Clinical Trials Register

Summary
EudraCT Number:	2021-005132-33
Sponsor's Protocol Code Number:	73763989PAHPB2008
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-02-24
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2021-005132-33

A.3

Full title of the trial

A Phase 2 Open-label Trial to Evaluate Safety, Efficacy, Tolerability, and Pharmacodynamics of a Combination of JNJ-73763989, Nucleos(t)ide Analogs, and a PD-1 inhibitor in Chronic Hepatitis B Patients.

Plataforma: "Estudio Plataforma para evaluar la eficacia y seguridad de las intervenciones en pacientes con infección crónica de hepatitis B" Apéndice específico de intervención:
Estudio abierto en fase II para evaluar la seguridad, la eficacia, la tolerabilidad y la farmacodinamia de la combinación de JNJ-73763989, análogos de nucleós(t)idos y un inhibidor de PD-1 en pacientes con hepatitis B crónica.

A.3.1

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

A Clinical Study to evaluate the effects of a Combination of JNJ-73763989, Nucleos(t)ide Analogs, and a PD-1 inhibitor in Chronic Hepatitis B Patients.

Un estudio clínico para evaluar los efectos de una combinación de JNJ-73763989, análogos de nucleos(t)idos y un inhibidor de PD-1 en pacientes con hepatitis B crónica.

A.3.2

Name or abbreviated title of the trial where available

73763989PAHPB2008- OCTOPUS-1

A.4.1

Sponsor's protocol code number

73763989PAHPB2008

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 Research and Development 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, S.A.
B.5.2	Functional name of contact point	Global Development
B.5.3	Address:
B.5.3.1	Street Address	Pº de las Doce Estrellas, 5-7
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28042
B.5.3.4	Country	Spain
B.5.4	Telephone number	0034647309639
B.5.5	Fax number	0034637309639
B.5.6	E-mail	cgonz130@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.3.2	Product code	JNJ-73763989
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not yet assigned
D.3.9.2	Current sponsor code	JNJ-73763989
D.3.9.3	Other descriptive name	JNJ-73763989
D.3.9.4	EV Substance Code	SUB197801
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	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.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	OPDIVO 10 mg/mL concentrate for solution for infusion.
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol-Myers Squibb Pharma EEIG
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	Concentrate for 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	Nivolumab
D.3.9.3	Other descriptive name	Nivolumab
D.3.9.4	EV Substance Code	SUB122750
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	10
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	Yes
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 B Virus Infection

Infección crónica por el virus de la hepatitis B

E.1.1.1

Medical condition in easily understood language

Chronic Hepatitis B Virus Infection

Infección crónica por 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	20.1
E.1.2	Level	PT
E.1.2	Classification code	10008910
E.1.2	Term	Chronic hepatitis B
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

To evaluate efficacy of the study intervention, based on HBsAg levels at FU Week 24.

Evaluar la eficacia del tratamiento del estudio de acuerdo con los niveles de HBsAg en la semana 24 de seguimiento.

E.2.2

Secondary objectives of the trial

1. To characterize the safety and tolerability of the study intervention.
2. To evaluate efficacy in terms of changes in HBsAg levels from baseline over time during the study intervention and follow-up periods.
3. To evaluate efficacy in terms of HBsAg seroclearance/seroconversion during the study intervention and follow-up periods.
4. To evaluate the efficacy as measured by blood markers during the study intervention and follow-up period.
5. To evaluate the frequency of virologic breakthrough throughout the study.
6. To evaluate the pharmacokinetics of JNJ-3989 and optionally of NA and/or nivolumab.

1. Caracterizar la seguridad y tolerabilidad del tratamiento del estudio.
2. Evaluar la eficacia en cuanto a los cambios en el tiempo de los niveles de HBsAg respecto al momento de referencia durante el tratamiento del estudio y los periodos de seguimiento.
3. Evaluar la eficacia en cuanto a aclaramiento sérico/seroconversión de HBsAg durante el tratamiento del estudio y los periodos de seguimiento (como se define en Definiciones de términos).
4. Evaluar la eficacia, determinada a partir de marcadores sanguíneos (como el ADN del VHB y el HBeAg), durante el tratamiento del estudio y los periodos de seguimiento.
5.Evaluar la frecuencia de progresión virológica a lo largo del estudio.
6.Evaluar la farmacocinética (FC) de JNJ-3989 (es decir, JNJ-3924 y JNJ-3976) y, opcionalmente, de AN o nivolumab.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

A01. Adult male or female participants ≥18 (or the legal age of consent in the jurisdiction in which the study is taking place) to <56 years of age.
M02. Participants must be medically stable based on physical examination, medical history, vital signs, and 12-lead ECG performed at screening.
A03. Participants must have chronic HBV infection.
M04. Participants must have a body mass index between 18.0 and 30.0 kg/m2, extremes included.
A05. Participants must sign a Master ICF and must sign the ICF specific for this intervention cohort, indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study.

Please refer to the study protocol for a full list of inclusion criteria.

