Clinical Trials Register

Summary
EudraCT Number:	2017-002221-37
Sponsor's Protocol Code Number:	PA-IT72-2012
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2020-11-04
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2017-002221-37

A.3

Full title of the trial

Glecaprevir/ pibrentasvir plus fixed-dose combination for 6 weeks in patients with acute hepatitis C virus: a pilot study.

Glecaprevir/ pibrentasvir in combinazione a dose fissa per 6 settimane in pazienti affetti da infezione acuta da HCV: uno studio pilota.

A.3.1

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

Six weeks of Glecaprevir/ pibrentasvir for patients with acute HCV infection.

Sei settimane di terapia con Glecaprevir/ pibrentasvir per i pazienti con epatite acuta da HCV.

A.3.2

Name or abbreviated title of the trial where available

Six weeks of Glecaprevir/ pibrentasvir for patients with acute HCV infection.

Glecaprevir/ pibrentasvir in combinazione a dose fissa per 6 settimane in pazienti affetti da infezi

A.4.1

Sponsor's protocol code number

PA-IT72-2012

A.5.4

Other Identifiers

Name:

A16-729

Number:

A16-729

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	AZIENDA OSPEDALIERA UNIVERSITARIA POLICLINICO “PAOLO GIACCONE” DI PALERMO
B.1.3.4	Country	Italy
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	Abbvie
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Policlinico Paolo Giaccone
B.5.2	Functional name of contact point	Servizio Informazione sulla Sperime
B.5.3	Address:
B.5.3.1	Street Address	Piazza delle Cliniche n.2
B.5.3.2	Town/ city	Palermo
B.5.3.3	Post code	90127
B.5.3.4	Country	Italy
B.5.4	Telephone number	3283096117
B.5.5	Fax number	0916552156
B.5.6	E-mail	vincenza.calvaruso@unipa.it

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	MAVIRET n.AIC 045445018/E
D.2.1.1.2	Name of the Marketing Authorisation holder	Abbvie S.r.l
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	[Glecaprevir/Pibrentasvir]
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.3.9.2	Current sponsor code	MAVIRET
D.3.9.3	Other descriptive name	Glecaprevir/Pibrentasvir
D.3.10	Strength
D.3.10.1	Concentration unit	MBq/mg megabecquerel(s)/milligram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	300120
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

Acute HCV infection

Epatite acuta da HCV

E.1.1.1

Medical condition in easily understood language

Acute HCV infection

Epatite acuta da HCV

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	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10047457
E.1.2	Term	Viral hepatitis C
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

Only few data are available on the management of acute HCV infection in the DAAs era. Therefore the optimal regimen and treatment duration of acute HCV infection require evaluation. The aim of the study is evaluate the efficacy and safety of the combinations of glecaprevir/pibrentasvir in the treatment of HCV acute hepatitis.

Sono attualmente disponibili solo dati limitati relativi alla gestione dell’infezione acuta da HCV nell’era degli agenti antivirali ad azione diretta (DAA), e pertanto è necessario determinare regime e durata del trattamento ottimali per l’infezione acuta da HCV. L’obiettivo della sperimentazione è quello di valutare l’efficacia e la sicurezza della combinazione glecaprevir/pibrentasvir nel trattamento dell’epatite acuta da virus dell’HCV.

E.2.2

Secondary objectives of the trial

Secondary endpoints included the following:
- safety and tolerability of glecaprevir plus pibrentasvir in this population
- virological responses after 2 weeks of treatment (very rapid virological response; vRVR), after 4 weeks of treatment (rapid virological response; RVR), at the end of treatment (end-of-treatment virological response; ETR), ALT level normalization at the end of treatment and at 12 weeks post- treatment follow-up;
- factors associated with SVR (genotype, baseline viral load, adherence…)

Gli endpoint secondari includono i seguenti:
- sicurezza e tollerabilità di glecaprevir più pibrentasvir in questa popolazione
- risposte virologiche dopo 2 settimane di trattamento (risposta virologica molto rapida [very rapid virological response] vRVR), dopo 4 settimane di trattamento (risposta virologica rapida [rapid virological response] RVR), alla fine del trattamento (risposta virologica alla fine del trattamento [end-of-treatment virological response] ETR), normalizzazione dei livelli di ALT alla fine del trattamento e al follow-up post trattamento a 12 settimane;
- fattori associati alla risposta SVR (genotipo, carica virale al baseline, aderenza al trattamento …)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Inclusion Criteria will be:
- Adult patients (=18 years);
- Presenting acute HCV infection (all genotypes);
- With or without HIV co-infection;
- Active or inactive drug users

Diagnosis of AHC:
Acute HCV infection was defined as either a documented seroconversion to HCV antibody positivity within the 4 months before screening, or known or suspected exposure to HCV within the 4 months before
screening with raised alanine aminotransferase concentration more than ten times the upper limit of
normal at screening or within a 4-week period before screening.

- Pazienti adulti (=18 anni);
- Pazienti con infezione acuta da HCV (qualsiasi genotipo);
- Pazienti con o senza co-infezione da HIV;
- Utilizzatori attivi o inattivi di droghe

Diagnosi di Epatite C Acuta (AHC):
Per infezione acuta da HCV si intende una sieroconversione documentata alla positività agli anticorpi anti-HCV nei 4 mesi precedenti lo screening, oppure una esposizione nota o sospetta al virus HCV nei 4 mesi precedenti lo screening, con un innalzamento dei valori di alanina aminotransferasi > 10 volte il limite superiore della norma allo screening oppure nelle 4 settimane precedenti lo screening.

E.4

Principal exclusion criteria

- Patients fulfilling the criteria for acute liver failure (evidence of coagulation abnormality, INR > 1.5, and any degree of encephalopathy) (6).
- HBV co-infection;
- Patients with previous HCV infection cured by DAA regimens who were reinfected after HCV clearance
- Patients with chronic liver disease of any other etiology (NASH, ASH, autoimmune, metabolic);
- Concomitant use with atazanavir and rifampicin;
- Hypersensitivity to the active substances or to any of the excipients;
- Pregnancy.

Sono Previsti i Seguenti Criteri di Esclusione:
- Pazienti che presentano i criteri che definiscono l’insufficienza epatica acuta (riscontri di alterazione del profilo di coagulazione, INR > 1,5, ed encefalopatia di qualsiasi grado) (6).
- Coinfezione con HBV;
- Pazienti con infezione da HCV pregressa trattata con regime DAA e che hanno presentato re- infezione successiva alla clearance del virus HCV
- Pazienti con epatopatia cronica di qualsiasi altra eziologia (NASH, ASH, autoimmune, metabolica);
- Uso concomitante di atazanavir e rifampicina;
- Ipersensibilità alle sostanze attive oppure a qualsiasi fra gli eccipienti;
- Gravidanza.

E.5 End points

E.5.1

Primary end point(s)

The protocol-defined primary endpoint was SVR, defined as s undetectable HCV RNA at 12 weeks after the end of treatment;
Patients who discontinued the study for any reason before the 12-weeks follow-up visit will be considered as drop-out.

L’endpoint primario stabilito dal protocollo è rappresentato dalla risposta SVR, definita come livelli non rilevabili di HCV RNA 12 settimane dopo la fine del trattamento;
I pazienti che interrompono la sperimentazione per qualsiasi motivo prima della visita di follow-up a 12 settimane saranno considerati come drop-out.

E.5.1.1

Timepoint(s) of evaluation of this end point

12° weeks after end of therapy

12° settima di follow up

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

2, 4, 5 weeks of therapy; 12 weeks of follow up

2, 4 e 6 settimane di terapia. 12° settimana di follow up

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

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)

Yes

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.8.2.4

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

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

Information not present in EudraCT

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

last visit last patient

ultima visita ultimo paziente

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

Yes

F.3.3.2

Women of child-bearing potential using contraception

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)

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

2018-11-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-03-04

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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