Clinical Trials Register

Summary
EudraCT Number:	2016-003414-26
Sponsor's Protocol Code Number:	ZEP-HEPC-001
National Competent Authority:	Ireland - HPRA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2017-09-06
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

Ireland - HPRA

A.2

EudraCT number

2016-003414-26

A.3

Full title of the trial

An open label study of the safety and efficacy of FDC Zepatier (elbasvir and grazoprevir +/- Ribavirin) administered in a community-based setting to HCV infected G1/4 treatment naïve patients on stable opiate substitution therapy with cirrhotic and non-cirrhotic liver disease

A.3.1

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

Evaluation of Zepatier in a community-based setting among hepatitis infected cirrhotic and non-cirrhotic patients on stable opiate substitution therapy.

A.3.2

Name or abbreviated title of the trial where available

The Dublin Zepatier Study

A.4.1

Sponsor's protocol code number

ZEP-HEPC-001

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02895958

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	Dr. John Lambert (Mater Misericordiae University Hospital)
B.1.3.4	Country	Ireland
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	MSD
B.4.2	Country	Ireland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Mater Misericordiae University Hospital
B.5.2	Functional name of contact point	Catherine McAuley Research Centre
B.5.3	Address:
B.5.3.1	Street Address	Nelson Street
B.5.3.2	Town/ city	Dublin
B.5.3.3	Post code	7
B.5.3.4	Country	Ireland
B.5.6	E-mail	jlambert@mater.ie

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 50mg/100mg film-coated tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp and Dohme
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
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.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	Rebetol
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	European Union
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	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
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.IMP: 3
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	Rebetol
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	European Union
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	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
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

HCV Genotypes 1/4

E.1.1.1

Medical condition in easily understood language

Hepatitis C Virus infected patients, with genotype 1a, 1b or 4

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

Primary objective of the study is to evaluate effectiveness of Zepatier(+/- ribavirin) among cirrhotic and non-cirrhotic patients on stable opiate substitution therapy who are followed in a community-based setting.

E.2.2

Secondary objectives of the trial

• to evaluate safety of Zepatier(+/- ribavirin)
• to evaluate tolerability of Zepatier(+/- ribavirin)
• to evaluate long-term risk of HCV relapse and/or HCV reinfection over a 24-week period
• to demonstrate a new model of community-based integrated care to best reach and treat vulnerable HCV populations
• to compare results of present study to results of previous studies (historical control)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subject is ≥18 years of age.
2. Subject must be HCV treatment naive. Subject is willing and able to understand and provide written informed consent prior to participation in this study.
3. Documented chronic HCV infection (RNA positive), HCV RNA levels > 10x4 IU/ml.
4. Documented HCV genotype 1 and 4.
5. Documented HIV and HBV uninfected (HIV Ab negative, HBsAg negative)
6. 6. A female is eligible to enter and participate in the study if she is of:
• non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal); or,
• Child-bearing potential, has a negative pregnancy test (serum β-HCG) at screen and agrees to two acceptable methods of contraception; a barrier method and one other method of contraception e.g. progesterone-only contraception associated with inhibition of ovulation: oral, injectable, implantable (intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion). Any contraception method must be used consistently and correctly, i.e., in accordance with both the approved product label and the instructions of a physician. Male subjects and their female partners must agree to 7 months post-treatment contraception if taking ribavirin. Female subjects must agree to 4 months post-treatment contraception if taking Ribavirin. Both male (and their female partners) and female subjects must agree to one month post-treatment contraception if taking Zepatier only. A male subject taking Ribavirin must agree to use condoms throughout the period of treatment whether or not their partner is pregnant.
7. Stable attender in the site of enrolment (receiving OST at least 3 months before enrolment and were at least 80 % adherent to OST appointments)
8. Venous access available for blood monitoring.
9. Fibroscan done as per HSE Hepatitis C Advisory Group guidelines.
10. Safety bloods done prior to study including a HGB > 9.5g/dL, platelets > 75,000, AST < 10x ULN, albumin levels > 30g/L, ALT < 10 times the ULN.