A01. Varones o mujeres de ≥18 años de edad (o la mayoría de edad legal para el consentimiento en la jurisdicción en la que tenga lugar el estudio) hasta < 56 años.
M02.Pacientes clínicamente estables de acuerdo con la exploración física, la historia clínica, las constantes vitales y el ECG de 12 derivaciones efectuado en la selección.
A03. Los participantes deben tener una infección crónica por VHB.
M04. Los participantes deben tener un índice de masa corporal entre 18,0 y 30,0 kg/m2, ambos incluidos.
A05. Los participantes deben firmar un DCI general y el DCI específico para esta cohorte de intervención, indicando que él o ella entiende el propósito y los procedimientos requeridos para el estudio y está dispuesto a participar en el estudio.

Consulte el protocolo del estudio para obtener una lista completa de los criterios de inclusión.

E.4

Principal exclusion criteria

A01. Participants with evidence of hepatitis A virus infection, HCV infection, hepatitis D virus infection, hepatitis E virus infection, or HIV-1 or HIV-2 infection at screening.
A02. Participants with evidence of hepatic decompensation at any time point prior to or at the time of screening.
M03. History or evidence of clinical signs or symptoms of hepatic decompensation.
M04. Participants with evidence of liver disease of non-HBV etiology.
A05. Participants with history or signs of cirrhosis or portal hypertension or signs of hepatocellular carcinoma (HCC) or clinically relevant renal
abnormalities.

Please refer to the study protocol for a full list of exclusion criteria.

A01. Participantes con evidencia de infección por el virus de la hepatitis A, infección por el VHC, infección por el virus de la hepatitis D, infección por el virus de la hepatitis E o infección por el VIH-1 o el VIH-2 en la selección.
A02. Participantes con evidencia de descompensación hepática en cualquier momento antes o en el momento de la selección.
M03. Antecedentes o evidencia de signos o síntomas clínicos de descompensación hepática.
M04. Participantes con evidencia de enfermedad hepática de etiología no relacionada con el VHB.
A05. Participantes con antecedentes o signos de cirrosis o hipertensión portal o signos de carcinoma hepatocelular (CHC) o insuficiencia renal clínicamente relevante

E.5 End points

E.5.1

Primary end point(s)

Proportion of participants who achieve HBsAg seroclearance at FU Week 24.

Proporción de participantes que logran el aclaramiento serológico de HBsAg en la semana 24 de FU.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 24.

Semana 24.

E.5.2

Secondary end point(s)

1a. Proportion of participants who experienced AEs of interest.
1b. Safety profile of JNJ-3989 with nivolumab throughout the study.

2a. Change from baseline in HBsAg levels during the study intervention and follow-up periods.
2b. Proportion of participants with HBsAg levels below/above different cut-offs over time.

3a. Proportion of participants with HBsAg seroclearance/seroconversion during the study intervention and follow-up periods.
3b. Time to achieve HBsAg seroclearance/seroconversion.

4a. Change from baseline in HBV DNA levels during the study intervention and follow-up periods.
4b. Proportion of participants with HBV DNA and HBeAg levels below/above different cut-offs over time.

5. Proportion of participants with virological breakthrough throughout the study.

6a. PK parameters of JNJ-3989.
6b. Optionally, PK parameters of NA and/or nivolumab.

1a. Proporción de participantes que experimentaron EA de interés.
1b. Perfil de seguridad de JNJ-3989 con nivolumab durante todo el estudio.

2a. Cambio desde el inicio en los niveles de HBsAg durante la intervención del estudio y los períodos de seguimiento.
2b. Proporción de participantes con niveles de HBsAg por debajo o por encima de diferentes puntos de corte a lo largo del tiempo.

3a. Proporción de participantes con aclarado sérico/seroconversión de HBsAg durante la intervención del estudio y los períodos de seguimiento.
3b. Tiempo para lograr la aclarado sérico/seroconversión de HBsAg.

4a. Cambio desde el inicio en los niveles de ADN del VHB durante la intervención del estudio y los períodos de seguimiento.
4b. Proporción de participantes con niveles de ADN del VHB y HBeAg por debajo o por encima de diferentes puntos de corte a lo largo del tiempo.

5. Proporción de participantes con recaída virológica a lo largo del estudio.

6a. Parámetros PK de JNJ-3989.
6b. Opcionalmente, parámetros PK de NA y/o nivolumab.

E.5.2.1

Timepoint(s) of evaluation of this end point

Throughout the duration of the study.

A lo largo de la duración 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

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

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)

Yes

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

Canada

Czechia

France

Italy

Malaysia

Russian Federation

Spain

Taiwan

Turkey

United Kingdom

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

Ultima visita del ultimo paciente

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

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)

Participants will be instructed that study intervention will not be made available to them after they have completed/discontinued study intervention and that they should return to their primary physician to determine standard of care.

A los pacientes se les indicará que la medicación del estudio no estará disponible para ellos una vez que finalicen el estudio o discontinuen la medicacion de estudio y que tendrán que acudir a sus médicos de familia/ general para decidir su tratamiento

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

2022-05-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-05-04

P. End of Trial
P.	End of Trial Status	Ongoing

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials