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Clinical Trial Results:
A Phase 2 Randomized, Open-label, Parallel-group, Multicenter Study to Assess Intrahepatic and PeripheralChanges of Immunologic and Virologic Markers in Response to Combination Regimens Containing JNJ-73763989 and Nucleos(t)ide Analog With or Without JNJ-56136379 in Patients With Chronic Hepatitis B Virus Infection

Summary
EudraCT number	2019-004475-39
Trial protocol	BE FR DE PL IT
Global end of trial date	01 Sep 2024

Results information
Results version number	v1(current)
This version publication date	11 Apr 2025
First version publication date	11 Apr 2025
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

73763989HPB2003

ISRCTN number

US NCT number

NCT04585789

WHO universal trial number (UTN)

Sponsor organisation name

Janssen Research & Development, a division of Janssen Pharmaceutica NV

Sponsor organisation address

Janssen Research & Development, a division of Janssen Pharmaceutica NV, Beerse, Belgium, 2340

Public contact

Clinical Registry Group, Janssen Research & Development, a division of Janssen Pharmaceutica NV, ClinicalTrialsEU@its.jnj.com

Scientific contact

ClinicalTrialsEU@its.jnj.com, Janssen Research & Development, a division of Janssen Pharmaceutica NV, ClinicalTrialsEU@its.jnj.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

01 Sep 2024

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

01 Sep 2024

Was the trial ended prematurely?

Main objective of the trial

The main objective of this study was to assess changes in intrahepatic hepatitis B surface antigen (HBsAg) between baseline and on-treatment liver biopsy in Panels 1 and 2 and to assess changes in drug concentrations over time in Panel 3 during JNJ-73763989 (JNJ-3989) treatment-based combination treatment.

Protection of trial subjects

This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practices and applicable regulatory requirements.

Background therapy

Evidence for comparator

Actual start date of recruitment

11 Mar 2021

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Belgium: 2

Country: Number of subjects enrolled

Canada: 5

Country: Number of subjects enrolled

Germany: 1

Country: Number of subjects enrolled

France: 5

Country: Number of subjects enrolled

United Kingdom: 1

Country: Number of subjects enrolled

Italy: 5

Country: Number of subjects enrolled

New Zealand: 3

Country: Number of subjects enrolled

Poland: 1

Country: Number of subjects enrolled

United States: 1

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Nucleos(t)ide analog (NA) treatment completion criteria (alanine aminotransferase [ALT] less than [<]3*upper limit of normal[ULN], HB virus deoxyribonucleic acid [HBV DNA] <lower limit of quantification [LLOQ]:20 International Units per milliliter [IU/mL], HBeAg negative & HB surface antigen [HBsAg] <10 IU/mL).

Screening details

Per protocol amendment (PA) 5 (01 October 2021), all subjects stopped JNJ-56136379 (JNJ-6379) treatment and continued treatment with JNJ-73763989 (JNJ-3989) plus nucleos(t)ide analog (NA; ETV, TD, or TAF) plus optional pegylated interferon alpha-2a (PegIFN-alpha2a). Study consisted of 3 phases: screening phase, OL intervention phase and FU phase.

Period 1 title

Open Label(OL) Phase: Week 1 to Week 48

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

OL Phase: Panel 1

Arm description

Prior to PA 5, subjects received either JNJ-3989 200 milligrams (mg) subcutaneous(SC) injection every 4 weeks(Q4W) from Day 1 (Week 1) to Week 44+JNJ-6379 250 mg once daily(QD)+NA (ETV 0.5 mg/TD 245 mg/TAF 25 mg) QD from Day 1 (Week 1) to Week 48 or JNJ-3989 200 mg SC injection Q4W from Day 1 (Week 1) to Week 44+NA (ETV 0.5 mg/TD 245 mg/TAF 25 mg) QD from Day 1 (Week 1) to Week 48. After PA 5, subjects stopped JNJ-6379 and continued JNJ-3989+NA. With separate consent, subjects received optional treatment: PegIFN-alpha-2a 180 micrograms(mcg) SC injection once weekly(QW) post Week 40 liver biopsy for either 12 or 24 weeks (anytime between study Week 40 to 72) at investigator's discretion. At end of treatment Week 48, all subjects entered FU phase and stopped JNJ-3989/JNJ-6379 and NA (if NA treatment completion criteria was met as per Week 44 laboratory tests). If NA treatment completion criteria were not met at Week 48, NA was continued till FU phase end (study Week 96).

Arm type

Experimental

Investigational medicinal product name

JNJ-73763989

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects received JNJ-73763989 200 mg SC injection once every 4 weeks from Day 1 up to Week 44.

Investigational medicinal product name

JNJ-56136379

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received JNJ-56136379 250 mg SC injection QD from Day 1 up to Week 48.

Investigational medicinal product name

Entecavir

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received entecavir 0.5 mg tablet QD from Day 1 up to Week 48.

Investigational medicinal product name

Tenofovir Disoproxil

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received tenofovir disoproxil 245 mg tablet QD from Day 1 up to Week 48.

Investigational medicinal product name

Tenofovir Alafenamide

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received tenofovir alafenamide 25 mg tablet QD from Day 1 up to Week 48.

Investigational medicinal product name

PegIFN-alpha-2a

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects received PegIFN-alpha-2a 180 mcg SC injection QW for either 12 or 24 weeks.

OL Phase: Panel 2

Arm description

Prior to PA 5, subjects received either JNJ-3989 200 mg SC injection Q4W from Day 1 (Week 1) to Week 44 + JNJ-6379 250 mg QD and NA treatment (ETV 0.5 mg/TD 245 mg/TAF 25 mg) QD from Day 1 (Week 1) to Week 48, or JNJ-3989 200 mg SC injection Q4W from Day 1 (Week 1) to Week 44 + NA (ETV 0.5 mg/TD 245 mg/TAF 25 mg) QD from Day 1 (Week 1) to Week 48. After PA 5, subjects discontinued JNJ-6379 and continued JNJ-3989 + NA. With separate consent, subjects received optional treatment with PegIFNalpha-2a 180 mcg SC injection QW after Week 40 liver biopsy for either 12 or 24 weeks (anytime between study Week 40 to 72) at investigator's discretion. At end of treatment Week 48, all subjects entered FU phase and stopped JNJ-3989/JNJ-6379 and NA (if NA treatment completion criteria was met as per Week 44 laboratory tests). If NA treatment completion criteria were not met at Week 48, NA was continued till FU phase end (study Week 96).

Arm type

Experimental

Investigational medicinal product name

JNJ-73763989

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects received JNJ-73763989 200 mg SC injection once every 4 weeks from Day 1 up to Week 44.

Investigational medicinal product name

JNJ-56136379

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received JNJ-56136379 250 mg SC injection QD from Day 1 up to Week 48.

Investigational medicinal product name

Entecavir

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received entecavir 0.5 mg tablet QD from Day 1 up to Week 48.

Investigational medicinal product name

Tenofovir Disoproxil

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received tenofovir disoproxil 245 mg tablet QD from Day 1 up to Week 48.

Investigational medicinal product name

Tenofovir Alafenamide

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received tenofovir alafenamide 25 mg tablet QD from Day 1 up to Week 48.

Investigational medicinal product name

PegIFN-alpha-2a

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects received PegIFN-alpha-2a 180 mcg SC injection QW for either 12 or 24 weeks.

OL Phase: Panel 3

Arm description

After PA 5, subjects received either JNJ-3989 200 mg SC injection Q4W from Day 1 (Week 1 to Week 44) + JNJ-6379 250 mg QD and NA treatment (ETV 0.5 mg/TD 245 mg/TAF 25 mg) QD from Day 1 (Week 1) to Week 48, or JNJ-3989 200 mg SC injection Q4W from Day 1 (Week 1) to Week 44 + NA (ETV 0.5 mg/TD 245 mg/TAF 25 mg) QD from Day 1 (Week 1) to Week 48. After PA 5, subjects discontinued JNJ-6379 and continued JNJ-3989 + NA. With separate consent, subjects received optional treatment with PegIFNalpha-2a 180 mcg SC injection QW after Week 40 liver biopsy for either 12 or 24 weeks (anytime between study Week 40 to 72) at investigator's discretion. At end of treatment Week 48, all subjects entered FU phase and stopped JNJ-3989/JNJ-6379 and NA (if NA treatment completion criteria was met as per Week 44 laboratory tests). If NA treatment completion criteria were not met at Week 48, NA was continued till FU phase end (study Week 96).

Arm type

Experimental

Investigational medicinal product name

JNJ-73763989

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects received JNJ-73763989 200 mg SC injection once every 4 weeks from Day 1 up to Week 44.

Investigational medicinal product name

Entecavir

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received entecavir 0.5 mg tablet QD from Day 1 up to Week 48.

Investigational medicinal product name

PegIFN-alpha-2a

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects received PegIFN-alpha-2a 180 mcg SC injection QW for either 12 or 24 weeks.

Investigational medicinal product name

Tenofovir Alafenamide

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received tenofovir alafenamide 25 mg tablet QD from Day 1 up to Week 48.

Investigational medicinal product name

Tenofovir Disoproxil

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received tenofovir disoproxil 245 mg tablet QD from Day 1 up to Week 48.

Number of subjects in period 1	OL Phase: Panel 1	OL Phase: Panel 2	OL Phase: Panel 3
Started	10	10	4
Completed	10	10	4

Period 2 title

Follow-up (FU) Phase: Week 48 to 96

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Follow-up Phase: Panel 1

Arm description

After completion of open-label phase (up to 48 weeks) all subjects (with HBeAg positive and not currently treated) enrolled prior to PA 5, entered FU phase & stopped all study drugs including NA treatment, but NA treatment continued till end of FU (study Week 96), if NA treatment completion criteria (ALT: <3*ULN, HBV DNA <LLOQ:20 IU/mL, HBeAg negative and HBsAg<10 IU/mL) was not met at Week 48. Subjects on treatment with optional PegIFN-alpha-2a 180 mcg SC injection QW after Week 40 liver biopsy but had not met NA treatment completion criteria at Week 48, were assessed at end of treatment with PegIFN-α2a (study Week 60 or 72) and stopped NA, if NA treatment completion criteria were met. Subjects who met NA treatment completion criteria (at Week 48) were monitored Q4W in FU phase. If NA-retreatment criteria:HBV DNA >20,000 IU/mL, HBV DNA >2,000 IU/mL but <20,000 IU/mL & ALT>5*ULN was met, NA retreatment was started.

Arm type

Experimental

Investigational medicinal product name

Entecavir

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received entecavir 0.5 mg tablet QD from Day 1 up to Week 48.

Investigational medicinal product name

Tenofovir Alafenamide

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received tenofovir alafenamide 25 mg tablet QD from Day 1 up to Week 48.

Investigational medicinal product name

Tenofovir Disoproxil

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received tenofovir disoproxil 245 mg tablet QD from Day 1 up to Week 48.

Follow-up Phase: Panel 2

Arm description

After completion of open-label phase (up to 48 weeks) all subjects (with HBeAg negative & virologically suppressed by ETV, TD, or TAF treatment) enrolled prior to PA 5, entered FU phase & stopped all study drugs including NA treatment, but NA treatment continued till end of FU (study Week 96), if NA treatment completion criteria (ALT: <3*ULN, HBV DNA <LLOQ:20 IU/mL, HBeAg negative and HBsAg<10 IU/mL) was not met at Week 48. Subjects who were on treatment with optional PegIFN-alpha-2a 180 mcg SC injection QW after Week 40 liver biopsy but had not met NA treatment completion criteria at Week 48, were assessed at the end of treatment with PegIFN-α2a (study Week 60 or 72) and stopped NA, if the NA treatment completion criteria were met. Subjects who met NA treatment completion criteria (at Week48) were monitored Q4W in FU phase. If NA-retreatment criteria (HBV DNA >20,000 IU/mL, HBV DNA >2,000 IU/mL but <20,000 IU/mL & ALT >5*ULN) was met, NA retreatment was started.

Arm type

Experimental

Investigational medicinal product name

Entecavir

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received entecavir 0.5 mg tablet QD from Day 1 up to Week 48.

Investigational medicinal product name

Tenofovir Alafenamide

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received tenofovir alafenamide 25 mg tablet QD from Day 1 up to Week 48.

Investigational medicinal product name

Tenofovir Disoproxil

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received tenofovir disoproxil 245 mg tablet QD from Day 1 up to Week 48.

Follow-up Phase: Panel 3

Arm description

After completion of open-label phase (up to 48 weeks) subjects (HBeAg positive or negative & were either not currently treated or virologically suppressed by ETV or TD treatment) enrolled after PA 5, entered FU phase & stopped all study drugs including NA, but NA treatment continued till end of FU (study Week 96), if NA treatment completion criteria ([ALT <3*ULN, HBV DNA <LLOQ; 20 IU/mL, HBeAg negative and HBsAg <10 IU/mL]) was not met at Week 48. Subjects on treatment with optional PegIFNalpha-2a 180 mcg SC injection QW post Week 40 liver biopsy but had not met NA treatment completion criteria at Week 48, were assessed at end of treatment with PegIFN-α2a (study Week 60 or 72) & stopped NA, if NA treatment completion criteria were met. Subjects who met NA treatment completion criteria (at Week 48) were monitored Q4W in FU phase. If NA-retreatment criteria (HBV DNA >20,000 IU/mL, HBV DNA >2,000 IU/mL but <20,000 IU/mL & ALT >5*ULN) was met, NA retreatment was started.

Arm type

Experimental

Investigational medicinal product name

Entecavir

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received entecavir 0.5 mg tablet QD from Day 1 up to Week 48.

Investigational medicinal product name

Tenofovir Disoproxil

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received tenofovir disoproxil 245 mg tablet QD from Day 1 up to Week 48.

Investigational medicinal product name

Tenofovir Alafenamide

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received tenofovir alafenamide 25 mg tablet QD from Day 1 up to Week 48.

Number of subjects in period 2	Follow-up Phase: Panel 1	Follow-up Phase: Panel 2	Follow-up Phase: Panel 3
Started	10	10	4
Completed	8	10	4
Not completed	2	0	0
Consent withdrawn by subject	1	-	-
Lost to follow-up	1	-	-

Baseline characteristics

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Reporting group title

OL Phase: Panel 1

Reporting group description

Reporting group title

OL Phase: Panel 2

Reporting group description

Reporting group title

OL Phase: Panel 3

Reporting group description

Reporting group values	OL Phase: Panel 1	OL Phase: Panel 2	OL Phase: Panel 3	Total
Number of subjects	10	10	4
Age Categorical
Units: Subjects
Age continuous
Units: Years
arithmetic mean (standard deviation)	33.4 ( 14.73 )	43.4 ( 12.63 )	42 ( 12.73 )	-
Gender categorical
Units: Subjects
Male	5	5	4	14
Female	5	5	0	10
Age Categorical
Units: Subjects
Children (2-11 years)	0	0	0	0
Adolescents (12-17 years)	0	0	0	0
Adults (18-64 years)	10	10	4	24
From 65 to 84 years	0	0	0	0
85 years and over	0	0	0	0

Subject analysis set title

Panel 1

Subject analysis set type

Per protocol

Subject analysis set description

Prior to PA 5, subjects received either JNJ-3989 200 milligrams (mg) subcutaneous(SC) injection every 4 weeks(Q4W) from Day 1 (Week 1) to Week 44+JNJ-6379 250 mg once daily(QD)+NA (ETV 0.5 mg/TD 245 mg/TAF 25 mg) QD from Day 1 (Week 1) to Week 48 or JNJ-3989 200 mg SC injection Q4W from Day 1 (Week 1) to Week 44+NA (ETV 0.5 mg/TD 245 mg/TAF 25 mg) QD from Day 1 (Week 1) to Week 48. After PA 5, subjects stopped JNJ-6379 and continued JNJ-3989+NA. With separate consent, subjects received optional treatment: PegIFN-alpha-2a 180 micrograms(mcg) SC injection once weekly(QW) post Week 40 liver biopsy for either 12 or 24 weeks (anytime between study Week 40 to 72) at investigator's discretion. At end of treatment Week 48, all subjects entered FU phase and stopped JNJ-3989/JNJ-6379 and NA, if NA treatment completion criteria was met as per Week 44 laboratory tests. If NA treatment completion criteria were not met at Week 48, NA was continued till FU phase end (study Week 96).

Subject analysis set title

Panel 2

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Panel 3

Subject analysis set type

Per protocol

Subject analysis set description

After PA 5, subjects received either JNJ-3989 200 mg SC injection Q4W from Day 1 (Week 1 to Week 44) + JNJ-6379 250 mg QD and NA treatment (ETV 0.5 mg/TD 245 mg/TAF 25 mg) QD from Day 1 (Week 1) to Week 48, or JNJ-3989 200 mg SC injection Q4W from Day 1 (Week 1) to Week 44 + NA (ETV 0.5 mg/ TD 245 mg/TAF 25 mg) QD from Day 1 (Week 1) to Week 48. After PA 5, subjects discontinued JNJ-6379 and continued JNJ-3989 + NA. With separate consent, subjects received optional treatment with PegIFNalpha- 2a 180 mcg SC injection QW after Week 40 liver biopsy for either 12 or 24 weeks (anytime between study Week 40 to 72) at investigator's discretion. At end of treatment Week 48, all subjects entered FU phase and stopped JNJ-3989/JNJ-6379 and NA (if NA treatment completion criteria was met as per Week 44 laboratory tests). If NA treatment completion criteria were not met at Week 48, NA was continued till FU phase end (study Week 96).

Subject analysis sets values	Panel 1	Panel 2	Panel 3
Number of subjects	10	10	4
Age Categorical
Units: Subjects
Age continuous
Units: Years
arithmetic mean (standard deviation)	0 ( )	0 ( )	0 ( )
Gender categorical
Units: Subjects
Male	0	0	0
Female	0	0	0
Age Categorical
Units: Subjects
Children (2-11 years)	0	0	0
Adolescents (12-17 years)	0	0	0
Adults (18-64 years)	0	0	0
From 65 to 84 years	0	0	0
85 years and over	0	0	0

End points

Top of page

Reporting group title

OL Phase: Panel 1

Reporting group description

Reporting group title

OL Phase: Panel 2

Reporting group description

Reporting group title

OL Phase: Panel 3

Reporting group description

Reporting group title

Follow-up Phase: Panel 1

Reporting group description

Reporting group title

Follow-up Phase: Panel 2

Reporting group description

Reporting group title

Follow-up Phase: Panel 3

Reporting group description

Subject analysis set title

Panel 1

Subject analysis set type

Per protocol

Subject analysis set description

Prior to PA 5, subjects received either JNJ-3989 200 milligrams (mg) subcutaneous(SC) injection every 4 weeks(Q4W) from Day 1 (Week 1) to Week 44+JNJ-6379 250 mg once daily(QD)+NA (ETV 0.5 mg/TD 245 mg/TAF 25 mg) QD from Day 1 (Week 1) to Week 48 or JNJ-3989 200 mg SC injection Q4W from Day 1 (Week 1) to Week 44+NA (ETV 0.5 mg/TD 245 mg/TAF 25 mg) QD from Day 1 (Week 1) to Week 48. After PA 5, subjects stopped JNJ-6379 and continued JNJ-3989+NA. With separate consent, subjects received optional treatment: PegIFN-alpha-2a 180 micrograms(mcg) SC injection once weekly(QW) post Week 40 liver biopsy for either 12 or 24 weeks (anytime between study Week 40 to 72) at investigator's discretion. At end of treatment Week 48, all subjects entered FU phase and stopped JNJ-3989/JNJ-6379 and NA, if NA treatment completion criteria was met as per Week 44 laboratory tests. If NA treatment completion criteria were not met at Week 48, NA was continued till FU phase end (study Week 96).

Subject analysis set title

Panel 2

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Panel 3

Subject analysis set type

Per protocol

Subject analysis set description

After PA 5, subjects received either JNJ-3989 200 mg SC injection Q4W from Day 1 (Week 1 to Week 44) + JNJ-6379 250 mg QD and NA treatment (ETV 0.5 mg/TD 245 mg/TAF 25 mg) QD from Day 1 (Week 1) to Week 48, or JNJ-3989 200 mg SC injection Q4W from Day 1 (Week 1) to Week 44 + NA (ETV 0.5 mg/ TD 245 mg/TAF 25 mg) QD from Day 1 (Week 1) to Week 48. After PA 5, subjects discontinued JNJ-6379 and continued JNJ-3989 + NA. With separate consent, subjects received optional treatment with PegIFNalpha- 2a 180 mcg SC injection QW after Week 40 liver biopsy for either 12 or 24 weeks (anytime between study Week 40 to 72) at investigator's discretion. At end of treatment Week 48, all subjects entered FU phase and stopped JNJ-3989/JNJ-6379 and NA (if NA treatment completion criteria was met as per Week 44 laboratory tests). If NA treatment completion criteria were not met at Week 48, NA was continued till FU phase end (study Week 96).

Primary: Panel 1 and 2: Absolute Change From Baseline in the Percentage of Hepatitis B Surface Antigen (HBsAg) Hepatocytes at Week 40

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End point title

Panel 1 and 2: Absolute Change From Baseline in the Percentage of Hepatitis B Surface Antigen (HBsAg) Hepatocytes at Week 40 ^[1] ^[2]

End point description

Absolute change from baseline to on-treatment liver biopsy timepoint (Week 40) in terms of the percentage of HBsAg-positive hepatocytes (at Week 40) were reported. Intent-to-treat (ITT) population included subjects who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Subjects were analyzed according to study intervention they were randomly assigned or enrolled. Here "N" (Number of subjects analysed) signifies the number of subjects that were evaluable for this endpoint. Data for this endpoint was planned to be collected and analyzed for Panels 1 and 2 alone.

End point type

Primary

End point timeframe

Baseline, Week 40

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No inferential statistics was done. Only descriptive statistics was performed.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Data for this endpoint was planned to be collected and analyzed for Panels 1 and 2 alone.

End point values	OL Phase: Panel 1	OL Phase: Panel 2
Number of subjects analysed	6	9
Units: percentage of HBsAg hepatocytes
arithmetic mean (confidence interval 80%)	-78.46 (-94.078 to -42.936)	-5.68 (-15.846 to -0.885)

No statistical analyses for this end point

Primary: Panel 3: Liver Concentrations of JNJ-73763989 (JNJ-73763976, JNJ-73763924 and M65; Deaminated Metabolite of JNJ-73763976) at Week 12

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End point title

Panel 3: Liver Concentrations of JNJ-73763989 (JNJ-73763976, JNJ-73763924 and M65; Deaminated Metabolite of JNJ-73763976) at Week 12 ^[3] ^[4]

End point description

Liver concentrations of JNJ-73763989 (JNJ-73763976, JNJ-73763924 and M65; Deaminated Metabolite of JNJ-73763976) at Week 12 were reported. ITT population included subjects who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Subjects were analyzed according to study intervention they were randomly assigned or enrolled. Data for this endpoint was planned to be collected and analyzed for Panel 3 alone.

