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Clinical Trial Results:
A Phase 2a, Randomized, Partially-blind, Placebo-controlled Study to Assess the Efficacy, Safety, and Pharmacokinetics of Treatment With Multiple Doses of JNJ-56136379 as Monotherapy and in Combination With a Nucleos(t)ide Analog in Subjects With Chronic Hepatitis B Virus Infection

Summary
EudraCT number	2017-001110-29
Trial protocol	GB BE DE ES PL IT
Global end of trial date	13 Aug 2020

Results information
Results version number	v1(current)
This version publication date	29 Aug 2021
First version publication date	29 Aug 2021
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

56136379HPB2001

ISRCTN number

US NCT number

NCT03361956

WHO universal trial number (UTN)

Sponsor organisation name

Janssen-Cilag International NV

Sponsor organisation address

Archimedesweg 29, Leiden, Netherlands, 2333 CM

Public contact

Clinical Registry Group, Janssen-Cilag International NV, ClinicalTrialsEU@its.jnj.com

Scientific contact

Clinical Registry Group, Janssen-Cilag International 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

13 Aug 2020

Is this the analysis of the primary completion data?

Yes

Primary completion date

13 Aug 2020

Global end of trial reached?

Yes

Global end of trial date

13 Aug 2020

Was the trial ended prematurely?

Main objective of the trial

The primary objective was to evaluate efficacy of 24 weeks of study treatment, in terms of changes in hepatitis B surface antigen (HBsAg) levels.

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. Safety evaluations were based upon the type, incidence, and severity of Treatment-emergent adverse events (TEAEs) reported throughout the study, and on changes in physical examination, vital sign measurements, clinical laboratory test results and electrocardiogram (ECG) results.

Background therapy

Evidence for comparator

Actual start date of recruitment

15 Feb 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Belgium: 11

Country: Number of subjects enrolled

Canada: 14

Country: Number of subjects enrolled

China: 18

Country: Number of subjects enrolled

Germany: 9

Country: Number of subjects enrolled

Spain: 12

Country: Number of subjects enrolled

France: 11

Country: Number of subjects enrolled

United Kingdom: 10

Country: Number of subjects enrolled

Hong Kong: 1

Country: Number of subjects enrolled

Italy: 10

Country: Number of subjects enrolled

Japan: 8

Country: Number of subjects enrolled

Korea, Republic of: 7

Country: Number of subjects enrolled

Malaysia: 8

Country: Number of subjects enrolled

Poland: 18

Country: Number of subjects enrolled

Russian Federation: 18

Country: Number of subjects enrolled

Thailand: 7

Country: Number of subjects enrolled

Turkey: 23

Country: Number of subjects enrolled

Taiwan: 32

Country: Number of subjects enrolled

Ukraine: 10

Country: Number of subjects enrolled

United States: 5

Worldwide total number of subjects

232

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)

230

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

A total of 232 subjects were enrolled and 211 completed the study.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

JNJ-56136379- 75 mg (Open label)

Arm description

Subjects currently not treated received 3*25 milligrams (mg) tablets of JNJ-56136379 once daily during the open label phase from Day 1 to Week 24.

Arm type

Experimental

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 75 mg of JNJ-56136379 administered as 3*25 mg of JNJ-56136379 tablets once daily orally during the open-label phase.

Placebo (matching JNJ-6379 75mg) + Nucleos(t)ide analog (NA)

Arm description

Subjects received 3 tablets of matching placebo plus 1 tablet of NA (0.5 mg entecavir [ETV] or 300 mg tenofovir disoproxil fumarate [TDF]) once daily from Day 1 to Week 24.

Arm type

Placebo

Investigational medicinal product name

Nucleos(t)ide analog (NA): ETV or TDF

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received a single tablet of 0.5 mg ETV or 300 mg TDF once daily orally.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received 3 tablets of matching placebo once daily orally.

JNJ-56136379- 75 mg + NA

Arm description

Subjects received 3*25 mg tablets of JNJ-56136379 plus 1 tablet of NA (0.5 mg ETV or 300 mg TDF) once daily from Day 1 to Week 24.

Arm type

Experimental

Investigational medicinal product name

ETV or TDF

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received a single tablet of 0.5 mg ETV or 300 mg TDF once daily orally.