E.4

Principal exclusion criteria

1. Child Pugh B or C
2. HCV non-G1/G4
3. History of decompensated liver disease
4. Laboratory exclusions include platelet count <75,000, albumin <30gm/L, ALT >10 times ULN, AST > 10 x ULN, HGB < 9.5g/dL
5. Subject is enrolled in one or more investigational drug protocols, which may impact on assessment of HCV treatment with Zepatier (+/_ ribavirin).
6. Subject is, in the opinion of the investigator, unable to complete the study dosing period and protocol evaluations and assessments.
7. Patients with alcohol and drug use problems that in the view of investigator will compromise adherence to compliance with the study will be excluded.
8. Subject is either pregnant or breastfeeding.
9. Subject suffers from any serious medical condition (such as pancreatitis, diabetes, congestive heart failure, cardiomyopathy or other cardiac dysfunction), which in the opinion of the Investigator, would compromise the safety of the subject.
10. Subject has a pre-existing mental, physical, or substance abuse disorder that, in the opinion of the Investigator, may interfere with the subject’s ability to comply with the dosing schedule and protocol evaluations and assessments.
11. Subject has a history of inflammatory bowel disease or intestinal malignancy, intestinal ischemia, malabsorption, or other gastrointestinal dysfunction, which, in the opinion of the Investigator, may interfere with drug absorption or render the subject unable to take oral medication.
12. Subject has any acute laboratory abnormality at screening, which, in the opinion of the Investigator, would preclude the subject’s participation in the study of an investigational compound. If subjects are found to have an acute Grade 4 laboratory abnormality at screening, this test may be repeated once within the 45-day screening window. Any verified Grade 4 laboratory abnormality would exclude a subject from study participation.
13. Subject has received treatment with radiation therapy or cytotoxic chemotherapeutic agents within 28 days prior to Screening, or has an anticipated need for these agents within the study period.
14. Subjects who require treatment with any contraindicated medications, as outlined in the SmPC, within the time period (as specified by MMUH pharmacist) of commencement of investigational product or during treatment.
15. Subject has a history of allergy to any of the treatment products or any excipients therein.

E.5 End points

E.5.1

Primary end point(s)

Primary endpoint of the study is sustained viral response (SVR) against HCV at 12 weeks after completion of study treatment.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 12 post -treatment

E.5.2

Secondary end point(s)

1. Sustained viral response (SVR) against HCV at 24 weeks after completion of study treatment
2. Incidence of adverse events during course of treatment
3. Characteristics of adverse events.
4. Incidence of treatment discontinuation over course of treatment
5. Rates of premature discontinuation of drug for clinical or laboratory reasons
6. Evaluation of percentage relapse at 12 and 24 weeks post treatment
7. Percentage of re-infection as evaluated by repeat HCV RNA positivity at weeks 12 and 24 post treatment
8. Safety and feasibility of model of community based integrated care with community dispensation and supervision of DAA therapy to treat ‘hard-to -reach’ HCV infected patients
9. Change in Quality of Life questionnaire score (EQ-5D-5L) administered at baseline, 12 weeks and post treatment 24 weeks

E.5.2.1

Timepoint(s) of evaluation of this end point

1. 24 Weeks post-treatment
2. From screening at -8 weeks to week 24 post-treatment
3. From screening at -8 weeks to week 24 post-treatment
4. Week 0- 12/16 of treatment
5. Week 0- 12/16 of treatment
6. Weeks 12 and 24 post-treatment
7. Weeks 12 and 24 post-treatment
8. End of study
9. End of study

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)

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

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.8.3

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

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

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

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

Yes

F.3.3.7.1

Details of other specific vulnerable populations

Drug users on stable opiate substitution therapy

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)

None

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

2017-11-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-12-12

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2019-12-06

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