End point type

Primary

End point timeframe

At Week 12 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No inferential statistics was done. Only descriptive statistics was performed.
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Data for this endpoint was planned to be collected and analyzed for Panel 3 alone.

End point values	OL Phase: Panel 3
Number of subjects analysed	4
Units: ng/g
arithmetic mean (standard deviation)
JNJ-73763976	3550.00 ( 1674.714 )
JNJ-73763924	87300.00 ( 31712.668 )
M65	66175.00 ( 26000.817 )

No statistical analyses for this end point

Primary: Panel 3: Liver Concentrations of JNJ-73763989 (JNJ-73763976, JNJ-73763924 and M65; Deaminated Metabolite of JNJ-73763976) at Week 40

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End point title

Panel 3: Liver Concentrations of JNJ-73763989 (JNJ-73763976, JNJ-73763924 and M65; Deaminated Metabolite of JNJ-73763976) at Week 40 ^[5] ^[6]

End point description

Liver concentrations of JNJ-73763989 (JNJ-73763976, JNJ-73763924 molecules of JNJ-73763989) and JNJ-87719164 (M65: determined metabolite of JNJ-73763976) at Week 40 were reported. ITT population included subjects who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Subjects were analyzed according to study intervention they were randomly assigned or enrolled. Here "N" (Number of subjects analysed) signifies the number of subjects that were evaluable for this endpoint. Data for this endpoint was planned to be collected and analyzed for Panel 3 alone.

End point type

Primary

End point timeframe

At Week 40 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No inferential statistics was done. Only descriptive statistics was performed.
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Data for this endpoint was planned to be collected and analyzed for Panel 3 alone.

End point values	OL Phase: Panel 3
Number of subjects analysed	3
Units: ng/g
arithmetic mean (standard deviation)
JNJ-73763976	5883.33 ( 2147.145 )
JNJ-73763924	208666.67 ( 66860.551 )
M65	133800.00 ( 50615.413 )

No statistical analyses for this end point

Primary: Panel 3: Plasma Concentration of JNJ-73763989 (JNJ-73763976, JNJ-73763924 and M65; Deaminated Metabolite of JNJ-73763976) at Week 12

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End point title

Panel 3: Plasma Concentration of JNJ-73763989 (JNJ-73763976, JNJ-73763924 and M65; Deaminated Metabolite of JNJ-73763976) at Week 12 ^[7] ^[8]

End point description

Plasma concentration of JNJ-73763989 (JNJ-73763976, JNJ-73763924 and M65; Deaminated Metabolite of JNJ-73763976) at Week 12 were reported. ITT population included subjects who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Subjects were analyzed according to study intervention they were randomly assigned or enrolled. Data for this endpoint was planned to be collected and analyzed for Panel 3 alone.

End point type

Primary

End point timeframe

At Week 12 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No inferential statistics was done. Only descriptive statistics was performed.
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Data for this endpoint was planned to be collected and analyzed for Panel 3 alone.

End point values	OL Phase: Panel 3
Number of subjects analysed	4
Units: nanograms per milliliter (ng/mL)
arithmetic mean (standard deviation)
JNJ-73763976	254.70 ( 123.841 )
JNJ-73763924	36.18 ( 22.667 )

No statistical analyses for this end point

Primary: Panel 3: Plasma Concentrations of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) at Week 40

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End point title

Panel 3: Plasma Concentrations of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) at Week 40 ^[9] ^[10]

End point description

Plasma concentrations of JNJ-73763989 (JNJ-73763976 and JNJ-73763924 molecules of JNJ-73763989) at Week 40 were reported. ITT population included subjects who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Subjects were analyzed according to study intervention they were randomly assigned or enrolled. Here "N" (Number of subjects analysed) signifies the number of subjects that were evaluable for this endpoint. Data for this endpoint was planned to be collected and analyzed for Panel 3 alone.

End point type

Primary

End point timeframe

At Week 40 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)

Notes
[9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No inferential statistics was done. Only descriptive statistics was performed.
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Data for this endpoint was planned to be collected and analyzed for Panel 3 alone.

End point values	OL Phase: Panel 3
Number of subjects analysed	3
Units: ng/mL
arithmetic mean (standard deviation)
JNJ-73763976	530.97 ( 176.408 )
JNJ-73763924	74.87 ( 12.788 )

No statistical analyses for this end point

Primary: Panel 3: Correlation of Liver Concentration to Plasma Concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) and Liver Concentration of M65 (Deaminated Metabolite of JNJ-73763976) to Liver Concentration JNJ-73763976 at Week 12

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End point title

Panel 3: Correlation of Liver Concentration to Plasma Concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) and Liver Concentration of M65 (Deaminated Metabolite of JNJ-73763976) to Liver Concentration JNJ-73763976 at Week 12 ^[11] ^[12]

End point description

Correlation of liver concentration to plasma concentration of JNJ-73763989 (JNJ-73763976 and liver concentration of M65 (Deaminated metabolite of JNJ-73763976) to liver concentration JNJ-73763976 at Week 12 were reported. ITT population included subjects who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Subjects were analyzed according to study intervention they were randomly assigned or enrolled. Data for this endpoint was planned to be collected and analyzed for Panel 3 alone.

End point type

Primary

End point timeframe

Week 12 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)

Notes
[11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No inferential statistics was done. Only descriptive statistics was performed.
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Data for this endpoint was planned to be collected and analyzed for Panel 3 alone.

End point values	OL Phase: Panel 3
Number of subjects analysed	4
Units: ratio
arithmetic mean (standard deviation)
JNJ-73763976 (liver to plasma concentration)	14.51 ( 4.725 )
JNJ-73763924 (liver to plasma concentration)	2844.26 ( 1265.202 )
M65 to JNJ-73763976(liver to liver concentration)	19.47 ( 3.267 )

No statistical analyses for this end point

Primary: Panel 3: Correlation of Liver to Plasma Concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) and Liver Concentration of M65 (Deaminated Metabolite of JNJ-73763976) to Liver Concentration JNJ-73763976 at Week 40

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End point title

Panel 3: Correlation of Liver to Plasma Concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) and Liver Concentration of M65 (Deaminated Metabolite of JNJ-73763976) to Liver Concentration JNJ-73763976 at Week 40 ^[13] ^[14]

End point description

Correlation of liver concentration to plasma concentration of JNJ-73763989 (JNJ-73763976 and liver concentration of M65 (Deaminated metabolite of JNJ-73763976) to liver concentration JNJ-73763976 at Week 40 were reported. ITT population included subjects who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Subjects were analyzed according to study intervention they were randomly assigned or enrolled. Here "N" (Number of subjects analysed) signifies the number of subjects that were evaluable for this endpoint. Data for this endpoint was planned to be collected and analyzed for Panel 3 alone.

End point type

Primary

End point timeframe

Week 40 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)

Notes
[13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No inferential statistics was done. Only descriptive statistics was performed.
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Data for this endpoint was planned to be collected and analyzed for Panel 3 alone.

End point values	OL Phase: Panel 3
Number of subjects analysed	3
Units: ratio
arithmetic mean (standard deviation)
JNJ-73763976	12.67 ( 7.269 )
JNJ-73763924	2847.66 ( 1034.033 )
M65 to JNJ-73763976 liver concentration	22.65 ( 1.407 )

No statistical analyses for this end point

Secondary: Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Hepatitis B Core Antigen Positive (HBcAg+) Hepatocytes at Week 40

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End point title

Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Hepatitis B Core Antigen Positive (HBcAg+) Hepatocytes at Week 40

End point description

Change from baseline in percentage of intrahepatic viral parameters HBcAg positive hepatocytes at Week 40 were reported. The percentage of HBcAg positive hepatocytes were derived as number of HBcAg positive hepatocytes*100 per total number of evaluated hepatocytes. ITT population included subjects who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Subjects were analyzed according to study intervention they were randomly assigned or enrolled. Here "N" (Number of subjects analyzed) signifies the number of subjects that were evaluable for this endpoint. Data for this endpoint was not planned to be collected and analyzed for Panel 3.

End point type

Secondary

End point timeframe

Baseline, Week 40

End point values	Panel 1	Panel 2
Number of subjects analysed	6	9
Units: percentage change of HBcAg + Hepatocytes
median (inter-quartile range (Q1-Q3))	-54.49 (-87.02 to -42.26)	0.03 (0.00 to 0.04)

No statistical analyses for this end point

Secondary: Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Covalently Closed Circular Deoxyribonucleic Acid Positive (cccDNA+) Hepatocytes at Week 40

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End point title

Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Covalently Closed Circular Deoxyribonucleic Acid Positive (cccDNA+) Hepatocytes at Week 40 ^[15]

End point description

Change from baseline in percentage of intrahepatic viral parameters: cccDNA positive hepatocytes were reported. The percentage of cccDNA-positive hepatocytes, were derived as number of cccDNA positive hepatocytes*100 per total number of evaluated hepatocytes. ITT population included subjects who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Subjects were analyzed according to study intervention they were randomly assigned or enrolled. Here "N" (Number of subjects analyzed) signifies the number of subjects that were evaluable for this endpoint. Data for this endpoint was not planned to be collected and analyzed for Panel 3.

End point type

Secondary

End point timeframe

Baseline, Week 40

Notes
[15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Data for this endpoint was not planned to be collected and analyzed for Panel 3.

End point values	OL Phase: Panel 1	OL Phase: Panel 2
Number of subjects analysed	4	4
Units: percentage change of cccDNA+ hepatocytes
median (inter-quartile range (Q1-Q3))	-4.50 (-40.88 to 12.97)	-2.40 (-22.84 to 7.57)

No statistical analyses for this end point

Secondary: Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: HBsAg Positive (HBsAg+) Hepatocytes at Week 40

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End point title

Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: HBsAg Positive (HBsAg+) Hepatocytes at Week 40 ^[16]

End point description

Change from baseline in percentage of intrahepatic viral parameter: HBsAg positive hepatocytes at Week 40 were reported. The percentage of HBsAg positive hepatocytes were derived as number of HBsAg positive hepatocytes * 100 per total number of evaluated hepatocytes. ITT population included subjects who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Subjects were analyzed according to study intervention they were randomly assigned or enrolled. Here "N" (Number of subjects analyzed) signifies the number of subjects that were evaluable for this endpoint. Data for this endpoint was not planned to be collected and analyzed for Panel 3.

End point type

Secondary

End point timeframe

Baseline, Week 40

Notes
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Data for this endpoint was not planned to be collected and analyzed for Panel 3.

End point values	OL Phase: Panel 1	OL Phase: Panel 2
Number of subjects analysed	6	9
Units: percentage change of HBsAg+ hepatocytes
median (inter-quartile range (Q1-Q3))	-92.38 (-95.65 to -73.37)	-14.19 (-21.11 to -7.01)

No statistical analyses for this end point

Secondary: Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Pre-genomic Ribonucleic Acid Positive (pgRNA+) Hepatocytes at Week 40

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End point title

Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Pre-genomic Ribonucleic Acid Positive (pgRNA+) Hepatocytes at Week 40 ^[17]

End point description

Change from baseline in percentage of intrahepatic viral Parameter: pgRNA positive hepatocytes at Week 40 were reported. The percentage of pgRNA-positive hepatocytes were derived as number of pgRNA positive hepatocytes*100 per total number of evaluated hepatocytes. ITT population included subjects who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Subjects were analyzed according to study intervention they were randomly assigned or enrolled. Here "N" (Number of subjects analyzed) signifies the number of subjects that were evaluable for this endpoint. Data for this endpoint was not planned to be collected and analyzed for Panel 3.

