Clinical Trials Register

Summary
EudraCT Number:	2016-001363-37
Sponsor's Protocol Code Number:	RBHP_2016_ABERGEL
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-06-16
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

France - ANSM

A.2

EudraCT number

2016-001363-37

A.3

Full title of the trial

A Phase 3, Global, Multicenter, Open-Label Study to Investigate the Efficacy of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve, HCV GT1b-Infected Patients, with non-severe fibrosis.

Étude ouverte, multicentrique, de phase 3 pour évaluer l’efficacité de l’association à dose fixe Elbasvir/Grazoprevir pendant 8 semaines, chez des patients naïfs de traitements antiviraux et présentant une infection chronique au virus de l’hépatite C de génotype 1b avec un taux de fibrose hépatique faible

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

MK2

A.4.1

Sponsor's protocol code number

RBHP_2016_ABERGEL

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	CHU de Clermont-Ferrand
B.1.3.4	Country	France
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	CHU de Clermont-Ferrand
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	CHU de Clermont-Ferrand
B.5.2	Functional name of contact point	Patrick LACARIN
B.5.3	Address:
B.5.3.1	Street Address	58 rue Montalembert
B.5.3.2	Town/ city	Clermont-Ferrand
B.5.3.3	Post code	63000
B.5.3.4	Country	France
B.5.4	Telephone number	04.73.751.195
B.5.5	Fax number	04.73.754.730
B.5.6	E-mail	placarin@chu-clermontferrand.fr

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	ZEPATIER
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme 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.3.4	Pharmaceutical form	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.3.9.3	Other descriptive name	ELBASVIR
D.3.9.4	EV Substance Code	SUB174125
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	GRAZOPREVIR
D.3.9.4	EV Substance Code	SUB174126
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

viral hepatitis C

Hépatite virale chronique C de génotype 1b/ Patients ayant une fibrose hépatique faible

E.1.1.1

Medical condition in easily understood language

viral hepatitis C

hépatite C

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

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 primary objectives of this study are as follows:
• To evaluate the efficacy of of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve, HCV GT1b-Infected Patients, with non- severe fibrosis as measured by the proportion of subjects with sustained viral response 12 weeks after cessation of treatment (SVR 12).
• To evaluate the safety and tolerability of EBV/GZR treatment

Evaluer l’efficacité de l’association à dose fixe d’Elbasvir/Grazoprevir pendant 8 semaines chez des patients hépatite C, naïfs de traitement, génotype 1b, sans fibrose sévère en fonction de la réponse virale soutenue 12 semaines après la fin du traitement (SVR12 ) ; Evaluer l’innocuité et la tolérance du traitement Elbasvir/Grazoprevir

E.2.2

Secondary objectives of the trial

The secondary objectives of this study are as follows:
• To determine the proportion of subjects who attain SVR at 4 and 24 weeks after cessation of treatment (SVR4 and SVR24)
• To evaluate the proportion of subjects with virologic failure
• To evaluate the kinetics of circulating HCV RNA during treatment and after cessation of treatment.
• To evaluate the emergence of viral resistance to EBV/GZR during treatment and after cessation of treatment

Déterminer la proportion de sujets avec une réponse virale 4 et 24 semaines après la fin du traitement (SVR4 et SVR24). Evaluer la proportion de sujets en échec de réponse virologique. Evaluer la cinétique de l’ARN circulant du virus de l’hépatite C pendant le traitement et le suivi post traitement. Evaluer l’émergence de résistances virales dues à l’association Elbasvir/Grazoprevir pendant le traitement et le suivi post traitement

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1 - Willing and able to provide written informed consent
2 - Male or female, age ≥ 18 years
3 - Body Mass Index (BMI) ≥ 18 kg/m2
4 - HCV RNA ≥ 104 IU/mL at Screening
5- Chronic HCV infection (≥ 6 months) documented by prior medical history or liver biopsy. Only patients infected by genotype 1b virus will be included.
6 - Treatment-naïve with no prior exposure to any IFN, RBV, or approved or experimental HCV-specific DAA
7 – Non severe fibrosis (F < 2) according to Metavir score if a biopsy was performed or elasticity measured by Fibroscan® lower than 9.5 kPa or Fibrotest lower than 0.59 or Fibrometre lower than 0.63 if Fibroscan® cannot be performed.

1 – signature du consentement libre et éclairé
2 – Adulte de plus de 18 ans
3 – Indice de masse corporelle ≥ 18 kg/m2
4 – Charge virale VHC ≥ 104 IU/mL au screening
5 - Hépatite chronique C détectée depuis plus de 6 mois, avec un génotype 1b
6 – Patient naïf de tout traitement anti-VHC
7 – Fibrose minime à modérée (F < 2) selon score Métavir soit par biopsie hépatique, ou Fibroscan® inférieur à 9.5 kPa ou Fibrotest® inférieur à 0.59 ou Fibrometre® inférieur à 0.63

E.4

Principal exclusion criteria

1 - Medical histaru with significant event
2- Significant abnormal lab results at screening
3 - Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson’s disease, alfa-1 antitrypsin deficiency, cholangitis)
4 - Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)
5 - Clinically-relevant alcohol or drug abuse within 12 months of Screening. A positive drug screen will exclude subjects unless it can be explained by a prescribed medication; the diagnosis and prescription must be approved by the investigator

1 - Historique médical avec évènements significatifs
2 - Résultats de laboratoire hors normes au screening
3 – Maladie chronique du foie hors hépatite C (ex : Hemochromatose, Maladie de Wilson, Déficit en alpha-1 antitripsine, cholangiome…)
4 – Coinfection par le virus de l’hépatite B (VHB) ou le HIV
5 – Consommation excessive d’alcool ou de drogue dans les 12 mois précédent le screening.
6 – Utilisation de médicaments contre-indiqués ou interdits
7 – Hypersensibilité ou allergie connue à un principe actif, un composant ou un excipient présent dans le traitement

E.5 End points

E.5.1

Primary end point(s)

Sustained virologic response

réponse virale soutenue (SVR) ≥ à 96 % à 12 semaines après l’arrêt du traitement par un dosage de l’ARN circulant du VHC

E.5.1.1

Timepoint(s) of evaluation of this end point

12 weeks after end of treatment

12 semaines après l’arrêt du traitement

E.5.2

Secondary end point(s)

• To determine the proportion of subjects who attain SVR at 4 and 24 weeks after cessation of treatment (SVR4 and SVR24)
• To evaluate the proportion of subjects with virologic failure

E.5.2.1

Timepoint(s) of evaluation of this end point

4 and 24 weeks after cessation of treatment

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

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)

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

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

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 of the last subject

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

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

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.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)

standard care

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

2016-11-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-05-02

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-11-10

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