Clinical Trials Register

Summary
EudraCT Number:	2016-003607-59
Sponsor's Protocol Code Number:	HCV_AMH_16
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-06-08
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2016-003607-59

A.3

Full title of the trial

An Open-Label Study to Evaluate Long-Term Results With Ombitasvir-Paritaprevir-Ritonavir and Dasabuvir With or Without Ribavirin (RBV) on ovarian function in fertile women With Genotype 1 and 4 Chronic Hepatitis C Virus (HCV) Infection.

Studio in aperto per valutare i risultati a lungo termine con Ombitasvir-paritaprevir-Ritonavir e Dasabuvir, con o senza ribavirina (RBV) sulla funzione ovarica delle donne in et¿ fertile con epatite cronica HCV-positiva, genotipo 1 e 4 .

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

HCV_AMH_16

A.4.1

Sponsor's protocol code number

HCV_AMH_16

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02950870

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	DIPARTIMENTO AD ATTIVITà INTEGRATA CHIRURGICO, MEDICO, ODONTOIATRICO E DI SCIENZE MORFOLOGICHE
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 SRL
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	DIPARTIMENTO AD ATTIVIT¿ INTEGRATA CHIRURGICO, MEDICO, ODONTOIATRICO E DI SCIENZE MORFOLOGICHE
B.5.2	Functional name of contact point	UO GASTROENTEROLOGIA
B.5.3	Address:
B.5.3.1	Street Address	VIA DEL POZZO 71
B.5.3.2	Town/ city	MODENA
B.5.3.3	Post code	41124
B.5.3.4	Country	Italy
B.5.4	Telephone number	0594224359
B.5.5	Fax number	0594224424
B.5.6	E-mail	villa.erica@unimore.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	VIEKIRAX - 12,5MG/75MG/50MG COMPRESSA RIVESTITA CON FILM - USO ORALE - BLISTER (PVC/PE/PCTFE/ALU) - 56 COMPRESSE (CONFEZIONE MULTIPLA)
D.2.1.1.2	Name of the Marketing Authorisation holder	ABBVIE LTD
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	VIEKIRAX
D.3.2	Product code	043841
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	OMBITASVIR
D.3.9.2	Current sponsor code	OMBITASVIR
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	12
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PARITAPREVIR
D.3.9.2	Current sponsor code	PARITAPREVIR
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	75
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	RITONAVIR
D.3.9.2	Current sponsor code	RITONAVIR
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.3.11 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.IMP: 2
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	EXVIERA - 250 MG COMPRESSA RIVESTITA CON FILM - USO ORALE - BLISTER (PVC/PE/PCTFE/ALU) - 56 COMPRESSE (CONFEZIONE MULTIPLA)
D.2.1.1.2	Name of the Marketing Authorisation holder	ABBVIE LTD
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	EXVIERA
D.3.2	Product code	043840
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	DASABUVIR
D.3.9.2	Current sponsor code	DASABUVIR
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	250
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

Genotype 1 and 4 Chronic Hepatitis C Virus (HCV) Infection

Epatite cronica HCV-positiva, genotipo 1 e 4

E.1.1.1

Medical condition in easily understood language

Hepatitis C

EPATITE C

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

The modification of AMH levels before and after successful antiviral therapy in comparison with age-matched HCV-positive women not undergoing antiviral treatment is the primary endpoint

Valutare i livelli di AMH nelle donne sottoposte a terapia antivirale e paragonarli a quelli delle donne di pari et¿ HCV positive non sottoposte a terapia

E.2.2

Secondary objectives of the trial

1. Modification of AMH levels before and after successful antiviral therapy
2. Modification of the Estradiol (E2) levels
3. Percentage of participants experiencing miscarriage during 3 years observation post-therapy.

1. Valutazione a lungo termine dei livelli di AMH in donne sottoposte a terapia antivirale
2. Modificazione dei livelli di estradiolo.
3. Valutazione della percentuale di partecipanti che registrano un evento di aborto spontaneo nei 3 anni successi alla terapia.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Childbearing potential and sexually active with male partner(s) currently using at least one effective method of birth control at the time of screening and two effective methods of birth control while receiving study drugs, starting with Study Day 1 and for 7 months after stopping study drug.
- Negative serum test within 24 hours prior to the start of investigational product.
- Chronic HCV-infection prior to study enrollment
- Screening laboratory result indicating HCV GT 1b or GT 1a or GT 4 infection.
- Liver biopsy within 24 months prior to or during screening demonstrating a Metavir score of 2 or less or an Ishak score of 3 or less or Screening FibroScan® result of = 9.6 kPa;
- Must be able to voluntarily sign and date an informed consent form.