End point type

Secondary

End point timeframe

Baseline, Week 40

Notes
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Data for this endpoint was not planned to be collected and analyzed for Panel 3.

End point values	OL Phase: Panel 1	OL Phase: Panel 2
Number of subjects analysed	4	4
Units: percentage change of pgRNA + hepatocytes
median (inter-quartile range (Q1-Q3))	-81.23 (-86.19 to -74.14)	-6.74 (-15.81 to -2.01)

No statistical analyses for this end point

Secondary: Panel 1 and 2: Change From Baseline in Transcriptional Activity (Ratio of pg RNA/cccDNA) at Week 40

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End point title

Panel 1 and 2: Change From Baseline in Transcriptional Activity (Ratio of pg RNA/cccDNA) at Week 40 ^[18]

End point description

Change from baseline in transcriptional activity (ratio of pgRNA/cccDNA) at Week 40 were reported. ITT population included subjects who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Subjects were analyzed according to study intervention they were randomly assigned or enrolled. Here "N" (Number of subjects analyzed) signifies the number of subjects that were evaluable for this endpoint. Data for this endpoint was not planned to be collected and analyzed for Panel 3.

End point type

Secondary

End point timeframe

Baseline, Week 40

Notes
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Data for this endpoint was not planned to be collected and analyzed for Panel 3.

End point values	OL Phase: Panel 1	OL Phase: Panel 2
Number of subjects analysed	4	4
Units: ratio
median (inter-quartile range (Q1-Q3))	50.00 (49.07 to 58.83)	8.86 (-3.03 to 27.45)

No statistical analyses for this end point

Secondary: Panel 1, 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Silent Infected Hepatocytes at Week 40

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End point title

Panel 1, 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Silent Infected Hepatocytes at Week 40 ^[19]

End point description

Change from baseline in percentage of intrahepatic viral parameter: silent infected hepatocytes (that is infected hepatocytes without HBV transcription; cccDNA-positive/HBV RNA-negative hepatocytes) at Week 40 were reported. The percentage of silent infected hepatocytes (SIH), were derived as number of silent infected hepatocytes*100 per total number of evaluated hepatocytes. ITT population included subjects who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Subjects were analyzed according to study intervention they were randomly assigned or enrolled. Here "N" (Number of subjects analyzed) signifies the number of subjects that were evaluable for this endpoint. Data for this endpoint was not planned to be collected and analyzed for Panel 3.

End point type

Secondary

End point timeframe

Baseline, Week 40

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Data for this endpoint was not planned to be collected and analyzed for Panel 3.

End point values	OL Phase: Panel 1	OL Phase: Panel 2
Number of subjects analysed	4	4
Units: percent change of hepatocytes
median (inter-quartile range (Q1-Q3))	25.06 (21.40 to 31.63)	2.88 (-14.74 to 8.80)

No statistical analyses for this end point

Secondary: Panel 1, 2 and 3: Percentage of Subjects With HBsAg Seroclearance at Week 72 Without Restarting Nucleos(t)Ide Analog (NA) Treatment

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End point title

Panel 1, 2 and 3: Percentage of Subjects With HBsAg Seroclearance at Week 72 Without Restarting Nucleos(t)Ide Analog (NA) Treatment

End point description

Percentage of subjects with HBsAg seroclearance (defined as HBsAg < LLOQ: 0.05 IU/mL) at Week 72 without restarting NA treatment were reported. ITT population included subjects who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Subjects were analyzed according to study intervention they were randomly assigned or enrolled. Here "N" (Number of subjects analyzed) signifies the number of subjects that were evaluable for this endpoint.

End point type

Secondary

End point timeframe

At Week 72 (24 weeks after completion of all study drugs at Week 48)

End point values	Follow-up Phase: Panel 1	Follow-up Phase: Panel 2	Follow-up Phase: Panel 3
Number of subjects analysed	9	10	4
Units: Percentage of subjects
number (not applicable)	0	1	0

No statistical analyses for this end point

Secondary: Panel 1, 2 and 3: Percentage of Subjects With Sustained (Reduction) Serum HBsAg Response Per Definition 1 at Follow-up Week 48

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End point title

Panel 1, 2 and 3: Percentage of Subjects With Sustained (Reduction) Serum HBsAg Response Per Definition 1 at Follow-up Week 48

End point description

Percentage of subjects with sustained (reduction) serum HBsAg response per Definition 1 at follow-up Week 48 were reported. Sustained serum HBsAg response per definition 1 was defined as: for subjects with data for last follow-up visit (Follow-up Week 48 for subjects who did not receive PegIFN-alpha2a or received PegIFN-alpha2a and did not meet NA completion criteria, and last Follow-up visit for subjects who received PegIFN-alpha2a and stopped NA during Follow-up): subjects who had a >1 log decline in HBsAg response at last scheduled follow-up visit and had an HBsAg <1000 IU/mL at last scheduled follow-up visit, or for subjects without data at last follow-up visit: HBsAg values had a >2 log decline at second most recent visit or >1.5 log decline at latest visit (most recent value used) compared to baseline and had an HBsAg <1000 IU/mL at last available timepoint. ITT population analyzed. Subjects were analysed according to study intervention they were randomly assigned or enrolled.

End point type

Secondary

End point timeframe

Follow-up Week 48

End point values	Follow-up Phase: Panel 1	Follow-up Phase: Panel 2	Follow-up Phase: Panel 3
Number of subjects analysed	10	10	4
Units: Percentage of subjects
arithmetic mean (confidence interval 80%)	50.0 (26.73 to 73.27)	70.0 (44.83 to 88.42)	50.0 (14.26 to 85.74)

No statistical analyses for this end point

Secondary: Panel 1, 2 and 3: Percentage of Subjects Who Achieved HBeAg Seroclearance

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End point title

Panel 1, 2 and 3: Percentage of Subjects Who Achieved HBeAg Seroclearance

End point description

Percentage of subjects who achieved HBeAg Seroclearance were reported. HBeAg seroclearance was defined as (quantitative) HBeAg <LLOQ (<0.11 IU/mL). ITT population included subjects who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Subjects were analyzed according to study intervention they were randomly assigned or enrolled. Here "N" (Number of subjects analyzed) signifies the number of subjects that were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Follow-up Week 48

End point values	Follow-up Phase: Panel 1	Follow-up Phase: Panel 2	Follow-up Phase: Panel 3
Number of subjects analysed	10	10	4
Units: percentage of Subjects
number (not applicable)	25.0	20.0	0

No statistical analyses for this end point

Secondary: Panel 1, 2 and 3: Percentage of Subjects With Sustained (Reduction) Serum HBsAg Response Per Definition 2 at Follow-up Week 48

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End point title

Panel 1, 2 and 3: Percentage of Subjects With Sustained (Reduction) Serum HBsAg Response Per Definition 2 at Follow-up Week 48

End point description

Percentage of subjects with sustained (reduction) serum HBsAg response per Definition 2 at follow-up Week 48 were reported. Sustained serum HBsAg response per definition 2 was defined as: for subjects with a >1 log decline in HBsAg from baseline at last follow up visit: Among the most recent three visits, the difference between log HBsAg at 2 of 3 last visit and 1 of 3 last visit is <0.2, and the difference between log HBsAg at 3 of 3 last visit and 1 of 3 last visit is <0.2. ITT population included subjects who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Subjects were analyzed according to study intervention they were randomly assigned or enrolled. Here "N" (Number of subjects analyzed) signifies the number of subjects that were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Follow-up Week 48

End point values	Follow-up Phase: Panel 1	Follow-up Phase: Panel 2	Follow-up Phase: Panel 3
Number of subjects analysed	8	7	2
Units: Percentage of subjects
arithmetic mean (confidence interval 80%)	50.0 (23.97 to 76.03)	42.9 (16.96 to 72.14)	50.0 (5.13 to 94.87)

No statistical analyses for this end point

Secondary: Panel 1, 2 and 3: Percentage of SubjectsWith Sustained (Reduction) Serum HBsAg Response Per Definition 4 at Follow-up Week 48

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End point title

Panel 1, 2 and 3: Percentage of SubjectsWith Sustained (Reduction) Serum HBsAg Response Per Definition 4 at Follow-up Week 48

End point description

Percentage of subjects with sustained (reduction) serum HBsAg response per definition 4 follow-up Week 48 were reported. Sustained serum HBsAg response per definition 4 were classified into 3 categories with respect to the difference between HBsAg level at the last Follow-up timepoint and end of treatment: Increase: >+0.2 log10 IU/mL , stable: within plus or minus (+/-) 0.2 log10 IU/mL, and decrease: >-0.2 log10 IU/mL. ITT population included subjects who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Subjects were analyzed according to study intervention they were randomly assigned or enrolled. Here "N" (Number of subjects analyzed) signifies the number of subjects that were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Follow-up Week 48

End point values	Follow-up Phase: Panel 1	Follow-up Phase: Panel 2	Follow-up Phase: Panel 3
Number of subjects analysed	9	10	4
Units: Percentage of subjects
number (not applicable)
Stable: Within +/-0.2 log10	11.1	0	0
Decrease: > -0.2 log10 IU/mL	22.2	30.0	25.0
Increase: > +0.2 log10 IU/mL	66.7	70.0	75.0

No statistical analyses for this end point

Secondary: Panel 1, 2 and 3: Percentage of Subjects With Sustained (Reduction) Serum HBsAg Response Per Definition 3 at Follow-up Week 48

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End point title

Panel 1, 2 and 3: Percentage of Subjects With Sustained (Reduction) Serum HBsAg Response Per Definition 3 at Follow-up Week 48

End point description

Percentage of subjects with sustained (reduction) serum HBsAg response per Definition 3 at follow-up Week 48 were reported. Sustained serum HBsAg response per definition 3 for subjects with a >1 log decline in HBsAg from baseline at last follow up visit: Among the most recent three visits, the difference between log HBsAg at 2 of 3 last visit and 1 of 3 last visit is <0.2, and the difference between log HBsAg at 3 of 3 last visit and 1 of 3 last visit is <0.2 and have an HBsAg <1000 IU/mL at the last available timepoint. ITT population included subjects who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Subjects were analyzed according to study intervention they were randomly assigned or enrolled. Here "N" (Number of subjects analyzed) signifies the number of subjects that were evaluable for this endpoint.

