

12 weeks following the last dose of study drug

12 settimane dopo l'ultima dose attuale di farmaco sperimentale

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.

- Tassi di SVR12 (HCV RNA< LLOQ 12 settimane dopo l'ultima dose attuale di farmaco sperimentale) per i soggetti nella popolazione Intention-to-Treat (ITT).
- Percentuale di soggetti che manifestano fallimento virologico durante il trattamento.
- Percentuale di soggetti con recidiva post-trattamento.

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 settimane dopo l'ultima dose di farmaco sperimentale per l'end point secondario 1 e 2; 24 settimane dopo l'ultima dose di farmaco sperimentale per l'end point secondario 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

Information not present in EudraCT

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

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:

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

Nessuno

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

2017-07-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-06-14

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

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