Clinical Trials Register

Summary
EudraCT Number:	2021-005132-33
Sponsor's Protocol Code Number:	73763989PAHPB2008
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-03-24
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

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

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.

Studio in aperto di fase 2 volto a valutare sicurezza, efficacia, tollerabilità e farmacodinamica di una combinazione di JNJ-73763989, analoghi nucleos(t)idici e un inibitore di PD-1 in pazienti con epatite B cronica.

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.

Studio clinico volto a valutare gli effetti di una combinazione di JNJ-73763989, analoghi nucleos(t)idici e un inibitore di PD-1 in pazienti con epatite B cronica.

A.3.2

Name or abbreviated title of the trial where available

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.4.1	Name of organisation providing support	Janssen Cilag SpA
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Janssen-Cilag International N.V.
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
B.5.3.4	Country	Netherlands
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-73763989
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.3.9.2	Current sponsor code	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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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.3.1	Product name	Nivolumab
D.3.2	Product code	[Nivolumab]
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.3.9.2	Current sponsor code	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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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

Epatite B cronica infezione da virus

E.1.1.1

Medical condition in easily understood language

Chronic Hepatitis B Virus Infection

Epatite B cronica infezione da 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	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.

Valutare l’efficacia del trattamento dello studio in base ai livelli di HBsAg alla Settimana 24 di follow-up (Settimana 24 di FU).

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. Caratterizzare la sicurezza e la tollerabilità del trattamento dello studio.
2. Valutare l’efficacia in termini di cambiamenti nei livelli di HBsAg rispetto al basale nel tempo durante i periodi di trattamento e di follow-up dello studio.
3. Valutare l’efficacia in termini di clearance sierica/sieroconversione di HBsAg durante i periodi di trattamento e di follow-up dello studio
4. Valutare l’efficacia come misurata dai marcatori ematici (come il DNA dell’HBV e HBeAg) durante i periodi di trattamento e di follow-up dello studio
5. Valutare la frequenza di breakthrough virologico durante lo studio.
6. Valutare la farmacocinetica (PK) di JNJ-3989 e in modo facoltativo di NA e/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. Partecipanti adulti di sesso maschile o femminile di età compresa tra >=18 anni (o l’età legale del consenso nella giurisdizione in cui si svolge lo studio) e <56 anni.
M02. I partecipanti devono essere clinicamente stabili in base ai risultati allo screening dell’esame obiettivo, dell’anamnesi, della misurazione dei segni vitali e dell’ECG a 12 derivazioni.
A03. I partecipanti devono avere un’infezione cronica da virus dell’epatite B (HBV)
M04. Avere un indice di massa corporea compreso tra 18,0 e 30,0 kg/m2, estremi inclusi
A05. I partecipanti devono firmare un modulo di consenso informato (ICF) principale e devono firmare un ICF specifico per questa coorte di trattamento, che indichi che il partecipante comprende lo scopo e le procedure richieste per lo studio ed è disposto a partecipare allo studio.

Fare riferimento al protocollo di studio per un elenco completo dei criteri di inclusione.

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. Partecipanti con evidenza di infezione da virus dell’epatite A, infezione da HCV, infezione da HDV, infezione da virus dell’epatite E, o infezione da HIV-1 o HIV-2 allo screening.
A02. Partecipanti con evidenza di scompenso epatico in qualsiasi punto temporale prima o al momento dello screening
M03. Anamnesi o evidenza di segni o sintomi clinici di scompenso epatico
M04. Partecipanti con evidenza di malattia epatica di eziologia non HBV
A05. Partecipanti con anamnesi o segni di cirrosi o ipertensione portale o segni di carcinoma epatocellulare (HCC) o anomalie renali clinicamente rilevanti

Fare riferimento al protocollo di studio per un elenco completo dei criteri di esclusione.

E.5 End points

E.5.1

Primary end point(s)

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

Percentuale di partecipanti che ottengono clearance sierica dell’HBsAg alla Settimana 24 di FU.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 24.

Settimana 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. Percentuale di partecipanti che ha manifestato eventi avversi (EA) di interesse.
1b. Profilo di sicurezza di JNJ-3989 con nivolumab durante lo studio

2a. Cambiamento rispetto al basale nei livelli di HBsAg durante i periodi di trattamento e di follow-up dello studio.
2b. Percentuale di partecipanti con livelli di HBsAg al di sotto/al di sopra di valori soglia nel tempo.

3a. Percentuale di partecipanti con clearance sierica/sieroconversione di HBsAg durante i periodi di trattamento e di follow-up dello studio.
3b. Tempo necessario per ottenere clearance sierica/sieroconversione di HBsAg

4a. Cambiamento rispetto al basale nei livelli di DNA dell’HBV durante i periodi di trattamento e di follow-up dello studio.
4b. Percentuale di partecipanti con livelli di DNA dell’HBV e HBeAg al di sotto/al di sopra di valori soglia diversi nel tempo.

5. Percentuale di partecipanti con breakthrough virologico durante lo studio.

6a. Parametri PK di JNJ-3989
6b. In modo facoltativo, i parametri PK di NA e/o nivolumab.

E.5.2.1

Timepoint(s) of evaluation of this end point

Throughout the duration of the study.

Per tutta la durata dello studio.

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

Information not present in EudraCT

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

Malaysia

Russian Federation

Taiwan

Turkey

Czechia

France

Italy

United Kingdom

Spain

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:

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.

Ai partecipanti verrà detto che l'intervento dello studio non sarà messo a loro disposizione dopo aver completato/interrotto l'intervento dello studio e che dovrebbero tornare dal proprio medico di base per determinare lo standard di cura.

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

2022-05-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-03-08

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

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