End point type

Secondary

End point timeframe

From follow-up Week 24 up to follow-up Week 48

End point values	Follow-up Phase: Panel 1	Follow-up Phase: Panel 2	Follow-up Phase: Panel 3
Number of subjects analysed	8	7	2
Units: Percentage of subjects
number (confidence interval 80%)	25.0 (6.86 to 53.82)	42.9 (16.96 to 72.14)	50.0 (5.13 to 94.8)

No statistical analyses for this end point

Secondary: Panel 1, 2 and 3: Percentage of Subjects Who Achieved HBsAg Seroconversion

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End point title

Panel 1, 2 and 3: Percentage of Subjects Who Achieved HBsAg Seroconversion

End point description

Seroconversion of HBsAg was defined as having achieved HBsAg seroclearance (defined as quantitative HBsAg <LLOQ [<0.05 IU/mL]) and appearance of anti-HBs antibodies (defined as a baseline anti-HBs antibodies [quantitative] <LLOQ [<5 milli-international units per milliliter {mIU/mL}] and a post-baseline assessment >=LLOQ [>=5 mIU/mL]). ITT population included subjects who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Subjects were analyzed according to study intervention they were randomly assigned or enrolled. Here, 'N' (number of subjects analyzed) signifies number of subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

From baseline (Day 1) up to follow-up Week 48

End point values	OL Phase: Panel 1	OL Phase: Panel 2	OL Phase: Panel 3
Number of subjects analysed	8	7	2
Units: Percentage of subjects
number (not applicable)	28.6	11.1	0

No statistical analyses for this end point

Secondary: Panel 1, 2 and 3: Percentage of Subjects who Achieved HBeAg Seroclearance

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End point title

Panel 1, 2 and 3: Percentage of Subjects who Achieved HBeAg Seroclearance

End point description

End point type

Secondary

End point timeframe

Follow-up Week 48

End point values	Follow-up Phase: Panel 1	Follow-up Phase: Panel 2	Follow-up Phase: Panel 3
Number of subjects analysed	8	9	4
Units: percentage of subjects
number (not applicable)	37.5	100.0	75.0

No statistical analyses for this end point

Secondary: Panel 1, 2 and 3: Percentage of Subjects who Achieved HBeAg Seroconversion

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End point title

Panel 1, 2 and 3: Percentage of Subjects who Achieved HBeAg Seroconversion

End point description

Percentage of subjects who achieved HBeAg seroconversion were reported. Seroconversion of HBeAg was defined as having achieved HBeAg seroclearance (defined as [quantitative] HBeAg <LLOQ [<0.11 IU/mL]) together with appearance of anti-HBe antibodies (defined as a baseline anti-HBe antibodies [qualitative] with a "negative" result and a post-baseline assessment with “positive” result). ITT population included subjects who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Subjects were analyzed according to study intervention they were randomly assigned or enrolled. Here "N" (Number of subjects analyzed) signifies the number of subjects that were evaluable for this endpoint. Here 99999 signifies that no subject was available for the analysis.

End point type

Secondary

End point timeframe

From baseline (Day 1) up to follow-up Week 48

End point values	OL Phase: Panel 1	OL Phase: Panel 2	OL Phase: Panel 3
Number of subjects analysed	7	0 ^[20]	2
Units: Percentage of subjects
number (not applicable)	28.6		50.0

Notes
[20] - Here N=0 signifies that data were not collected and analyzed for this arm.

No statistical analyses for this end point

Secondary: Panel 1, 2 and 3: Percentage of Subjects With Off-treatment Virologic Flares per Derivation 1

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End point title

Panel 1, 2 and 3: Percentage of Subjects With Off-treatment Virologic Flares per Derivation 1

End point description

Virologic flare (VF) per derivation 1 was defined only for subjects who were off-treatment [OFT: period after stopping all study drugs, including NA] and who had HBV DNA<LLOQ (<20 IU/mL) at last observed point on-treatment [OT]); start date [SD] of confirmed VF was first date of 2 consecutive visits with HBV DNA >200 IU/mL. End date [ED] of same confirmed VF was first date when HBV DNA value returns to <=200 IU/mL or date of NA restart, whichever comes first. Each virologic flare were categorized based on confirmed (that is, 2 consecutive values) peak HBV DNA above any of 3 thresholds within the start and end date of that flare as followed: 20,000 IU/mL, 2,000 IU/mL, and 200 IU/mL. Subjects were counted only once for any given flare, regardless of the number of times they actually experienced the flare. ITT set were analysed. Here "N" (Subjects analysed) signifies subjects evaluable for this endpoint. 99999 signifies that no subjects were available for the analysis.

End point type

Secondary

End point timeframe

From baseline (Day 1) up to follow-up Week 48

End point values	OL Phase: Panel 1	OL Phase: Panel 2	OL Phase: Panel 3
Number of subjects analysed	0 ^[21]	3	2
Units: percentage of subjects
number (not applicable)
HBV DNA > 200 IU/mL		0	0
HBV DNA > 2,000 IU/mL		33.3	0
HBV DNA > 20,000 IU/mL		0	50.0

Notes
[21] - N=0 signifies that data were not collected and analyzed for this arm.

No statistical analyses for this end point

Secondary: Panel 1, 2 and 3: Percentage of Subjects With Off-treatment and On-treatment Biochemical Flares

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End point title

Panel 1, 2 and 3: Percentage of Subjects With Off-treatment and On-treatment Biochemical Flares

End point description

Off-treatment biochemical flare was defined as first date of 2 consecutive visits with ALT and/or AST >=3*ULN and >=3*nadir while subject received no study drugs. End date of same off-treatment biochemical flare =first date with 50 % reduction from peak ALT and/or AST level & <3*ULN. On-treatment (time period during which the subject received any of study drugs) biochemical flare =first date of 2 consecutive visits with ALT and/ or AST >=3*ULN and >=3*nadir (lowest value observed up to start of flare) while subject was on-treatment. End date of same on-treatment biochemical flare =first date with a 50% reduction from the peak ALT and/or AST level and <3*ULN, regardless of stopping study drugs. Subjects were counted only once for any given flare, regardless of the number of times they actually experienced flare. ITT Population. Here, "n"=number of subjects analyzed at specified categories and 99999 signifies that no subject was available for the analysis at the specified category.

End point type

Secondary

End point timeframe

From baseline (Day 1) up to follow-up Week 48

End point values	Panel 1	Panel 2	Panel 3
Number of subjects analysed	10	10	10
Units: Percentage of subjects
number (not applicable)
Off-treatment biochemical flare (n=0, 3, 2)	99999	0	0
On-treatment biochemical flare (n=10, 10, 4)	10.0	10.0	25.0

No statistical analyses for this end point

Secondary: Panel 1, 2 and 3: Percentage of Subjects With Off-treatment Clinical Flares

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End point title

Panel 1, 2 and 3: Percentage of Subjects With Off-treatment Clinical Flares

End point description

Clinical flares occurred either when a virologic flare and biochemical flare overlapped in time or when a biochemical flare started within 4 weeks following the end of a virologic flare. Off-treatment was defined as the time period after stopping all study drugs (including NA). The start date of a clinical flare was the minimum start date of the virologic flare and biochemical flare. The end date of a clinical flare was the maximum end date of the virologic flare and biochemical flare, that is, the later date between HBV DNA returned to <=200 IU/mL (or <=1 log10) and 50 %reduction from the peak ALT and/or AST level and <3*ULN reached during the biochemical flare. Subjects were counted only once for any given flare, regardless of the number of times they actually experienced the flare. ITT Population. Here, "n"=number of subjects analyzed at specified categories and 99999 signifies that no subject was available for the analysis at the specified category.

End point type

Secondary

End point timeframe

From baseline (Day 1) up to follow-up Week 48

End point values	Panel 1	Panel 2	Panel 3
Number of subjects analysed	0 ^[22]	3	2
Units: percentage of subjects
number (not applicable)
HBV DNA >200 IU/mL (n=0, 3, 2)		0	0
HBV DNA >2,000 IU/mL (n=0, 3, 2)		0	0
HBV DNA >20,000 IU/mL (n=0, 3, 2)		0	50.0

Notes
[22] - N=0 signifies that no subjects were available for the analysis.

No statistical analyses for this end point

Secondary: Panel 1, 2 and 3: Time to Achieve First HBsAg Seroclearance

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End point title

Panel 1, 2 and 3: Time to Achieve First HBsAg Seroclearance

End point description

Time to first occurrence of HBsAg seroclearance (defined as quantitative HBsAg <LLOQ [<0.05 IU/mL]) were reported. Time to first occurrence of HBsAg seroclearance was defined as the number of days between the date of first study intervention intake and the date of the first occurrence of the HBsAg seroclearance. Subjects who withdrew early from the study before achieving HBsAg seroclearance or who did not achieve HBsAg seroclearance were censored at the last available HBsAg assessment. Kaplan-Meier method was used for estimation. ITT population included subjects who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Subjects were analyzed according to study intervention they were randomly assigned or enrolled. Here, 99999 signifies that median and 80% CI data were not estimable due to insufficient number of subjects with events.

End point type

Secondary

End point timeframe

From baseline (Day 1) up to follow-up Week 48

End point values	OL Phase: Panel 1	OL Phase: Panel 2	OL Phase: Panel 3
Number of subjects analysed	10	10	4
Units: weeks
median (full range (min-max))	99999 (99999 to 99999)	99999 (99999 to 99999)	99999 (99999 to 99999)

No statistical analyses for this end point

Secondary: Panel 1, 2 and 3: Percentage of Subjects With Virologic Breakthrough

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End point title

Panel 1, 2 and 3: Percentage of Subjects With Virologic Breakthrough

End point description

Virological breakthrough was defined as having a confirmed on-treatment HBV DNA increase by >1 log10 IU/mL from nadir level (lowest level reached during treatment) in subjects who did not have on-treatment HBV DNA level < LLOQ (<20 IU/mL) or confirmed on-treatment HBV DNA level >200 IU/mL in subjects who had on-treatment HBV DNA level <LLOQ (<20 IU/mL) of the HBV DNA assay. Confirmed HBV DNA increase/level means that the criterion should be fulfilled at 2 or more consecutive time points or at the last observed on-treatment time point. On treatment was defined as the time period in which the subject received any of the study interventions (JNJ-3989 and/or JNJ 6379 and/or NA and/or PegIFN-alpha2a). ITT population included subjects who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Subjects were analyzed according to study intervention they were randomly assigned or enrolled.

End point type

Secondary

End point timeframe

From baseline (Day 1) up to follow-up Week 48

End point values	OL Phase: Panel 1	OL Phase: Panel 2	OL Phase: Panel 3
Number of subjects analysed	10	10	4
Units: Percentage of subjects
number (confidence interval 80%)	0 (0.00 to 20.57)	0 (0.00 to 20.57)	0 (0.00 to 43.77)

No statistical analyses for this end point

Secondary: Panel 1, 2 and 3: Number of Subjects With HBV-Specific Peripheral Blood T-cell Responses

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End point title

Panel 1, 2 and 3: Number of Subjects With HBV-Specific Peripheral Blood T-cell Responses

End point description

Number of subjects with HBV-specific peripheral blood T-cell responses were reported. HBV-specific T-cells were characterized in peripheral blood mononuclear cell immune analysis by binding assays (multimer staining) combined with downstream T-cell responses and transcriptome profiling. ITT population included subjects who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Here "N" (Number of subjects analyzed) signifies the number of subjects that were evaluable for this endpoint and "n"=number of subjects analyzed at specified categories and 99999 signifies that no subject was available for the analysis at the specified category.

End point type

Secondary

End point timeframe

Open-label phase: Weeks 40, 44, and 48; Follow-up Phase: Follow-up Weeks 2, 12 and 24

End point values	OL Phase: Panel 1	Follow-up Phase: Panel 1	OL Phase: Panel 2	Follow-up Phase: Panel 2	OL Phase: Panel 3	Follow-up Phase: Panel 3
Number of subjects analysed	7	9	7	10	1	4
Units: Subjects
Open Label: Week 40 (n= 7, 7, 1, 0, 0, 0)	6	0	6	0	0	0
Open Label: Week 44 (n= 1, 1,0, 0, 0, 0)	0	0	1	0	99999	0
Open Label: Week 48 (n=1, 0, 0, 0, 0, 0)	1	0	99999	0	99999	0
Follow-up Week 2 (n=0, 0, 0, 8, 10, 3)	0	4	0	10	0	3
Follow-up Week 12 (n= 0, 0, 0, 8, 10, 3 )	0	1	0	5	0	2
Follow-up Week 24 (n= 0, 0, 0, 9, 9, 4)	0	5	0	9	0	4

No statistical analyses for this end point

Secondary: Panel 1, 2 and 3: Percentage of Subjects With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

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End point title

Panel 1, 2 and 3: Percentage of Subjects With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

End point description

Percentage of subjects with TEAES (including serious and non-serious) and TESAEs were reported. An AE was any untoward medical occurrence in a clinical study subject administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Any AE occurring at or after the initial administration of study intervention was considered to be treatment emergent. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/ incapacity; congenital anomaly. Safety analysis set included all subjectswho received at least 1 dose of study intervention. Subjects were analyzed according to the study intervention they actually received.

End point type

Secondary

End point timeframe

Open-label: Day 1 (Week 0) up to Week 48; Follow-up Phase: Follow-up Week 1 up to follow-up Week 48

End point values	OL Phase: Panel 1	Follow-up Phase: Panel 1	OL Phase: Panel 2	Follow-up Phase: Panel 2	OL Phase: Panel 3	Follow-up Phase: Panel 3
Number of subjects analysed	10	10	10	10	4	4
Units: Percentage of subjects
number (not applicable)
TEAES	90.0	50.0	100.0	60.0	75.0	75.0
TESAES	10.0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Panel 1, 2 and 3: Percentage of Subjects With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests

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End point title

Panel 1, 2 and 3: Percentage of Subjects With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests

End point description

Clinical laboratory test parameters were Hematology : absolute neutrophil count (ANC); Chemistry : alanine aminotransferase (ALT) and serum glutamic pyruvic transaminase (SGPT), aspartate aminotransferase(AST) or serum glutamic oxaloacetic transaminase (SGOT), amylase (pancreatic and total), creatinine Kinase, creatinine, low-density lipoprotein (LDL), lipase, estimated glomerular filtration rate (eGFR) on serum creatinine (Cr). DAIDS toxicity grades (Gd) were Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe), Grade 4 (Potentially Life-Threatening). Percentage of subjects with treatment-emergent DAIDS toxicity Grade 3 or 4 were reported in this endpoint. For toxicity grades, treatment-emergent was concluded if the postbaseline grade was worse than the baseline grade. Only those abnormality with at least one subject were reported. Safety analysis set. Subjects were analyzed as per study intervention they actually received. "n"=number of subjects analyzed at specified categories.

End point type

Secondary

End point timeframe

Open-label phase: From Day 1 (Week 0) up to Week 48; Follow-up Phase: Follow-up Week 1 up to follow-up Week 48

End point values	OL Phase: Panel 1	Follow-up Phase: Panel 1	OL Phase: Panel 2	Follow-up Phase: Panel 2	OL Phase: Panel 3	Follow-up Phase: Panel 3
Number of subjects analysed	10	10	10	10	4	4
Units: Percentage of subjects
number (not applicable)
Hem: ANC: Low: Grade 3 (n=9, 10, 4, 10, 10, 4)	0	0	10.0	10.0	25.0	25.0
ALT or SGPT: High: Gd 3 (n= 9, 10, 4, 10, 10, 4)	0	10.0	10.0	10.0	25.0	0
ALT or SGPT: High: Gd 4 (n=9, 10, 4, 10, 10,4)	0	0	0	0	0	25.0
AST/SGOT: High: Gd 3 (n=9,10,4,10,10,4)	0	0	10.0	0	0	25.0
Amylase (Pancreatic): High: Gd 4 (n=4,5,4,4,5,3)	25.0	0	0	0	0	0
Amylase (Total): High:Grade 3 (n=9,10,4,9,10,4)	11.1	0	0	0	0	0
Creatinine Kinase-High: Gd 3 (n=9,10,4,10,10,4)	0	0	0	0	25.0	0
Creatinine Kinase :High: Gd 4 (n=9,10,4,10,10,4)	0	0	10.0	0	0	0
Creatinine: High: Gd 3 (n=9, 10, 4, 10, 10, 4)	11.1	0	0	0	0	0
LDL (Fasting):High: Gd 3 (n=9,10,4,10,10,4)	0	0	10.0	0	0	0
Lipase: High: Gd 3 (n=9, 10, 4, 9, 10, 4)	0	0	10.0	0	0	0
eGFR Cr: Low: Gd 3 (n=9, 10, 4 10, 10, 4)	0	0	10.0	0	0	0

No statistical analyses for this end point

Secondary: Panel 1, 2 and 3: Percentage of Subjects With Worst (Abnormally Low/High)Treatment-emergent DAIDS Toxicity Grade in Electrocardiogram (ECG)

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End point title

Panel 1, 2 and 3: Percentage of Subjects With Worst (Abnormally Low/High)Treatment-emergent DAIDS Toxicity Grade in Electrocardiogram (ECG)

End point description

ECG parameters included ECG mean heart rate (HR)(beats per minute[bpm]), Pulse rate (PR) interval (milliseconds [ms]), QRS duration (ms) and QTc Corrected (Fridericia’s formula QTcF). Abnormalities were graded as follows: ECG mean heart rate (abnormally low HR <45 bpm) and (abnormally high HR>=120 bpm); PR interval (abnormally high >220 ms) and QPRS (abnormally high >=120 ms); OT interval corrected for heart rate according to Fridericia (QTcF); borderline prolonged (BRD Pr )QTc (>=450 to <=480 ms), prolonged QTc (>=480 to <=500 ms)and pathologically prolonged QTc (>500 ms). For worst abnormality, treatment-emergent was concluded if the abnormality worsened as compared to the abnormality at baseline: abnormally high to abnormally low and vice-versa. Only those abnormality with at least one subject had data were reported. Safety analysis set. Subjects were analyzed as per study intervention they actually received. "n"=number of subjects analyzed at specified categories.

End point type

Secondary

End point timeframe

Open-label phase: From Day 1 (Week 0) up to Week 48; Follow-up Phase: Follow-up Week 1 up to follow-up Week 48

End point values	OL Phase: Panel 1	Follow-up Phase: Panel 1	OL Phase: Panel 2	Follow-up Phase: Panel 2	OL Phase: Panel 3	Follow-up Phase: Panel 3
Number of subjects analysed	9	9	10	10	4	4
Units: Percentage of subjects
number (not applicable)
ECG Mean HR: low (<45 bpm) (n=9, 10, 4, 9, 10, 4)	0	0	10.0	10.0	0	0
PR:Aggregate(Agg):High:>220 ms:(n=9,10,4,9,10,4)	11.1	11.1	20.0	20.0	0	0
QTcF:Agg:BRD Pr:>=450to<=480 ms:(n=9,10,4,9,10,4)	0	0	10.0	0	0	0

No statistical analyses for this end point

Secondary: Panel 1, 2 and 3: Percentage of Subjects With Worst (Abnormally Low/High) Treatment-emergent DAIDS Toxicity Grade in Vital Signs

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End point title

Panel 1, 2 and 3: Percentage of Subjects With Worst (Abnormally Low/High) Treatment-emergent DAIDS Toxicity Grade in Vital Signs

End point description

Percentage of subjects with worst treatment-emergent DAIDS toxicity grade in vital signs were reported. Abnormality grades were: pulse rate (abnormally low <=45 bpm) and (abnormally high >=120 bpm). An assessment was treatment-emergent if abnormality worsened as compared to the abnormality at baseline: from abnormally high to abnormally low and vice-versa. Only the category (pulse rate) in which at least one subject had data were reported. Safety analysis set included all subjects who received at least 1 dose of study intervention. Subjects were analyzed according to the study intervention they actually received. Here "N" (Number of subjects analyzed) signifies subjects who were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Open-label phase: From Day 1 (Week 0) up to Week 48; Follow-up Phase: Follow-up Week 1 up to follow-up Week 48

End point values	OL Phase: Panel 1	Follow-up Phase: Panel 1	OL Phase: Panel 2	Follow-up Phase: Panel 2	OL Phase: Panel 3	Follow-up Phase: Panel 3
Number of subjects analysed	9	10	10	10	4	4
Units: Percentage of subjects
number (not applicable)	0	0	10.0	0	0	0

No statistical analyses for this end point

Secondary: Panel 1, 2 and 3: Number of Subjects With Clinically Significant Treatment-emergent Abnormalities in Physical Examination

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End point title

Panel 1, 2 and 3: Number of Subjects With Clinically Significant Treatment-emergent Abnormalities in Physical Examination

End point description

Number of subjects with clinically significant treatment-emergent abnormalities in physical examination were reported. Physical examination included head/neck/thyroid, eyes/ears/nose/throat, respiratory, cardiovascular, lymph nodes, abdomen, skin, musculoskeletal, and neurological examinations. Safety analysis set included all subjects who received at least 1 dose of study intervention. Subjects were analyzed according to the study intervention they actually received.

End point type

Secondary

End point timeframe

Open-label phase: From Day 1 (Week 0) up to Week 48; Follow-up Phase: Follow-up Week 1 up to follow-up Week 48

End point values	OL Phase: Panel 1	Follow-up Phase: Panel 1	OL Phase: Panel 2	Follow-up Phase: Panel 2	OL Phase: Panel 3	Follow-up Phase: Panel 3
Number of subjects analysed	10	10	10	10	4	4
Units: Subjects	4	0	0	0	0	0

No statistical analyses for this end point

Secondary: Panel 2 and 3: Plasma Trough Concentration (C[0hour]) of JNJ-73763989 (JNJ-73763976, JNJ-73763924)

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End point title

Panel 2 and 3: Plasma Trough Concentration (C[0hour]) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) ^[23]

End point description

Plasma trough concentration (C[0hour]) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) were reported. C0h was the pre-dose plasma concentration of the JNJ-73763989 (JNJ-73763976, JNJ-73763924). Non-compartmental analysis were conducted to analyze plasma concentration of JNJ-73763989 and its molecules. Pharmacokinetics (PK) analysis which included subjects of Panel 2 and Panel 3 who had consented to participate in the intensive PK subgroup were analyzed. Data for this endpoint was planned to be collected and analyzed for Panel 2 and 3 alone. Here, "99999" signifies that mean and standard deviation were not calculable because sample concentration was below quantification limit (that is <2.1 ng/mL)..

End point type

Secondary

End point timeframe

Week 4 : Pre-dose on Day 29

Notes
[23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Data for this endpoint was planned to be collected and analyzed for Panel 2 and 3 alone.

End point values	OL Phase: Panel 2	OL Phase: Panel 3
Number of subjects analysed	3	4
Units: nanograms per milliliter (ng/mL)
arithmetic mean (standard deviation)
C0hJNJ-73763976	99999 ( 99999 )	99999 ( 99999 )
C0h-JNJ-73763924	99999 ( 99999 )	99999 ( 99999 )

No statistical analyses for this end point

Secondary: Panel 2 and 3: Maximum Observed Plasma Concentration (Cmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924)

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End point title

Panel 2 and 3: Maximum Observed Plasma Concentration (Cmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) ^[24]

End point description

Maximum observed plasma concentration (Cmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) were reported. Non-compartmental analysis were conducted to analyze Cmax JNJ-73763989 and its molecules. A PK analysis which included subjects of Panel 2 and Panel 3 who had consented to participate in the intensive PK subgroup were analyzed. Data for this endpoint was planned to be collected and analyzed for Panel 2 and 3 alone. Here, "99999" signifies that data were not collected and analyzed when the subjects available for analysis were less than 3 as planned .

End point type

Secondary

End point timeframe

Week 4 (Day 29): Pre-dose and 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose

Notes
[24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Data for this endpoint was planned to be collected and analyzed for Panel 2 and 3 alone.