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 75 mg of JNJ-56136379 administered as 3*25 mg of JNJ-56136379 tablets once daily orally.

JNJ-56136379- 250 mg (Open label)

Arm description

Subjects received 2*100 mg and 2*25 mg tablets of JNJ-56136379 once daily during the open-label phase from Day 1 to Week 24.

Arm type

Experimental

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 250 mg of JNJ-56136379 administered as 2*100 mg and 2*25 mg tablets of JNJ-56136379 once daily orally during the open label phase.

Placebo (matching to JNJ-56136379 250 mg) + NA

Arm description

Subjects received 2 tablets of matching placebo plus 1 tablet of NA (0.5 mg ETV or 300 mg TDF) once daily from Day 1 to Week 24.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received 4 tablets of matching placebo (2*100 mg and 2*25 mg) once daily orally.

Investigational medicinal product name

ETV or TDF

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received a single tablet of 0.5 mg ETV or 300 mg TDF once daily orally.

JNJ-56136379- 250 mg + NA

Arm description

Subjects received 2*100 mg and 2*25 mg tablets of JNJ-56136379 plus 1 tablet of NA (0.5 mg ETV or 300 mg TDF) once daily from Day 1 to Week 24.

Arm type

Experimental

Investigational medicinal product name

ETV or TDF

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received a single tablet of 0.5 mg ETV or 300 mg TDF once daily orally.

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 250 mg of JNJ-56136379 administered as 2*100 mg and 2*25 mg tablets of JNJ-56136379 once daily orally.

Number of subjects in period 1	JNJ-56136379- 75 mg (Open label)	Placebo (matching JNJ-6379 75mg) + Nucleos(t)ide analog (NA)	JNJ-56136379- 75 mg + NA	JNJ-56136379- 250 mg (Open label)	Placebo (matching to JNJ-56136379 250 mg) + NA	JNJ-56136379- 250 mg + NA
Started	28	21	66	32	22	63
Completed	24	21	61	28	19	58
Not completed	4	0	5	4	3	5
Physician decision	2	-	-	1	-	-
Adverse event, non-fatal	-	-	1	1	1	-
Other	-	-	-	1	-	-
Lost to follow-up	-	-	1	1	-	2
Withdrawal by subject	2	-	2	-	2	3
Lack of efficacy	-	-	1	-	-	-

Baseline characteristics

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Reporting group title

JNJ-56136379- 75 mg (Open label)

Reporting group description

Subjects currently not treated received 3*25 milligrams (mg) tablets of JNJ-56136379 once daily during the open label phase from Day 1 to Week 24.

Reporting group title

Placebo (matching JNJ-6379 75mg) + Nucleos(t)ide analog (NA)

Reporting group description

Subjects received 3 tablets of matching placebo plus 1 tablet of NA (0.5 mg entecavir [ETV] or 300 mg tenofovir disoproxil fumarate [TDF]) once daily from Day 1 to Week 24.

Reporting group title

JNJ-56136379- 75 mg + NA

Reporting group description

Subjects received 3*25 mg tablets of JNJ-56136379 plus 1 tablet of NA (0.5 mg ETV or 300 mg TDF) once daily from Day 1 to Week 24.

Reporting group title

JNJ-56136379- 250 mg (Open label)

Reporting group description

Subjects received 2*100 mg and 2*25 mg tablets of JNJ-56136379 once daily during the open-label phase from Day 1 to Week 24.

Reporting group title

Placebo (matching to JNJ-56136379 250 mg) + NA

Reporting group description

Subjects received 2 tablets of matching placebo plus 1 tablet of NA (0.5 mg ETV or 300 mg TDF) once daily from Day 1 to Week 24.

Reporting group title

JNJ-56136379- 250 mg + NA

Reporting group description

Subjects received 2*100 mg and 2*25 mg tablets of JNJ-56136379 plus 1 tablet of NA (0.5 mg ETV or 300 mg TDF) once daily from Day 1 to Week 24.

