Clinical Trials Register

Summary
EudraCT Number:	2017-001647-12
Sponsor's Protocol Code Number:	ARB-001467-003
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2017-10-24
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

Spain - AEMPS

A.2

EudraCT number

2017-001647-12

A.3

Full title of the trial

A Phase 2a, Open-Label, Study Evaluating the Safety and Anti-Viral Activity of ARB-001467 in Non-Cirrhotic, HBeAg-Negative Subjects with Chronic HBV Infection (Genotype A or B) in Combination with PEG-IFN α-2a and Tenofovir Disoproxil Fumarate

Estudio de fase IIa abierto para evaluar la seguridad y la actividad antiviral de ARB-001467 en combinación con peginterferón α2a y tenofovir disoproxil fumarato, en pacientes con infección crónica por el virus de la hepatitis B (genotipo A o B) HBeAg-negativo sin cirrosis

A.3.1

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

A study to determine how safe the treatment is for subjects diagnosed with hepatitis B virus infections when combined with other treatments for hepatitis B. Subjects must have no evidence of liver damage.

Un estudio para determinar la seguridad del tratamiento para los sujetos diagnosticados con infecciones por el virus de la hepatitis B cuando se combinan con otros tratamientos para la hepatitis B.
Los sujetos no deben tener evidencia de daño hepático.

A.4.1

Sponsor's protocol code number

ARB-001467-003

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1197-0708

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	Arbutus Biopharma Corporation
B.1.3.4	Country	Canada
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	Arbutus Bipoharma Corporation
B.4.2	Country	Canada
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Arbutus Biopharma Corporation
B.5.2	Functional name of contact point	Arbutus Regulatory Affairs
B.5.3	Address:
B.5.3.1	Street Address	100-8900 Glenlyon Parkway
B.5.3.2	Town/ city	Burnaby, BC
B.5.3.3	Post code	V5J-5J8
B.5.3.4	Country	Canada
B.5.4	Telephone number	1267422-2652
B.5.5	Fax number	1604430-8347
B.5.6	E-mail	regulatory@arbutusbio.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	ARB-001467
D.3.2	Product code	ARB-001467
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not assigned
D.3.9.1	CAS number	Not assigned
D.3.9.2	Current sponsor code	UsiHBV-1
D.3.9.3	Other descriptive name	T05M
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
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	Viread
D.2.1.1.2	Name of the Marketing Authorisation holder	Gilead Sciences International Limited
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.3.1	Product name	Viread
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: 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	Pegasys
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Products, 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.3.1	Product name	Pegasys
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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

Hepatitis B virus e-antigen (HBeAg)-negative subjects with chronic hepatitis B virus infection (CHB)

Pacientes con infección crónica por el virus de la hepatitis B (HBC) HBeAg-negativo sin cirrosis

E.1.1.1

Medical condition in easily understood language

Subjects infected with hepatitis B virus

Los sujetos infectados con el virus de la hepatitis B

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	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10054283
E.1.2	Term	HBV DNA detectable
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 explore the anti-viral efficacy of combination therapy with ARB-001467 plus TDF and PEG-IFN α-2a in subjects with chronic hepatitis B (CHB) due to HBV genotype A or B, who are HBV-DNA positive

Explorar la eficacia antiviral del tratamiento combinado con ARB-001467 más TDF y PEG-IFN α2a, en pacientes con hepatitis B crónica (HBC) por el virus del genotipo A o B que presentan ADN del VHB.

E.2.2

Secondary objectives of the trial

To evaluate the proportion of subjects who achieve HBsAg <lower limit of quantification (LLOQ) and who achieve HBV-DNA <LLOQ throughout the study

To evaluate on-treatment safety as measured by the frequency of adverse events (AEs), discontinuations due to AEs, and selected Grade 3-4 laboratory abnormalities (based on the Common Terminology Criteria for Adverse Events [CTCAE] criteria) 

Evaluar la proporción de pacientes que logran una concentración de HBsAg por debajo del límite inferior de cuantificación (LIC) y de ADN del VHB inferior al LIC a lo largo del estudio.