End point values	OL Phase: Panel 2	OL Phase: Panel 3
Number of subjects analysed	0 ^[25]	4
Units: Nanograms per milliliter (ng/mL)
arithmetic mean (standard deviation)
Cmax: JNJ-73763976	( )	924 ( 428 )
Cmax: JNJ-73763924	( )	178 ( 73.1 )

Notes
[25] - N=0 signifies data were not calculable because a sufficient number of subjects were not available.

No statistical analyses for this end point

Secondary: Panel 2 and 3: Minimum Observed Plasma Concentration (Cmin) of JNJ-73763989 (JNJ-73763976, JNJ-73763924)

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End point title

Panel 2 and 3: Minimum Observed Plasma Concentration (Cmin) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) ^[26]

End point description

Minimum observed plasma concentration (Cmin) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) were reported. Non-compartmental analysis were conducted to analyze Cmin of JNJ-73763989 and its molecules. A PK analysis which included subjects of Panel 2 and Panel 3 who had consented to participate in the intensive PK subgroup were analyzed. Data for this endpoint was planned to be collected and analyzed for Panel 2 and 3 alone. Here, 99999 signifies that mean and standard deviation were not calculable because sample concentration was below quantification limit (that is <2.1 ng/mL).

End point type

Secondary

End point timeframe

Week 4 (Day 29): Pre-dose and 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose

Notes
[26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Data for this endpoint was planned to be collected and analyzed for Panel 2 and 3 alone.

End point values	OL Phase: Panel 2	OL Phase: Panel 3
Number of subjects analysed	3	4
Units: nanograms per milliliter (ng/mL)
arithmetic mean (standard deviation)
Cmin: JNJ-73763976	99999 ( 99999 )	99999 ( 99999 )
Cmin: JNJ-73763924	99999 ( 99999 )	99999 ( 99999 )

No statistical analyses for this end point

Secondary: Panel 2 and 3:Time to Reach the Maximum Observed Plasma Concentration (Tmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924)

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End point title

Panel 2 and 3:Time to Reach the Maximum Observed Plasma Concentration (Tmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) ^[27]

End point description

Time to reach the maximum observed plasma concentration (tmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) were reported. Non-compartmental analysis were conducted to analyze tmax of JNJ-73763989 and its molecules. A PK analysis which included subjects of Panel 2 and Panel 3 who had consented to participate in the intensive PK subgroup were analyzed. Here, 99999, signifies that data were not collected and analyzed when the subjects available for analysis were less than 3 as planned. Data for this endpoint was planned to be collected and analyzed for Panel 2 and 3 alone.

End point type

Secondary

End point timeframe

Week 4 (Day 29): Pre-dose and 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose

Notes
[27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Data for this endpoint was planned to be collected and analyzed for Panel 2 and 3 alone.

End point values	OL Phase: Panel 2	OL Phase: Panel 3
Number of subjects analysed	0 ^[28]	4
Units: hours (h)
median (full range (min-max))
tmax: JNJ-73763976	( to )	6.00 (3.00 to 10.00)
tmax: JNJ-73763924	( to )	5.04 (3.00 to 10.00)

Notes
[28] - N=0 signifies data were not calculable because a sufficient number of subjects were not available.

No statistical analyses for this end point

Secondary: Panel 2 and 3:Area Under the Plasma Concentration-time Curve From Time Zero to 24hours (AUC0 to 24h) of JNJ-73763989 (JNJ-73763976, JNJ-73763924)

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End point title

Panel 2 and 3:Area Under the Plasma Concentration-time Curve From Time Zero to 24hours (AUC0 to 24h) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) ^[29]

End point description

Area under the plasma concentration-time curve from time zero to 24hours (AUC0 to 24h) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) were reported. Non-compartmental analysis were conducted to analyze AUC0 to 24h of JNJ-73763989 and its molecules. A PK analysis which included subjects of Panel 2 and Panel 3 who had consented to participate in the intensive PK subgroup were analyzed. Here, 99999, signifies that data were not collected and analyzed when the subjects available for analysis were less than 3 as planned. Data for this endpoint was planned to be collected and analyzed for Panel 2 and 3 alone.

End point type

Secondary

End point timeframe

Week 4 (Day 29): Pre-dose and 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose

Notes
[29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Data for this endpoint was planned to be collected and analyzed for Panel 2 and 3 alone.

End point values	OL Phase: Panel 2	OL Phase: Panel 3
Number of subjects analysed	0 ^[30]	4
Units: nanogramshour per milliliters (ngh/mL)
arithmetic mean (standard deviation)
AUC0 to 24h:JNJ-73763976	( )	13256 ( 6314 )
AUC0 to 24h: JNJ-73763924	( )	2394 ( 1047 )

Notes
[30] - N=0 signifies data were not calculable because a sufficient number of subjects were not available.

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Open-label phase: From Day 1 (Week 1) up to Week 48; Follow-up Phase: Follow-up Week 1 up to follow-up Week 48

Adverse event reporting additional description

Safety analysis set included all subjects who received at least 1 dose of study intervention. Subjects were analyzed according to the study intervention they actually received.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

26.1

Reporting group title

OL Phase: Panel 1

Reporting group description

Prior to PA 5, subjects received either JNJ-3989 200 milligrams (mg) subcutaneous(SC) injection every 4 weeks(Q4W) from Day 1 (Week 1) to Week 44+JNJ-6379 250 mg once daily(QD)+NA (ETV 0.5 mg/TD 245 mg/TAF 25 mg) QD from Day 1 (Week 1) to Week 48 or JNJ-3989 200 mg SC injection Q4W from Day 1 (Week 1) to Week 44+NA (ETV 0.5 mg/TD 245 mg/TAF 25 mg) QD from Day 1 (Week 1) to Week 48. After PA 5, subjects stopped JNJ-6379 and continued JNJ-3989+NA. With separate consent, subjects received optional treatment: PegIFN-alpha-2a 180 micrograms(mcg) SC injection once weekly(QW) post Week 40 liver biopsy for either 12 or 24 weeks (anytime between study Week 40 to 72) at investigator's discretion. At end of treatment Week 48, all subjects entered FU phase and stopped JNJ-3989/JNJ-6379 and NA, if NA treatment completion criteria was met as per Week 44 laboratory tests. If NA treatment completion criteria were not met at Week 48, NA was continued till FU phase end (study Week 96).

Reporting group title

OL Phase: Panel 2

Reporting group description

Reporting group title

FU Phase: Panel 2

Reporting group description

Reporting group title

FU Phase: Panel 1

Reporting group description

Reporting group title

FU Phase: Panel 3

Reporting group description

Reporting group title

OL Phase: Panel 3

Reporting group description

Serious adverse events	OL Phase: Panel 1	OL Phase: Panel 2	FU Phase: Panel 2	FU Phase: Panel 1	FU Phase: Panel 3	OL Phase: Panel 3
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
number of deaths (all causes)	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0
Infections and infestations
Gastroenteritis
subjects affected / exposed	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	OL Phase: Panel 1	OL Phase: Panel 2	FU Phase: Panel 2	FU Phase: Panel 1	FU Phase: Panel 3	OL Phase: Panel 3
Total subjects affected by non serious adverse events
subjects affected / exposed	9 / 10 (90.00%)	10 / 10 (100.00%)	6 / 10 (60.00%)	5 / 10 (50.00%)	3 / 4 (75.00%)	3 / 4 (75.00%)
General disorders and administration site conditions
Asthenia
subjects affected / exposed	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	2 / 4 (50.00%)	1 / 4 (25.00%)
occurrences all number	1	1	0	0	2	1
Influenza Like Illness
subjects affected / exposed	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0
Fatigue
subjects affected / exposed	2 / 10 (20.00%)	2 / 10 (20.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)
occurrences all number	2	2	1	0	0	1
Chills
subjects affected / exposed	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0
Injection Site Bruising
subjects affected / exposed	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0
Injection Site Reaction
subjects affected / exposed	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0
Injection Site Pain
subjects affected / exposed	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0
Injection Site Erythema
subjects affected / exposed	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	1	0	0	0	0
Pyrexia
subjects affected / exposed	1 / 10 (10.00%)	2 / 10 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)
occurrences all number	1	3	0	0	0	1
Reproductive system and breast disorders
Vaginal Haemorrhage
subjects affected / exposed	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	2	0	0	0	0	0
Nasal Congestion
subjects affected / exposed	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	2	0	0
Oropharyngeal Pain
subjects affected / exposed	2 / 10 (20.00%)	0 / 10 (0.00%)	2 / 10 (20.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	2	0	2	0	0	0
Productive Cough
subjects affected / exposed	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0
Rhinorrhoea
subjects affected / exposed	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0
Psychiatric disorders
Mood Swings
subjects affected / exposed	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0
Insomnia
subjects affected / exposed	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0
Depressed Mood
subjects affected / exposed	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0
Investigations
Alanine Aminotransferase Increased
subjects affected / exposed	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	1	0	0
Amylase Increased
subjects affected / exposed	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	7	0	0	2	0	0
Blood Creatine Phosphokinase Increased
subjects affected / exposed	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0
Body Temperature Increased
subjects affected / exposed	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0
Low Density Lipoprotein Increased
subjects affected / exposed	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0
Glomerular Filtration Rate Decreased
subjects affected / exposed	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0
Weight Decreased
subjects affected / exposed	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0
Injury, poisoning and procedural complications
Procedural Pain
subjects affected / exposed	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0
Cardiac disorders
Angina Pectoris
subjects affected / exposed	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0
Nervous system disorders
Dizziness
subjects affected / exposed	2 / 10 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	2	0	0	0	0	0
Headache
subjects affected / exposed	2 / 10 (20.00%)	3 / 10 (30.00%)	1 / 10 (10.00%)	2 / 10 (20.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)
occurrences all number	2	3	1	2	1	0
Sciatica
subjects affected / exposed	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	2	0	0
Thrombocytopenia
subjects affected / exposed	0 / 10 (0.00%)	2 / 10 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	2	0	0	0	0
Neutropenia
subjects affected / exposed	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)
occurrences all number	0	1	0	0	2	1
Ear and labyrinth disorders
Tinnitus
subjects affected / exposed	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0
Eye disorders
Eye Pruritus
subjects affected / exposed	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0
Gastrointestinal disorders
Abdominal Discomfort
subjects affected / exposed	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0
Abdominal Pain Lower
subjects affected / exposed	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	2 / 10 (20.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	2	0	0
Abdominal Pain
subjects affected / exposed	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	2	0	0	0	0	0
Abdominal Pain Upper
subjects affected / exposed	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	1	0	0
Gastritis
subjects affected / exposed	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0
Diarrhoea
subjects affected / exposed	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	1	0	0
Gastrointestinal Sounds Abnormal
subjects affected / exposed	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0
Nausea
subjects affected / exposed	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	0	0
Lip Blister
subjects affected / exposed	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0
Hypoaesthesia Oral
subjects affected / exposed	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0
Vomiting
subjects affected / exposed	2 / 10 (20.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	4	0	1	0	0	0
Skin and subcutaneous tissue disorders
Eczema
subjects affected / exposed	2 / 10 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	2	0	0	0	0	0
Alopecia
subjects affected / exposed	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0
Pruritus
subjects affected / exposed	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	1	0	0	0	0
Rash Macular
subjects affected / exposed	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0
Rash Maculo-Papular
subjects affected / exposed	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0
Renal and urinary disorders
Renal Tubular Disorder
subjects affected / exposed	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0
Musculoskeletal and connective tissue disorders
Back Pain
subjects affected / exposed	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0
Arthralgia
subjects affected / exposed	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0
Groin Pain
subjects affected / exposed	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	2	0	0	0	0	0
Musculoskeletal Chest Pain
subjects affected / exposed	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0
Musculoskeletal Pain
subjects affected / exposed	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0
Myalgia
subjects affected / exposed	1 / 10 (10.00%)	2 / 10 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	2	0	0	0	0
Neck Pain
subjects affected / exposed	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0
Pain in Extremity
subjects affected / exposed	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0
Infections and infestations
Bronchitis
subjects affected / exposed	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0
Covid-19
subjects affected / exposed	1 / 10 (10.00%)	2 / 10 (20.00%)	2 / 10 (20.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)
occurrences all number	1	2	2	0	0	1
Influenza
subjects affected / exposed	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	2	0	0	0
Nasopharyngitis
subjects affected / exposed	0 / 10 (0.00%)	2 / 10 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	2	0	0	0	0
Root Canal Infection
subjects affected / exposed	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0
Tinea Versicolour
subjects affected / exposed	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0
Upper Respiratory Tract Infection
subjects affected / exposed	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	1	0	0
Urinary Tract Infection
subjects affected / exposed	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0
Metabolism and nutrition disorders
Decreased Appetite
subjects affected / exposed	0 / 10 (0.00%)	2 / 10 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	2	0	0	0	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

01 Oct 2021

The primary reasons for this amendment was to remove JNJ-6379 as study intervention, to add a new nucleos(t)ide analog (NA) re-treatment criterion for subjects who discontinued NA treatment during follow-up, and to include more frequent monitoring for subjects who discontinued NA treatment during follow-up.