Reporting group values	JNJ-56136379- 75 mg (Open label)	Placebo (matching JNJ-6379 75mg) + Nucleos(t)ide analog (NA)	JNJ-56136379- 75 mg + NA	JNJ-56136379- 250 mg (Open label)	Placebo (matching to JNJ-56136379 250 mg) + NA	JNJ-56136379- 250 mg + NA	Total
Number of subjects	28	21	66	32	22	63	232
Title for AgeCategorical
Units: subjects
Children (2-11 years)	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0
Adults (18-64 years)	27	21	65	32	22	63	230
From 65 to 84 years	1	0	1	0	0	0	2
85 years and over	0	0	0	0	0	0	0
Title for AgeContinuous
Units: years
arithmetic mean (standard deviation)	39.2 ± 12.06	42.5 ± 9.11	40.3 ± 11.12	37.7 ± 10.92	40.8 ± 10.06	40.5 ± 10.99	-
Title for Gender
Units: subjects
Female	9	8	20	14	6	13	70
Male	19	13	46	18	16	50	162

End points

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Reporting group title

JNJ-56136379- 75 mg (Open label)

Reporting group description

Subjects currently not treated received 3*25 milligrams (mg) tablets of JNJ-56136379 once daily during the open label phase from Day 1 to Week 24.

Reporting group title

Placebo (matching JNJ-6379 75mg) + Nucleos(t)ide analog (NA)

Reporting group description

Subjects received 3 tablets of matching placebo plus 1 tablet of NA (0.5 mg entecavir [ETV] or 300 mg tenofovir disoproxil fumarate [TDF]) once daily from Day 1 to Week 24.

Reporting group title

JNJ-56136379- 75 mg + NA

Reporting group description

Subjects received 3*25 mg tablets of JNJ-56136379 plus 1 tablet of NA (0.5 mg ETV or 300 mg TDF) once daily from Day 1 to Week 24.

Reporting group title

JNJ-56136379- 250 mg (Open label)

Reporting group description

Subjects received 2*100 mg and 2*25 mg tablets of JNJ-56136379 once daily during the open-label phase from Day 1 to Week 24.

Reporting group title

Placebo (matching to JNJ-56136379 250 mg) + NA

Reporting group description

Subjects received 2 tablets of matching placebo plus 1 tablet of NA (0.5 mg ETV or 300 mg TDF) once daily from Day 1 to Week 24.

Reporting group title

JNJ-56136379- 250 mg + NA

Reporting group description

Subjects received 2*100 mg and 2*25 mg tablets of JNJ-56136379 plus 1 tablet of NA (0.5 mg ETV or 300 mg TDF) once daily from Day 1 to Week 24.

Subject analysis set title

Placebo + NA (Pooled)

Subject analysis set type

Safety analysis

Subject analysis set description

This analysis set includes subjects who received tablets of matching placebo to JNJ-56136379- 75 mg and JNJ-56136379- 250 mg respectively along with 1 tablet of NA (0.5 mg entecavir [ETV] or 300 mg tenofovir disoproxil fumarate [TDF])

Subject analysis set title

JNJ-56136379 + NA (Pooled)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects in this analysis set included subjects from both JNJ56136379 75mg+ NA and JNJ56136379 250mg+ NA arms respectively

Subject analysis set title

JNJ-56136379 75mg + ETV (Currently not treated)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Currently not treated subjects in this analysis set comprised of all those who were administered JNJ-56136379 75 mg along with the nucleot/side analog- ETV

Subject analysis set title

JNJ-56136379 75mg + TDF (Currently not treated)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Currently not treated subjects in this analysis set comprised of all those who were administered JNJ-56136379 75 mg along with the nucleot/side analog- TDF

Subject analysis set title

JNJ-56136379 75mg + ETV (virologically suppressed)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Virologically- suppressed subjects in this analysis set comprised of all those who were administered JNJ-56136379 75 mg along with the nucleot/side analog- ETV

Subject analysis set title

JNJ-56136379 75mg + TDF (virologically suppressed)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Virologically- suppressed subjects in this analysis set comprised of all those who were administered JNJ-56136379 75 mg along with the nucleot/side analog- TDF

Subject analysis set title

JNJ-56136379 250 mg+ ETV (Currently not treated)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Currently not treated subjects in this analysis set comprised of all those who were administered JNJ-56136379 250 mg along with the nucleot/side analog- ETV

Subject analysis set title

JNJ-56136379 250 mg + TDF (Currently not treated)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Currently not treated subjects in this analysis set comprised of all those who were administered JNJ-56136379 250 mg along with the nucleot/side analog- TDF

Subject analysis set title

JNJ-56136379 250 mg + ETV (virologically suppressed)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Virologically- suppressed subjects in this analysis set comprised of all those who were administered JNJ-56136379 250 mg along with the nucleot/side analog- ETV

Subject analysis set title

JNJ-56136379 250 mg + TDF (virologically suppressed)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Virologically- suppressed subjects in this analysis set comprised of all those who were administered JNJ-56136379 250 mg along with the nucleot/side analog- TDF

Subject analysis set title

Placebo + ETV (virologically suppressed)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subjects in this analysis set received JNJ-56136379 75 mg placebo along with ETV.

Subject analysis set title

Placebo 75 mg + TDF (virologically suppressed)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Virologically suppressed subjects in this analysis set received placebo of JNJ-56136379 75 mg along with TDF

Subject analysis set title

Placebo 250 mg + TDF (virologically suppressed)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Virologically suppressed subjects in this analysis set received placebo of JNJ-56136379 250 mg along with TDF

Subject analysis set title

Placebo + NA (Pooled) [Virologically Suppressed Subjects]

Subject analysis set type

Intention-to-treat

Subject analysis set description

This analysis set includes virologically suppressed subjects who received tablets of matching placebo to JNJ-56136379- 75 mg and JNJ-56136379- 250 mg respectively along with 1 tablet of NA (0.5 mg entecavir [ETV] or 300 mg tenofovir disoproxil fumarate [TDF])

Subject analysis set title

JNJ-56136379 75mg + NA (Virologically Suppressed Subjects)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Virologically- suppressed subjects in this analysis set comprised of all those who were administered JNJ-56136379 75 mg along with the nucleot/side analog

Subject analysis set title

JNJ-56136379 250 mg + NA (Virologically Suppressed Subjects)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Virologically- suppressed subjects in this analysis set comprised of all those who were administered JNJ-56136379 250 mg along with the nucleot/side analog

Subject analysis set title

JNJ-56136379 75 mg + NA (HbeAg Positive)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects in this analysis set comprised of all HbeAg positive subjects who received JNJ-56136379 75 mg+ NA treatment

Subject analysis set title

JNJ-56136379 250 mg + NA (HbeAg positive)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects in this analysis set comprised of HbeAg positive subjects who received JNJ-56136379 250 mg+ NA treatment.

Subject analysis set title

JNJ-56136379 75 mg + NA (HbeAg negative)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects in this analysis set comprised of HbeAg negative subjects who received JNJ-56136379 75 mg + NA treatment.

Subject analysis set title

JNJ-56136379 250 mg + NA (HbeAg negative)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects in this analysis set comprised of HbeAg negative subjects who received JNJ-56136379 250 mg + NA treatment.

Primary: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels at Week 24

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End point title

Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels at Week 24 ^[1] ^[2]

End point description

Change from baseline in HBsAg levels at Week 24 was assessed. Intent-to-Treat Population (ITT) consisted of all subjects who are randomized and received at least one dose of any study agent. If a subject received a study agent other than their randomly assigned study agent, subjects would be shown in the treatment arm as randomized. Here "n" represents number of subjects evaluable for the specified category.

End point type

Primary

End point timeframe

Baseline and Week 24

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: Endpoint was descriptive in nature, no inferential analysis 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: Endpoint was planned to be reported for specified arms only.

End point values	JNJ-56136379- 75 mg (Open label)	JNJ-56136379- 75 mg + NA	JNJ-56136379- 250 mg (Open label)	JNJ-56136379- 250 mg + NA	Placebo + NA (Pooled)
Number of subjects analysed	28	66	32	63	43
Units: log10 IU per milliliter (log10 IU/mL)
arithmetic mean (standard deviation)
HBeAg Positive (n=21,21,8,14,13)	-0.096 ± 0.3567	-0.108 ± 0.2957	-0.203 ± 0.4721	-0.165 ± 0.4491	-0.152 ± 0.2827
HBeAg Negative: (n= 45,38,13,16,28)	0.053 ± 0.2066	0.010 ± 0.0852	0.064 ± 0.0913	0.090 ± 0.1190	0.020 ± 0.0785

No statistical analyses for this end point

Primary: Posterior Probability of JNJ6379+NA over Placebo+NA for HBsAg Change from Baseline (log10) at Week 24 by Hepatitis B e Antigen Status for Currently not Treated Subjects

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End point title

Posterior Probability of JNJ6379+NA over Placebo+NA for HBsAg Change from Baseline (log10) at Week 24 by Hepatitis B e Antigen Status for Currently not Treated Subjects ^[3]

End point description

Posterior Probability of JNJ6379+NA over Placebo+NA for HBsAg change from baseline (log10) at Week 24 by Hepatitis B e antigen status for currently not Treated Subjects was analyzed using Bayesian approach.

End point type

Primary

End point timeframe

Week 24

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: Endpoint was descriptive in nature, no inferential analysis was performed.

End point values	JNJ-56136379 75 mg + NA (HbeAg Positive)	JNJ-56136379 250 mg + NA (HbeAg positive)	JNJ-56136379 75 mg + NA (HbeAg negative)	JNJ-56136379 250 mg + NA (HbeAg negative)
Number of subjects analysed	12	13	21	20
Units: Probability
number (not applicable)	0	4.8	0	0

No statistical analyses for this end point

Primary: Posterior Probability of JNJ6379+NA over Placebo+NA for HBsAg Change from Baseline (log10) at Week 24 by Hepatitis B e Antigen Status for Virologically Suppressed Subjects

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End point title

Posterior Probability of JNJ6379+NA over Placebo+NA for HBsAg Change from Baseline (log10) at Week 24 by Hepatitis B e Antigen Status for Virologically Suppressed Subjects ^[4]

End point description

Posterior probability of JNJ6379+NA over Placebo+NA for HBsAg change from baseline (log10) at Week 24 by Hepatitis B e antigen status for virologically suppressed subjects was analyzed using Bayesian approach.

End point type

Primary

End point timeframe

Week 24

Notes
[4] - 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: Endpoint was descriptive in nature, no inferential analysis was performed.

End point values	JNJ-56136379 75mg + NA (Virologically Suppressed Subjects)	JNJ-56136379 250 mg + NA (Virologically Suppressed Subjects)
Number of subjects analysed	33	30
Units: Probability
number (not applicable)
HbeAg Negative	0	0
HbeAg Positive	0	0

No statistical analyses for this end point

Secondary: Number of Subjects With Treatment- emergent Adverse Events (AEs)

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End point title

Number of Subjects With Treatment- emergent Adverse Events (AEs) ^[5]

End point description

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. The safety population included all subjects who received at least one dose of the study agent; all safety endpoints were analyzed by the treatment arm as treated.

End point type

Secondary

End point timeframe

Up to Week 80

Notes
[5] - 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: Endpoint was planned to be reported for specified arms only.

End point values	JNJ-56136379- 75 mg (Open label)	JNJ-56136379- 75 mg + NA	JNJ-56136379- 250 mg (Open label)	JNJ-56136379- 250 mg + NA	Placebo + NA (Pooled)
Number of subjects analysed	28	66	32	63	43
Units: Subjects	18	55	25	54	34

No statistical analyses for this end point

Secondary: Number of Subjects With Serious Adverse Events (SAEs)

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End point title

Number of Subjects With Serious Adverse Events (SAEs) ^[6]

End point description

A serious adverse event (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. The safety population included all subjects who received at least one dose of the study agent; all safety endpoints were analyzed by the treatment arm as treated.

End point type

Secondary

End point timeframe

Up to Week 80

Notes
[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: Endpoint was planned to be reported for specified arms only.

End point values	JNJ-56136379- 75 mg (Open label)	JNJ-56136379- 75 mg + NA	JNJ-56136379- 250 mg (Open label)	JNJ-56136379- 250 mg + NA	Placebo + NA (Pooled)
Number of subjects analysed	28	66	32	63	43
Units: Subjects	0	3	0	4	1

No statistical analyses for this end point

Secondary: Number of Subjects with Clinically Significant Changes in Vital Signs, Physical Examinations, Electrocardiogram (ECG), and Laboratory Findings

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End point title

Number of Subjects with Clinically Significant Changes in Vital Signs, Physical Examinations, Electrocardiogram (ECG), and Laboratory Findings ^[7]

End point description

Number of subjects with clinically significant changes in vital signs, physical examinations, ECG, and laboratory findings were assessed. The safety population included all subjects who received at least one dose of the study agent; all safety endpoints were analyzed by the treatment arm as treated.

