Clinical Trials Register

Summary
EudraCT Number:	2018-003640-23
Sponsor's Protocol Code Number:	IRRB/05/18
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:	2021-01-22
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

2018-003640-23

A.3

Full title of the trial

USE OF HEPATITIS C+ DONORS FOR SOLID ORGAN TRANSPLANTATION IN A GEOGRAPHICAL AREA WITH HCV+ ENDEMIC INFECTION AND WITH A LOW-RATE CADAVERIC ORGAN DONOR AVAILABILITY.
A PHASE II OPEN, MONOCENTRIC CLINICAL STUDY.

UTILIZZO DI DONATORI POSITIVI PER INFEZIONE DEL VIRUS DELL’EPATITE C PER IL TRAPIANTO DI ORGANI SOLIDI IN UN’AREA ENDEMICA PER EPATITE C CON BASSO TASSO DI DONAZIONI DA CADAVERE: STUDIO CLINICO MONOCENTRICO APERTO DI FASE II.

A.3.1

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

PHASE II CLINICAL STUDY ON THE USE OF HCV+ DONORS FOR SOLID ORGAN TRANSPLANTATION.

STUDIO CLINICO DI FASE II PER L'UTILIZZO DI DONATORI HCV+ A SCOPO DI TRAPIANTO.

A.3.2

Name or abbreviated title of the trial where available

DONORHEPAC

A.4.1

Sponsor's protocol code number

IRRB/05/18

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	ISTITUTO MEDITERRANEO PER I TRAPIANTI E TERAPIE AD ALTA SPECIALIZZAZIONE - ISMETT
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	ISTITUTO MEDITERRANEO PER I TRAPIANTI AD ALTA SPECIALIZZAZIONE - ISMETT
B.5.2	Functional name of contact point	FARMACIA
B.5.3	Address:
B.5.3.1	Street Address	VIA ERNESTO TRICOMI, 5
B.5.3.2	Town/ city	PALERMO
B.5.3.3	Post code	90100
B.5.3.4	Country	Italy
B.5.4	Telephone number	0912192613
B.5.5	Fax number	0912192369
B.5.6	E-mail	FVENUTI@ISMETT.EDU

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	EPCLUSA
D.2.1.1.2	Name of the Marketing Authorisation holder	Gilead Sciences International Ltd
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	EPCLUSA SOFOSBUVIR 400MG/VELPATASVIR 100MG
D.3.2	Product code	[1BV30D]
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.3.9.1	CAS number	1190307-88-0
D.3.9.2	Current sponsor code	GS-7977
D.3.9.4	EV Substance Code	AS3
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	400
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	1377049-84-7
D.3.9.2	Current sponsor code	GS-5816
D.3.9.4	EV Substance Code	AS2
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

USE OF POSITIVE DONORS FOR INFECTION OF THE HEPATITIS VIRUS FOR THE TRANSPLANTATION OF SOLID ORGANS IN AN ENDEMIC AREA FOR HEPATITIS C WITH LOW RATE OF DONATIONS FROM CADAVERS: OPEN PHASE II CLINICAL STUDY.

E.1.1.1

Medical condition in easily understood language

HCV- patient to whom an organ from a HCV+ donor is transplanted who will receive Epclusa.

Pazienti HCV- a cui venga trapiantato un organo da donatore HCV+ che verranno trattati con Epclusa.

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10024714
E.1.2	Term	Liver transplant
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10063837
E.1.2	Term	Reperfusion injury
E.1.2	System Organ Class	10047065 - Vascular disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	PT
E.1.2	Classification code	10058060
E.1.2	Term	Graft complication
E.1.2	System Organ Class	10022117 - Injury, poisoning and procedural complications

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Single-center, open, phase II prospective study designed to evaluate the non-inferiority of the efficacy of HCV antiviral treatment in HCV-negative patients receiving a solid organ transplant (liver, kidney, heart, lung and pancreas) from positive donors for Hepatitis C virus (DONORHCV +).

Studio prospettico monocentrico, aperto, di fase II, disegnato per valutare la non inferiorità dell’efficacia del trattamento antivirale per HCV in pazienti HCV negativi riceventi un trapianto di organo solido (fegato, rene, cuore, polmone e pancreas) da donatori positivi per il virus dell’Epatite C (DONORHCV+).

E.2.2

Secondary objectives of the trial

- average annual number of organs, from HCV + donors, used for solid organ transplantation (liver, kidney, heart, lung, pancreas);
- absence of HCV infection (HCV-RNA negativity) 24 weeks after the completetion of antiviral treatment;
- adverse events of the drug;
- 12-month survival of the transplanted organ;
- absence of HCV (HCV-RNA negative) infection 48 weeks after the end of the antiviral treatment cycle (SVR48);
- 1-year survival of the transplanted organ;
- 5-year survival of the transplanted organ.

- numero di organi medio annuo, provenienti da donatori HCV+, utilizzati per trapianto di organo solido (fegato, rene, cuore, polmone, pancreas);
- assenza di infezione da HCV (HCV-RNA negativo) a 24 settimane dopo la conclusione del ciclo del trattamento antivirale (SVR24);
- eventi avversi del farmaco;
- sopravvivenza a 12 mesi dell’organo trapiantato;
- assenza di infezione da HCV (HCV-RNA negativo) a 48 settimane dopo la conclusione del ciclo del trattamento antivirale (SVR48);
- sopravvivenza a 1 anno dell’organo trapiantato;
- sopravvivenza a 5 anni dell’organo trapiantato.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) male or female recipient over 18 years of age.
2) negative candidate for HCV candidate and inserted in waiting list for solid organ transplant at IRCCS / ISMETT.
3) Female recipients potentially able to undertake a pregnancy who have committed themselves to ensure an effective practice of birth control during the first 6 months of study.
4) recipient affected by a terminal stage disease or oncological pathology, suitable candidate and included in waiting list for organ transplantation at IRCCS / ISMETT.
5) a patient who understands the purpose and risks of the study, who has been fully informed and has given written informed consent.
6) a patient unable to write and / or read, but who is fully capable of understanding the oral information proposed by the researcher (or the appointed representative) and who has given oral informed consent written in written form by an independent third person .

1) ricevente di sesso maschile o femminile oltre i 18 anni di età.
2) ricevente negativo per HCV candidato ed inserito in lista d’attesa per il trapianto di organo solido presso IRCCS/ISMETT.
3) ricevente di sesso femminile potenzialmente in grado di intraprendere una gravidanza che si siano impegnate a garantire una pratica efficace di controllo delle nascite durante i primi 6 mesi di studio.
4) ricevente affetto da una malattia allo stadio terminale o patologia oncologica, candidato idoneo ed inserito in lista d’attesa per il trapianto di organo presso IRCCS/ISMETT.
5) paziente in grado di comprendere lo scopo e i rischi dello studio, che sia stato pienamente informato e che abbia dato consenso informato scritto.
6) paziente incapace di scrivere e / o leggere, ma che sia pienamente capace di comprendere l'informazione orale proposta dal ricercatore (o dal rappresentante nominato) e che abbia dato il consenso informato per via orale testimoniata in forma scritta da una persona terza indipendente.

E.4

Principal exclusion criteria

1) patients with acute organ failure
2) pediatric patients or pediatric donor solid organ transplant candidates
3) patient in poor multi-organ clinical conditions
4) patient candidate for multi-organ transplantation
5) participant or who has participated in another clinical trial and / or who is taking or has taken an experimental drug in the last 30 days
6) patient with absolute improbability to respect the programmatic visits foreseen by the protocol
7) patient with any form of substance abuse, and / or carrier of psychiatric disorders or a condition that, in the opinion of the investigator, can invalidate the communication with the researcher himself.
8) patient over the age of 70.

1) pazienti con insufficienza d’organo acuta
2) pazienti pediatrici o candidati a trapianto di organo solido da donatore pediatrico
3) paziente in scarse condizioni cliniche multi-organo
4) paziente candidato a trapianto multiorgano
5) paziente partecipante o che abbia partecipato a un altro studio clinico e / o che stia assumendo o che abbia assunto un farmaco sperimentale negli ultimi 30 giorni
6) paziente con assoluta improbabilità a rispettare le visite programmatiche previste dal protocollo
7) paziente con qualsiasi forma di abuso di sostanze, e / o portatore di disturbi psichiatrici o di una condizione che, a giudizio dello sperimentatore, possa invalidare la comunicazione con il ricercatore stesso.
8) paziente di età superiore ai 70 anni.

E.5 End points

E.5.1

Primary end point(s)

Absence of HCV infection (negative HCV-RNA) at 12-weeks after completation of the cycle of antiviral treatment.

Assenza di infezione da HCV (HCV-RNA negativo) 12 settimane dopo il completamento del ciclo del trattamento antivirale.

E.5.1.1

Timepoint(s) of evaluation of this end point

12 weeks after the 12-week antiviral treatment cycle has been discontinued.

12 settimane dopo la sospensione del ciclo di trattamento antivirale di 12 settimane .

E.5.2

Secondary end point(s)

average annual number of organs, from HCV + donors, used for solid organ transplantation (liver, kidney, heart, lung, pancreas);; absence of HCV infection (negative HCV-RNA) at 24 and 48 weeks after completion of the cycle of antiviral treatment; adverse events of the drug;; 12-month and 5 years survival of the transplanted organ.

numero di organi medio annuo, provenienti da donatori HCV+, utilizzati per trapianto di organo solido (fegato, rene, cuore, polmone, pancreas);; assenza di infezione da HCV (HCV-RNA negativo) 24 e 48 settimane dopo il completamento del ciclo del trattamento antivirale.; eventi avversi del farmaco; sopravvivenza a 12 mesi e 5 anni dell’organo trapiantato.

E.5.2.1

Timepoint(s) of evaluation of this end point

for the duration of the study; 24 and 48 weeks after the 12-week antiviral treatment cycle has been discontinued; For the duration of the study; 12 months and 5 years after transplantation

per tutta la durata dello studio; 24 e 48 settimane dopo la sospensione del ciclo di trattamento antivirale di 12 settimane; Per tutta la durata dello studio; 12 mesi e 5 anni dopo il trapianto

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

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

Yes

E.8.2.3.1

Comparator description

nulla perchè non è più controllato

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

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

Yes

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:

170

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

Yes

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

212

F.4.2

For a multinational trial

F.4.2.1

In the EEA

212

F.4.2.2

In the whole clinical trial

212

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)

PATIENTS WILL BE FOLLOWED ACCORDING TO NORMAL CLINICAL PRACTICE

I PAZIENTI VERRANNO SEGUITI SECONDO NORMALE PRATICA CLINICA

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

2019-05-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-01-06

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2022-12-23

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