Clinical Trials Register

Summary
EudraCT Number:	2013-002458-66
Sponsor's Protocol Code Number:	AI443-113
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:	2015-06-19
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

France - ANSM

A.2

EudraCT number

2013-002458-66

A.3

Full title of the trial

A Phase 3 Evaluation of a daclatasvir/asunaprevir/BMS-791325 Fixed Dose Combination in Subjects with Genotype 1 Chronic Hepatitis C and Compensated Cirrhosis

A.3.1

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

A Study of an investigational treatment regimen of daclatasvir (DCV) + asunaprevir (ASV) + BMS-791325 in a fixed dose combination (the triple regimen) with or without ribavirin (RBV) for 12 weeks for the treatment of chronic hepatitis C virus (HCV) genotype 1 infection in subjects with compensated cirrhosis

A.4.1

Sponsor's protocol code number

AI443-113

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	Bristol-Myers Squibb International Corporation
B.1.3.4	Country	Belgium
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Bristol-Myers Squibb International Corporation
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Bristol-Myers Squibb International Corporation
B.5.2	Functional name of contact point	EU Study Start-Up Unit
B.5.3	Address:
B.5.3.1	Street Address	Parc de l'Alliance - Avenue de Finlande, 4
B.5.3.2	Town/ city	Braine-l'Alleud
B.5.3.3	Post code	1420
B.5.3.4	Country	Belgium
B.5.6	E-mail	clinical.trials@bms.com

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	No
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	BMS-790052/BMS-650032/BMS-791325 Fixed-dose combination
D.3.2	Product code	FDC
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	Daclatasvir
D.3.9.1	CAS number	1009119-64-5
D.3.9.2	Current sponsor code	BMS-790052/DCV
D.3.9.3	Other descriptive name	DACLATASVIR
D.3.9.4	EV Substance Code	SUB34092
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	30
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Asunaprevir
D.3.9.1	CAS number	630420-16-5
D.3.9.2	Current sponsor code	BMS-650032/ASV
D.3.9.3	Other descriptive name	ASUNAPREVIR
D.3.9.4	EV Substance Code	SUB34091
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	200
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	N/A
D.3.9.1	CAS number	958002-36-3
D.3.9.2	Current sponsor code	BMS-791325
D.3.9.3	Other descriptive name	HCV NS5B POLYMERASE INHIBITOR
D.3.9.4	EV Substance Code	SUB32943
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.3.11 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	Yes
D.3.11.13.1	Other medicinal product type	Fixed-dose combination
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Ribasphere
D.2.1.1.2	Name of the Marketing Authorisation holder	Kadmon Pharmaceuticals, LLC
D.2.1.2	Country which granted the Marketing Authorisation	United States
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	RIBAVIRIN
D.3.9.1	CAS number	36791-04-5
D.3.9.3	Other descriptive name	RIBAVIRIN
D.3.9.4	EV Substance Code	SUB10297MIG
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	200
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

HEPATITIS C VIRUS

E.1.1.1

Medical condition in easily understood language

HEPATITIS C VIRUS

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	18.0
E.1.2	Level	LLT
E.1.2	Classification code	10072848
E.1.2	Term	Hepatitis C virus genotype 1 positive
E.1.2	System Organ Class	100000004848

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To demonstrate the effectiveness of Triple fixed dose combination with or without ribavirin in treatment naive cirrhotic subjects

E.2.2

Secondary objectives of the trial

Only key secondary objectives are listed, for others please refer to the protocol
- Proportion of treated subjects in each of the experienced arms with SVR12, defined as HCV RNA < LOQ target detected or target not detected (LOQ TD/TND) at post treatment Week 12.
- Proportion of subjects in each arm who achieve HCV RNA < LOQ TD/TND at each of the following Weeks: 1, 2, 4, 6, 8, and 12; post treatment Weeks 4 , 8 and 24 ;
- Proportion of subjects in each arm who achieve HCV RNA < LOQ TND at each of the following Weeks: 1, 2, 4, 6, 8, and 12; post treatment weeks 4, 8, 12 and 24;
- On treatment safety, as measured by frequency of SAEs and discontinuations due to AEs through the end of treatment in each arm within each cohort

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Pharmacogenetics Blood Sample Amendment 01, version 2.0, dated 11-Oct-2013

The objective of this Amendment is to permit the collection and storage of blood samples for use in future exploratory pharmacogenetic research. Bristol-Myers Squibb will use DNA obtained from the blood sample and health information collected from the main clinical trial, AI443113 to study the association between genetic variation and drug response. Bristol-Myers Squibb may also use the DNA to study the causes and further progression of Hepatitis C. Samples from this
study may also be used in conjunction with pharmacogenetic research results from other clinical studies to accomplish this objective.

E.3

Principal inclusion criteria

Key Inclusion Criteria:
• Subjects chronically infected with HCV genotype 1
• Subjects with compensated cirrhosis;
• HCV RNA ≥ 10,000 IU/mL at screening;
• Treatment-naïve subjects with no previous exposure to an interferon formulation (ie, IFNα, pegIFNα), RBV, or HCV DAA (protease, polymerase inhibitor, etc.)
• Treatment-experienced subjects are eligible including exposure to anti-HCV agents of a mechanistic class other than those contained in the DCV/ASV/BMS-791325 triple regimen is permitted. Examples of permitted agents include, but are not limited to nucleoside/nucleotide inhibitors of NS5B polymerase, inhibitors of cyclophilin, or inhibitors of
microRNA.

E.4

Principal exclusion criteria

Key Exclusion Criteria:
• Subjects without cirrhosis
• Liver or any other organ transplant
• Current or known history of cancer within 5 years prior to screening;
• Documented or suspected HCC,;
• Evidence of decompensated liver disease including, but not limited to, radiologic criteria, a history or presence of ascites, bleeding varices, or hepatic encephalopathy

E.5 End points

E.5.1

Primary end point(s)

Proportion of treated subjects in each of the naive arms with SVR12, defined as HCV RNA < LOQ target detected or target not detected (LOQ TD/TND) at post treatment Week 12.

E.5.1.1

Timepoint(s) of evaluation of this end point

Post-Treatment Week 12

E.5.2

Secondary end point(s)

- Proportion of treated subjects in each of the experienced arms with SVR12, defined as HCV RNA < LOQ target detected or target not detected (LOQ TD/TND) at post treatment Week 12.
- Proportion of subjects in each arm who achieve HCV RNA < LOQ TD/TND at each of the following Weeks: 1, 2, 4, 6, 8, and 12; post treatment Weeks 4 , 8 and 24 ;
- Proportion of subjects in each arm who achieve HCV RNA < LOQ TND at each of the following Weeks: 1, 2, 4, 6, 8, and 12; post treatment weeks 4, 8, 12 and 24;
- On treatment safety, as measured by frequency of SAEs and discontinuations due to AEs through the end of treatment in each arm within each cohort;
- Proportion of subjects with anemia defined as Hg < 10 g/dL on-treatment in each arm within each cohort;
- Differences in rates of selected Grade 3 - 4 laboratory test result abnormalities (hematologic and liver function) between arms within each cohort;
- Proportion of subjects achieving SVR12 associated with HCV geno subtype 1a vs 1b within each arm of each cohort;
- Proportion of subjects in each arm achieving SVR12 associated with IL28B rs12979860 SNP status (CC genotype or non-CC genotype).

E.5.2.1

Timepoint(s) of evaluation of this end point

- Post treatment Week 12.
- On-treatment Weeks: 1, 2, 4, 6, 8, and 12; post treatment Weeks 4 (SVR4), 8 (SVR8) and 24 (SVR24);
- Weeks: 1, 2, 4, 6, 8, and 12 and post treatment weeks 4, 8, 12 and 24;
- On treatment
- On treatment
- On treatment
- Post treatment Week 12
- Post treatment Week 12

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

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Biomarker Assessments, Virologic Resistance Testing, Brief Questionnaire/Interim Phone Contacts

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

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

Triple FDC is used with or without Ribavirin (and Ribavirin placebo used to maintain the blind)

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Canada

France

United States

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

The end of the study will be considered the last subject’s last visit date, or the date the last data point required for statistical analysis is received from 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

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:

282

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.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

425

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)

At the end of the study, BMS will not continue to supply study drug to subjects/investigators unless BMS chooses to extend the study. The investigator should ensure that the subject receives appropriate standard of care to treat the condition under study.
No rescue therapy is offered in this study and post-study drug program is not anticipated for any molecule within the HCV program.

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

2013-12-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-12-06

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-11-26

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