End point type

Secondary

End point timeframe

Up to Week 80

Notes
[7] - 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: Endpoint was planned to be reported for specified arms only.

End point values	JNJ-56136379- 75 mg (Open label)	JNJ-56136379- 75 mg + NA	JNJ-56136379- 250 mg (Open label)	JNJ-56136379- 250 mg + NA	Placebo + NA (Pooled)
Number of subjects analysed	28	66	32	63	43
Units: Subjects	0	0	0	0	0

No statistical analyses for this end point

Secondary: Percentage of Subjects With HBsAg Levels Less Than (<) 1,000 or <100 International Units Per Milliliter (IU/mL) for Currently not Treated Subjects at Week 24

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End point title

Percentage of Subjects With HBsAg Levels Less Than (<) 1,000 or <100 International Units Per Milliliter (IU/mL) for Currently not Treated Subjects at Week 24 ^[8]

End point description

Percentage of subjects with HBsAg levels less than (<) 1,000 or <100 IU/mL for currently not treated subjects at week 24 was assessed. Intent-to-treat (ITT) population: all participants who were randomized and received at least one dose of any study agent. If a participant received a study agent other than their randomly assigned study agent, participants were shown in the treatment arm as randomized.

End point type

Secondary

End point timeframe

Week 24

Notes
[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: Endpoint was planned to be reported for specified arms only.

End point values	JNJ-56136379- 75 mg (Open label)	JNJ-56136379- 75 mg + NA	JNJ-56136379- 250 mg (Open label)	JNJ-56136379- 250 mg + NA	Placebo + NA (Pooled)
Number of subjects analysed	28	33	32	33	22
Units: Percentage of subjects
number (not applicable)
HBsAg<100 IU/mL: HBeAg positive (n=8,12,14,11,8)	0	0	0	0	0
HBsAg<1000 IU/mL: HBeAg positive(n=13,21,16,19,13)	0	0	0	0	0
HBsAg<100 IU/mL: HBeAg negative (n=13,21,16,19,13)	0	0	0	0	0
HBsAg<1000 IU/mL:HBeAg negative (n=13,21,16,19,13)	23.1	4.8	0	10.5	15.4

No statistical analyses for this end point

Secondary: Percentage of Subjects With HBsAg Levels Less Than (<) 1,000 or <100 International Units Per Milliliter (IU/mL) for Virologically Suppressed Subjects at Week 24

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End point title

Percentage of Subjects With HBsAg Levels Less Than (<) 1,000 or <100 International Units Per Milliliter (IU/mL) for Virologically Suppressed Subjects at Week 24

End point description

Percentage of subjects with HBsAg levels less than (<) 1,000 or <100 IU/mL for virologically suppressed subjects at week 24 was assessed. Intent-to-treat (ITT) population: all participants who were randomized and received at least one dose of any study agent. If a participant received a study agent other than their randomly assigned study agent, participants were shown in the treatment arm as randomized.

End point type

Secondary

End point timeframe

Week 24

End point values	Placebo + NA (Pooled) [Virologically Suppressed Subjects]	JNJ-56136379 75mg + NA (Virologically Suppressed Subjects)	JNJ-56136379 250 mg + NA (Virologically Suppressed Subjects)
Number of subjects analysed	21	33	30
Units: Percentage of subjects
number (not applicable)
HBsAg<100 IU/mL: HBeAg positive (n=5,9,10)	0	0	0
HBsAg<1000 IU/mL: HBeAg positive (n=5,9,10)	20	11.1	10
HBsAg<100 IU/mL: HBeAg negative (n=15,24,19)	0	0	0
HBsAg<1000 IU/mL: HBeAg negative (n=15,24,19)	0	29.2	15.8

No statistical analyses for this end point

Secondary: Percentage of Subjects With Greater Than (>) 0.5 log10 IU/mL Reduction in HBsAg From Baseline for Currently-not Treated Subjects at Week 24

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End point title

Percentage of Subjects With Greater Than (>) 0.5 log10 IU/mL Reduction in HBsAg From Baseline for Currently-not Treated Subjects at Week 24 ^[9]

End point description

Percentage of subjects with >0.5 log10 IU/mL reduction in HBsAg from baseline for currently not treated subjects at week 24 was assessed. Intent-to-treat (ITT) population: all participants who were randomized and received at least one dose of any study agent. If a participant received a study agent other than their randomly assigned study agent, participants were shown in the treatment arm as randomized.