Evaluar la seguridad durante el tratamiento, determinada a través de la frecuencia de acontecimientos adversos (AA), las interrupciones del tratamiento debidas a AA y la incidencia de anomalías analíticas seleccionadas de grados 3-4 (sobre la base de los Criterios terminológicos comunes para acontecimientos adversos [Common Terminology Criteria for Adverse Events, CTCAE]).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Chronic HBV infection as documented at screening by either:
a. Positive HBsAg, or hepatitis B virus e-antigen (HBeAg; negative or positive) or HBV-DNA at least 6 months prior to screening; OR
b. Historical liver biopsy consistent with chronic HBV infection with documentation available at screening
2. Subject must be HBV-DNA(+) with a HBV-DNA ≥1000 IU/mL and either treatment-naive or treatment-experienced, defined as follows:
a. Treatment naïve subjects: Subjects have never received nucleos(t)ide analogue (NA) therapies including, but not limited to, TDF, entecavir, telbivudine, or lamivudine and/or interferon-alpha; OR
b. Treatment experienced subjects: Subjects may have previously had NA therapies (including, but not limited to, TDF, entecavir, telbivudine, or lamivudine) and/or interferon-alpha therapy, but must have discontinued treatment at least 6 months prior to screening
3. Quantitative HBsAg ≥1000 IU/mL at the Screening Visit
4. HBV genotype A or B at the screening visit
5. Interleukin (IL)28B CC Genotype
6. HBeAg-negative at the screening visit

1. Infección crónica por el VHB documentada en la selección de la siguiente manera:
a. HBsAg positivo, antígeno e del virus de la hepatitis B (HBeAg; negativo o positivo) o detección de ADN del VHB al menos 6 meses antes de la selección; b. biopsia hepática previa indicativa de infección crónica por el VHB con documentación disponible en la selección.
2. Presencia de ADN del VHB, con valores ≥1000 UI/ml y pacientes con o sin tratamiento previo, definidos de la siguiente manera:
a.Pacientes sin tratamiento previo: nunca han recibido tratamiento con análogos de nucleótidos o de nucleósidos (AN) como TDF, entecavir, telbivudina o lamivudina, ni con interferón α; O
b.Pacientes con tratamiento previo: pueden haber recibido anteriormente tratamiento con AN (entre otros, TDF, entecavir, telbivudina o lamivudina) o con interferón α, sin embargo, deben haber dejado de recibirlo al menos 6 meses antes de la selección.
3. HBsAg cuantitativo ≥1000 UI/ml en la visita de selección.
4. VHB de genotipo A o B en la visita de selección.
5. Interleucina (IL) 28B CC Genotipo
6. HBeAg negativo en la visita de selección.

E.4

Principal exclusion criteria

1. Known co infection with any of the following: Human immunodeficiency virus (HIV), Hepatitis C virus (HCV), Hepatitis D virus (HDV), or Hepatitis E virus (HEV).
2. Any known pre existing medical or psychiatric condition that could interfere with the subject’s ability to provide informed consent or participate in study conduct, or that may confound study findings.

1. Infección concomitante conocida con alguno de los siguientes: virus de la inmunodeficiencia humana (VIH), virus de la hepatitis C (VHC), virus de la hepatitis D (VHD), o virus de la hepatitis E (VHE).
2. Alguna enfermedad física o mental preexistente conocida que pudiera interferir en la capacidad del paciente para otorgar el consentimiento informado o participar en el estudio, o que pueda confundir los resultados de este.

E.5 End points

E.5.1

Primary end point(s)

Proportion of treated subjects with HBsAg decline ≥2 log10

Proporción de pacientes tratados que presenten una disminución del HBsAg ≥2 log10

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 30

Semana 30

E.5.2

Secondary end point(s)

1) Proportion of subjects who achieve HBsAg <LLOQ and who achieve HBV-DNA <LLOQ
2)On-treatment safety as measured by frequency of AEs, discontinuations due to AEs, and selected Grade 3-4 laboratory abnormalities (including hematologic and liver function, based on CTCAE criteria)

1) Proporción de pacientes con HBsAg < LIC y ADN del VHB < LIC
2) Seguridad durante el tratamiento, determinada a través de la frecuencia de AA, las interrupciones del tratamiento debidas a AA y la incidencia de anomalías analíticas seleccionadas de grados 3-4 (como las hematológicas y las funcionales hepáticas, sobre la base de los CTCAE).

E.5.2.1

Timepoint(s) of evaluation of this end point

1) Weeks: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28 and 30; and Post-treatment Weeks 4, 8, 12 and 24
2) Throughout course of study treatment up to 28 days after the last dose of study treatment.

1) Semanas: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28 y 30; Semanas 4, 8, 12 y 24 posteriores al tratamiento
2) Durante el curso del tratamiento del estudio hasta 28 días después de la última dosis del tratamiento del estudio.

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

Yes

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

Yes

E.6.13.1

Other scope of the trial description

Anti-viral activity

Actividad anti-viral

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

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

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

Poland

Spain

Taiwan

E.8.7

Trial has a data monitoring committee

Yes

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

UVUP

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

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

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)

None: Subject's care post-trial to be managed by their own physician.

Ninguno: El cuidado del sujeto después del ensayo debe ser manejado por su propio médico.

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

2018-02-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-01-17

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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