25 Nov 2021

The primary purpose of this protocol amendmentwas to update the criteria for post-treatment monitoring and for nucleos(t)ide analog (NA) re-treatment for subjects who discontinued NA treatment at Week 48.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Panel 1 and 2: Absolute Change From Baseline in the Percentage of Hepatitis B Surface Antigen (HBsAg) Hepatocytes at Week 40

Primary: Panel 1 and 2: Absolute Change From Baseline in the Percentage of Hepatitis B Surface Antigen (HBsAg) Hepatocytes at Week 40

Primary: Panel 3: Liver Concentrations of JNJ-73763989 (JNJ-73763976, JNJ-73763924 and M65; Deaminated Metabolite of JNJ-73763976) at Week 12

Primary: Panel 3: Liver Concentrations of JNJ-73763989 (JNJ-73763976, JNJ-73763924 and M65; Deaminated Metabolite of JNJ-73763976) at Week 12

Primary: Panel 3: Liver Concentrations of JNJ-73763989 (JNJ-73763976, JNJ-73763924 and M65; Deaminated Metabolite of JNJ-73763976) at Week 40

Primary: Panel 3: Liver Concentrations of JNJ-73763989 (JNJ-73763976, JNJ-73763924 and M65; Deaminated Metabolite of JNJ-73763976) at Week 40

Primary: Panel 3: Plasma Concentration of JNJ-73763989 (JNJ-73763976, JNJ-73763924 and M65; Deaminated Metabolite of JNJ-73763976) at Week 12

Primary: Panel 3: Plasma Concentration of JNJ-73763989 (JNJ-73763976, JNJ-73763924 and M65; Deaminated Metabolite of JNJ-73763976) at Week 12

Primary: Panel 3: Plasma Concentrations of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) at Week 40

Primary: Panel 3: Plasma Concentrations of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) at Week 40

Primary: Panel 3: Correlation of Liver Concentration to Plasma Concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) and Liver Concentration of M65 (Deaminated Metabolite of JNJ-73763976) to Liver Concentration JNJ-73763976 at Week 12

Primary: Panel 3: Correlation of Liver Concentration to Plasma Concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) and Liver Concentration of M65 (Deaminated Metabolite of JNJ-73763976) to Liver Concentration JNJ-73763976 at Week 12

Primary: Panel 3: Correlation of Liver to Plasma Concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) and Liver Concentration of M65 (Deaminated Metabolite of JNJ-73763976) to Liver Concentration JNJ-73763976 at Week 40

Primary: Panel 3: Correlation of Liver to Plasma Concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) and Liver Concentration of M65 (Deaminated Metabolite of JNJ-73763976) to Liver Concentration JNJ-73763976 at Week 40

Secondary: Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Hepatitis B Core Antigen Positive (HBcAg+) Hepatocytes at Week 40

Secondary: Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Hepatitis B Core Antigen Positive (HBcAg+) Hepatocytes at Week 40

Secondary: Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Covalently Closed Circular Deoxyribonucleic Acid Positive (cccDNA+) Hepatocytes at Week 40

Secondary: Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Covalently Closed Circular Deoxyribonucleic Acid Positive (cccDNA+) Hepatocytes at Week 40

Secondary: Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: HBsAg Positive (HBsAg+) Hepatocytes at Week 40

Secondary: Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: HBsAg Positive (HBsAg+) Hepatocytes at Week 40

Secondary: Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Pre-genomic Ribonucleic Acid Positive (pgRNA+) Hepatocytes at Week 40

Secondary: Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Pre-genomic Ribonucleic Acid Positive (pgRNA+) Hepatocytes at Week 40

Secondary: Panel 1 and 2: Change From Baseline in Transcriptional Activity (Ratio of pg RNA/cccDNA) at Week 40

Secondary: Panel 1 and 2: Change From Baseline in Transcriptional Activity (Ratio of pg RNA/cccDNA) at Week 40

Secondary: Panel 1, 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Silent Infected Hepatocytes at Week 40

Secondary: Panel 1, 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Silent Infected Hepatocytes at Week 40

Secondary: Panel 1, 2 and 3: Percentage of Subjects With HBsAg Seroclearance at Week 72 Without Restarting Nucleos(t)Ide Analog (NA) Treatment

Secondary: Panel 1, 2 and 3: Percentage of Subjects With HBsAg Seroclearance at Week 72 Without Restarting Nucleos(t)Ide Analog (NA) Treatment

Secondary: Panel 1, 2 and 3: Percentage of Subjects With Sustained (Reduction) Serum HBsAg Response Per Definition 1 at Follow-up Week 48

Secondary: Panel 1, 2 and 3: Percentage of Subjects With Sustained (Reduction) Serum HBsAg Response Per Definition 1 at Follow-up Week 48

Secondary: Panel 1, 2 and 3: Percentage of Subjects Who Achieved HBeAg Seroclearance

Secondary: Panel 1, 2 and 3: Percentage of Subjects Who Achieved HBeAg Seroclearance

Secondary: Panel 1, 2 and 3: Percentage of Subjects With Sustained (Reduction) Serum HBsAg Response Per Definition 2 at Follow-up Week 48

Secondary: Panel 1, 2 and 3: Percentage of Subjects With Sustained (Reduction) Serum HBsAg Response Per Definition 2 at Follow-up Week 48

Secondary: Panel 1, 2 and 3: Percentage of SubjectsWith Sustained (Reduction) Serum HBsAg Response Per Definition 4 at Follow-up Week 48

Secondary: Panel 1, 2 and 3: Percentage of SubjectsWith Sustained (Reduction) Serum HBsAg Response Per Definition 4 at Follow-up Week 48

Secondary: Panel 1, 2 and 3: Percentage of Subjects With Sustained (Reduction) Serum HBsAg Response Per Definition 3 at Follow-up Week 48

Secondary: Panel 1, 2 and 3: Percentage of Subjects With Sustained (Reduction) Serum HBsAg Response Per Definition 3 at Follow-up Week 48

Secondary: Panel 1, 2 and 3: Percentage of Subjects Who Achieved HBsAg Seroconversion

Secondary: Panel 1, 2 and 3: Percentage of Subjects Who Achieved HBsAg Seroconversion

Secondary: Panel 1, 2 and 3: Percentage of Subjects who Achieved HBeAg Seroclearance

Secondary: Panel 1, 2 and 3: Percentage of Subjects who Achieved HBeAg Seroclearance

Secondary: Panel 1, 2 and 3: Percentage of Subjects who Achieved HBeAg Seroconversion

Secondary: Panel 1, 2 and 3: Percentage of Subjects who Achieved HBeAg Seroconversion

Secondary: Panel 1, 2 and 3: Percentage of Subjects With Off-treatment Virologic Flares per Derivation 1

Secondary: Panel 1, 2 and 3: Percentage of Subjects With Off-treatment Virologic Flares per Derivation 1

Secondary: Panel 1, 2 and 3: Percentage of Subjects With Off-treatment and On-treatment Biochemical Flares

Secondary: Panel 1, 2 and 3: Percentage of Subjects With Off-treatment and On-treatment Biochemical Flares

Secondary: Panel 1, 2 and 3: Percentage of Subjects With Off-treatment Clinical Flares

Secondary: Panel 1, 2 and 3: Percentage of Subjects With Off-treatment Clinical Flares

Secondary: Panel 1, 2 and 3: Time to Achieve First HBsAg Seroclearance

Secondary: Panel 1, 2 and 3: Time to Achieve First HBsAg Seroclearance

Secondary: Panel 1, 2 and 3: Percentage of Subjects With Virologic Breakthrough

Secondary: Panel 1, 2 and 3: Percentage of Subjects With Virologic Breakthrough

Secondary: Panel 1, 2 and 3: Number of Subjects With HBV-Specific Peripheral Blood T-cell Responses

Secondary: Panel 1, 2 and 3: Number of Subjects With HBV-Specific Peripheral Blood T-cell Responses

Secondary: Panel 1, 2 and 3: Percentage of Subjects With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

Secondary: Panel 1, 2 and 3: Percentage of Subjects With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

Secondary: Panel 1, 2 and 3: Percentage of Subjects With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests

Secondary: Panel 1, 2 and 3: Percentage of Subjects With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests

Secondary: Panel 1, 2 and 3: Percentage of Subjects With Worst (Abnormally Low/High)Treatment-emergent DAIDS Toxicity Grade in Electrocardiogram (ECG)

Secondary: Panel 1, 2 and 3: Percentage of Subjects With Worst (Abnormally Low/High)Treatment-emergent DAIDS Toxicity Grade in Electrocardiogram (ECG)

Secondary: Panel 1, 2 and 3: Percentage of Subjects With Worst (Abnormally Low/High) Treatment-emergent DAIDS Toxicity Grade in Vital Signs

Secondary: Panel 1, 2 and 3: Percentage of Subjects With Worst (Abnormally Low/High) Treatment-emergent DAIDS Toxicity Grade in Vital Signs

Secondary: Panel 1, 2 and 3: Number of Subjects With Clinically Significant Treatment-emergent Abnormalities in Physical Examination

Secondary: Panel 1, 2 and 3: Number of Subjects With Clinically Significant Treatment-emergent Abnormalities in Physical Examination

Secondary: Panel 2 and 3: Plasma Trough Concentration (C[0hour]) of JNJ-73763989 (JNJ-73763976, JNJ-73763924)

Secondary: Panel 2 and 3: Plasma Trough Concentration (C[0hour]) of JNJ-73763989 (JNJ-73763976, JNJ-73763924)

Secondary: Panel 2 and 3: Maximum Observed Plasma Concentration (Cmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924)

Secondary: Panel 2 and 3: Maximum Observed Plasma Concentration (Cmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924)

Secondary: Panel 2 and 3: Minimum Observed Plasma Concentration (Cmin) of JNJ-73763989 (JNJ-73763976, JNJ-73763924)