End point type

Secondary

End point timeframe

Week 24

Notes
[9] - 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: Endpoint was planned to be reported for specified arms only.

End point values	JNJ-56136379- 75 mg (Open label)	JNJ-56136379- 75 mg + NA	JNJ-56136379- 250 mg (Open label)	JNJ-56136379- 250 mg + NA	Placebo + NA (Pooled)
Number of subjects analysed	8	12	14	11	8
Units: Percentage of subjects
number (not applicable)	12.5	8.3	28.6	36.4	12.5

No statistical analyses for this end point

Secondary: Percentage of Subjects With Greater Than (>) 0.5 log10 IU/mL Reduction in HBsAg From Baseline for Virologically Suppressed Subjects at Week 24

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End point title

Percentage of Subjects With Greater Than (>) 0.5 log10 IU/mL Reduction in HBsAg From Baseline for Virologically Suppressed Subjects at Week 24

End point description

Percentage of subjects with >0.5 log10 IU/mL reduction in HBsAg from baseline for virologically suppressed subjects at week 24 was assessed. Intent-to-treat (ITT) population: all participants who were randomized and received at least one dose of any study agent. If a participant received a study agent other than their randomly assigned study agent, participants were shown in the treatment arm as randomized.

End point type

Secondary

End point timeframe

Week 24

End point values	Placebo + NA (Pooled) [Virologically Suppressed Subjects]	JNJ-56136379 75mg + NA (Virologically Suppressed Subjects)	JNJ-56136379 250 mg + NA (Virologically Suppressed Subjects)
Number of subjects analysed	5	9	10
Units: Percentage of subjects
number (not applicable)	0	0	0

No statistical analyses for this end point

Secondary: Change From Baseline in Hepatitis B Virus (HBV) Deoxyribonucleic acid (DNA) Levels at Week 24 for Currently not Treated HbeAg Positive Subjects

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End point title

Change From Baseline in Hepatitis B Virus (HBV) Deoxyribonucleic acid (DNA) Levels at Week 24 for Currently not Treated HbeAg Positive Subjects ^[10]

End point description

Change from baseline in HBV DNA levels at week 24 for currently not treated HBeAg positive subjects was assessed. Intent-to-treat (ITT) population: all participants who were randomized and received at least one dose of any study agent. If a participant received a study agent other than their randomly assigned study agent, participants were shown in the treatment arm as randomized.

End point type

Secondary

End point timeframe

Baseline and Week 24

Notes
[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: Endpoint was planned to be reported for specified arms only.

End point values	JNJ-56136379- 75 mg (Open label)	JNJ-56136379- 75 mg + NA	JNJ-56136379- 250 mg (Open label)	JNJ-56136379- 250 mg + NA	Placebo + NA (Pooled)
Number of subjects analysed	8	12	14	11	8
Units: log10 IU/mL
arithmetic mean (standard deviation)	-3.284 ± 2.1148	-5.531 ± 0.7915	-5.719 ± 0.8395	-5.883 ± 1.1396	-5.211 ± 1.1986

No statistical analyses for this end point

Secondary: Change From Baseline in Hepatitis B Virus (HBV) Deoxyribonucleic acid (DNA) Levels at Week 24 for Currently not Treated HbeAg Negative Subjects

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End point title

Change From Baseline in Hepatitis B Virus (HBV) Deoxyribonucleic acid (DNA) Levels at Week 24 for Currently not Treated HbeAg Negative Subjects ^[11]

End point description

Change from baseline in HBV DNA levels at week 24 for currently not treated HBeAg negative subjects was assessed. Intent-to-treat (ITT) population: all participants who were randomized and received at least one dose of any study agent. If a participant received a study agent other than their randomly assigned study agent, participants were shown in the treatment arm as randomized.

End point type

Secondary

End point timeframe

Baseline up to Week 24

Notes
[11] - 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: Endpoint was planned to be reported for specified arms only.