- Risultato negativo a test di gravidanza su siero 24 ore prima la somministrazione del farmaco.
- Donne affette da HCV virus
- Test di laboratorio indicativi di HCV Genotipo 1 a, 1 b o 4
- Biopsia epatica eseguita nei 24 mesi precedenti o durante lo screening che dimostri un punteggio Metavir uguale o inferiore a 2 o un punteggio Ishak inferiore o uguale a 3 o allo screening un Fibroscan® = a 9,6 kPa;
-Donne fertili e sessualmente attive con partner di sesso maschile che utilizzano dal momento dello screening un efficace metodo anticoncezionale e accettano di utilizzarne due efficaci durante il periodo di trattamento, a partire dal primo giorno dello studio fino a 7 mesi dalla sospensione della terapia.
- Donne che praticano astinenza sessuale o che non sono eterosessualmente attive.
- Firma del consenso informato

E.4

Principal exclusion criteria

- Women who are pregnant or breastfeeding
- Hypersensitivity to the active substance or to any of the excipients
-Positive test result for HBsAg and HIV Ab
-Recent history of drug or alcohol
-History pf severe pre- existing cardiac disease, including unstable or uncontrolled cardiac disease in the previous six month
- Presence of haemoglobinopathies
- HCV genotype performed during screening indicates more than 1 subtype or co-infection with any other genotype.
-Use of medications contraindicated
-Use of known strong inducers of cytochrome P450 3A (CYP3A) or strong inducers of cytochrome P450 2C8 (CYP2C8) or strong inhibitors of CYP2C8
-History of solid organ transplant.
-Confirmed presence of hepatocellular carcinoma
-Current use of any investigational or commercially available anti-HCV agents
-Screening laboratory analyses showing any of the following abnormal laboratory results

- Gravidanza o allattamento.
- Ipersesibilità al princio attivo o agli eccipienti
- HBsAg positività o HIV anticorpi positività.
- Pregresso utilizzo di droghe o alcol
- Malattie cardiache severe pre-esistenti o negli ultimi 6 mesi.
- Presenza di emoglobinopatie
- Presenza di coesistenza di diversi sottotipi o genotipi HCV.
- Utilizzo di farmaci controindicati per Ombitasvir-Paritaprevir-Ritonavir e Dasabuvir, o per RBV
- Utilizzo di forti induttori del citocromo P450 3A (CYP3A) o del citocromo P450 2C8 (CYP2C8) o di forti inibitori del CYP2C8
- Trapianto di organo solido.
- Diagnosi di carcinoma epatocellulare
- Precedente terapia con antivirali ad azione diretta (DAA)
- Presenza di insufficienza epatica (Child - Pugh Class B or C)
- Valori di laboratorio alterati.

E.5 End points

E.5.1

Primary end point(s)

Evaluation of the modification of AMH levels after successful antiviral therapy, during 48 weeks post treatment.

Valutare le variazioni dei livelli di AMH nelle pazienti trattate.

E.5.1.1

Timepoint(s) of evaluation of this end point

48 weeks post treatment

Da valutare nelle 48 settimane post-trattamento

E.5.2

Secondary end point(s)

Evaluation of the AMH and estradiolo levels after successful antiviral therapy.

Valutare le variazioni dei livelli di AMH e di ormone estradiolo nelle pazienti trattate.

E.5.2.1

Timepoint(s) of evaluation of this end point

84 weeks of follow up.

84 settimane 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

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

Yes

E.7.1.3.1

Other trial type description

STUDY OF EFFICACY

STUDIO DI EFFICACIA

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

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

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.8.5.1

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

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

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)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

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

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)

Patients at the end of the study will still be followed according to clinical practice

I pazienti al termine della partecipazione allo studio verranno comunque seguite secondo 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

2017-03-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-12-13

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials