Clinical Trials Register

Summary
EudraCT Number:	2015-004200-38
Sponsor's Protocol Code Number:	64294178HPC2001
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-09-30
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2015-004200-38

A.3

Full title of the trial

A Phase 2b, Multicenter, Randomized, Open-label Study to Investigate the Efficacy, Safety and Pharmacokinetics of Different Treatment Regimens of AL-335, Odalasvir, and Simeprevir in Treatment-naïve and Treatment-experienced Subjects With Chronic Hepatitis C Virus Genotype 1, 2, 4, 5, and 6 Infection, without Cirrhosis.

A.3.1

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

A Phase 2 study of Different Treatment Combinations of AL-335, odalasvir and simeprevir in subjects with chronic hepatitis C virus infection

A.4.1

Sponsor's protocol code number

64294178HPC2001

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	Janssen-Cilag International NV
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	Janssen R&D LLC
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Janssen-Cilag International NV (Janssen Biologics)
B.5.2	Functional name of contact point	Clinical Registry Group
B.5.3	Address:
B.5.3.1	Street Address	Archimedesweg 29
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	2333 CM
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+3171524-2166
B.5.5	Fax number	+3171524-2110
B.5.6	E-mail	ClinicalTrialsEU@its.jnj.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	JNJ-38733214-AAA (G034)
D.3.2	Product code	SMV
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	simeprevir
D.3.9.1	CAS number	923604-59-5
D.3.9.2	Current sponsor code	SMV
D.3.9.3	Other descriptive name	JNJ-38733214-AAA (G034)
D.3.9.4	EV Substance Code	SUB64783
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	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	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	Odalasvir
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	ODALASVIR DIHYDRATE
D.3.9.3	Other descriptive name	JNJ-64289901-ZAT
D.3.9.4	EV Substance Code	SUB181206
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	25
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	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	JNJ-64146212
D.3.2	Product code	AL-335
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	n/a
D.3.9.2	Current sponsor code	JNJ-64146212-AAA
D.3.9.3	Other descriptive name	AL-335
D.3.9.4	EV Substance Code	SUB181205
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.3.11 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

Chronic Hepatitis C virus infection.

E.1.1.1

Medical condition in easily understood language

Chronic Hepatitis 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	19.0
E.1.2	Level	PT
E.1.2	Classification code	10019744
E.1.2	Term	Hepatitis C
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

• evaluate efficacy, ie, sustained virologic response 12 weeks after the end of treatment (SVR12), of a combination treatment with AL-335, ODV, and SMV for 6 and 8 weeks in chronic HCV genotype 1, 2, 4, 5 or 6 infected subjects without cirrhosis,

E.2.2

Secondary objectives of the trial

• evaluate safety and tolerability, SVR4 and SVR24, on-treatment viral
kinetics, of a 6- and 8-week treatment regimen containing AL-335, ODV,
and SMV in subjects without cirrhosis
• evaluate incidence of on-treatment failure during treatment
• evaluate incidence of viral relapse after treatment
• assess changes from baseline in HCV NS3/4A, NS5A, and NS5B
sequence in subjects not achieving SVR,
• evaluate effect of the presence or absence of baseline HCV NS3/4A
polymorphisms (including Q80K), NS5A polymorphisms and/or NS5B
polymorphisms on treatment outcome
• evaluate concordance between SVR4, SVR12, and SVR24,
• evaluate PK of AL-335, ODV, SMV, and their metabolites in plasma,
• evaluate relationship between population-derived exposure
parameters of AL-335, ODV, and SMV with SVR12 and safety,
• explore impact of HCV and treatment with AL-335+ODV+SMV on the
Fatigue Severity Scale total score and 5-level EuroQol 5-Dimension
Visual Analog Scale score.

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

• exploratory host DNA research related to SMV, ODV, AL-335 (and metabolites), or HCV infection.
• rich serial PK substudy, performed at selected study sites, rich serial PK blood sampling for the measurement of plasma concentrations of AL-335 (and its metabolites ALS-022227 and ALS-022399), SMV, and ODV will be performed in 20 subjects.
• sparse PK substudy, performed at selected sites, sparse PK sampling for AL-335 (and metabolites), SMV, and ODV will be performed for a subset of approximately 20 subjects who are not participating in the rich serial PK substudy.

E.3

Principal inclusion criteria

• Documented chronic HCV infection: diagnosis of HCV infection >6 months before the first screening assessment, either by detectable HCV RNA, an HCV positive antibody test or presence of histological changes
consistent with chronic hepatitis in a liver biopsy
• All subjects must have HCV genotype 1, 2, 4, 5 or 6 infection,
determined at screening
• HCV RNA plasma levels >10,000 IU/mL
• HCV treatment-naïve

E.4

Principal exclusion criteria

• Co-infection with multiple HCV genotypes
• Co-infection with HIV
• Presence of cirrhosis
• Prior exposure to an HCV DAA, either in combination with PegIFN or
IFN-free
• Any evidence of liver disease of non-HCV etiology
• Evidence of hepatic decompensation (history or current clinical
evidence of ascites, bleeding varices or hepatic encephalopathy)
• Subjects with HCV genotype 3 infection.

E.5 End points

E.5.1

Primary end point(s)

Percentage of Chronic HCV Infected Subjects who Achieve Sustained Virologic Response 12 weeks After the end of Treatment (EOT) (SVR12)

E.5.1.1

Timepoint(s) of evaluation of this end point

12 weeks after the EOT (Week 6 or 8)

E.5.2

Secondary end point(s)

• Percentage of Subjects with Sustained Virologic Response at 4 (SVR4)
and 24 (SVR24) Weeks After EOT
• Percentage of Subjects With Viral Relapse During Follow-up up to 24
Weeks After EOT
• Percentage of Subjects With On-treatment Failure
• Percentage of Subjects With Virologic Response
• Time to Achieve Undetectable HCV RNA <LLOQ HCV RNA
• Effect of Presence or Absence of Baseline NS5A, NS5B or NS3/4A
Genes Polymorphisms on Treatment Outcome
• Changes from Baseline in Amino Acid Sequence in the HCV NS3/4A,
NS5A and NS5B Genes in Subjects, who did not Achieve SVR
• Change from Baseline Over Time in 5-level EuroQol 5 Dimension
(EQ5D5L) Visual Analog Scale (VAS) Score
• Change from Baseline Over Time in Fatigue Severity Scale (FSS) Total
Score
• Percentage of Subjects with Clinically Significant Positive or Negative
Change from Baseline in FSS Total and EQ5D5L VAS at Week 4, EOT
(Week 6 or 8), Follow up Week 4, 12 and 24
• Duration of Clinically Significant Positive or Negative Response from
Baseline in FSS Total and EQ5D5L VAS at Week 4, EOT (Week 6 or 8),
Follow up Week 4, 12 and 24
• Predose (trough) Plasma Concentration (C0h)
• Area Under the Curve From Time Zero to 24 Hours Postdose (AUC 24)
• Number of Subjects with Adverse Events (AEs)

E.5.2.1

Timepoint(s) of evaluation of this end point

Each secondary end point respectively:
• 4 and 24 weeks after EOT
• Up to Week 24 of follow-up
• Up to 6 or 8 weeks depending upon the Treatment received
• Up to 6 or 8 weeks
• Up to 24 weeks of follow-up
• Baseline
• Baseline up to 24 weeks of follow-up
• Baseline up to 24 weeks of follow-up
• Baseline up to 24 weeks of follow-up
• Week 4, EOT, follow up Week 4, 12 and 24
• Week 4, EOT, follow up Week 4, 12 and 24
• Baseline (Day 1) up to EOT
• Baseline (Day 1) up to EOT
• Screening (Day 1) up to Week 38 (= Week 24 of 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

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

E.6.11

Pharmacogenomic

Yes

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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

historical data

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

Yes

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

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

Belgium

Canada

France

Germany

Italy

Poland

Singapore

Spain

Sweden

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:

285

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

201

F.4.2.2

In the whole clinical trial

300

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)

For subjects who do not achieve SVR and where possible, subjects may be allowed to enroll in a subsequent clinical study (re-treatment with the same 3-DAA regimen + RBV for 12 weeks) if he/she meets the relevant entry criteria. If not possible, the sponsor will reimburse treatment with the standard of care in the respective country.

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

2016-10-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-01-05

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-11-16

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