End point values	JNJ-56136379- 75 mg (Open label)	JNJ-56136379- 75 mg + NA	JNJ-56136379- 250 mg (Open label)	JNJ-56136379- 250 mg + NA	Placebo + NA (Pooled)
Number of subjects analysed	16	21	18	20	14
Units: log10 IU/mL
arithmetic mean (standard deviation)	-3.469 ± 1.2901	-4.077 ± 0.9435	-3.545 ± 1.1482	-3.690 ± 1.5289	-3.622 ± 1.3003

No statistical analyses for this end point

Secondary: Percentage of Subjects With Undetectable HBV DNA Levels at Week 24 for Currently not Treated Population

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End point title

Percentage of Subjects With Undetectable HBV DNA Levels at Week 24 for Currently not Treated Population ^[12]

End point description

Percentage of subjects with undetectable HBV DNA levels at week 24 for currently not treated population was evaluated. Intent-to-treat (ITT) population: all participants who were randomized and received at least one dose of any study agent. If a participant received a study agent other than their randomly assigned study agent, participants were shown in the treatment arm as randomized. Here "n" represents number of subjects evaluable for the specified category.

End point type

Secondary

End point timeframe

Week 24

Notes
[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: Endpoint was planned to be reported for specified arms only.

End point values	JNJ-56136379- 75 mg (Open label)	JNJ-56136379- 75 mg + NA	JNJ-56136379- 250 mg (Open label)	JNJ-56136379- 250 mg + NA	Placebo + NA (Pooled)
Number of subjects analysed	28	66	32	63	22
Units: Percentage of subjects
number (not applicable)
HBeAg Positive (n= 12,12,14,23,8)	0	0	0	7.7	0
HBeAg Negative (n= 16,21,18,20,14)	12.5	33.3	38.9	35.0	35.7

No statistical analyses for this end point

Secondary: Percentage of Subjects With Undetectable HBV DNA Levels at Week 24 for Virologically Suppressed Population

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End point title

Percentage of Subjects With Undetectable HBV DNA Levels at Week 24 for Virologically Suppressed Population

End point description

Percentage of subjects with undetectable HBV DNA levels at week 24 for virologically suppresed subjects was evaluated. Intent-to-treat (ITT) population: all participants who were randomized and received at least one dose of any study agent. If a participant received a study agent other than their randomly assigned study agent, participants were shown in the treatment arm as randomized. Here "n" represents number of subjects evaluable for the specified category.

End point type

Secondary

End point timeframe

Week 24

End point values	Placebo + NA (Pooled) [Virologically Suppressed Subjects]	JNJ-56136379 75mg + NA (Virologically Suppressed Subjects)	JNJ-56136379 250 mg + NA (Virologically Suppressed Subjects)
Number of subjects analysed	21	33	30
Units: Percentage of subjects
number (not applicable)
HBeAg positive (n= 6,9,10)	50	66.7	90
HBeAg negative (n= 15,24,20)	100	100	90

No statistical analyses for this end point

Secondary: Change From Baseline in Hepatitis B E Antigen (HBeAg) Levels for HBeAg Positive Subjects at Week 24

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End point title

Change From Baseline in Hepatitis B E Antigen (HBeAg) Levels for HBeAg Positive Subjects at Week 24 ^[13]

End point description

Change from baseline in HBeAg levels for HBeAg positive subjects at week 24 was assessed. Intent-to-treat (ITT) population: all participants who were randomized and received at least one dose of any study agent. If a participant received a study agent other than their randomly assigned study agent, participants were shown in the treatment arm as randomized.

End point type

Secondary

End point timeframe

Baseline up to Week 24

Notes
[13] - 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: Endpoint was planned to be reported for specified arms only.

End point values	JNJ-56136379- 75 mg (Open label)	JNJ-56136379- 75 mg + NA	JNJ-56136379- 250 mg (Open label)	JNJ-56136379- 250 mg + NA	Placebo + NA (Pooled)
Number of subjects analysed	8	21	14	21	13
Units: log10 IU/mL
arithmetic mean (standard deviation)	-0.456 ± 0.2908	-0.413 ± 0.3793	-0.974 ± 0.8400	-0.445 ± 0.5618	-0.619 ± 0.7248

No statistical analyses for this end point

Secondary: Percentage of Subjects by HBeAg Levels Reduced from Baseline >0.5 log10 IU/mL and >1 log10 IU/mL for Currently not Treated Subjects at Week 24

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End point title

Percentage of Subjects by HBeAg Levels Reduced from Baseline >0.5 log10 IU/mL and >1 log10 IU/mL for Currently not Treated Subjects at Week 24 ^[14]

End point description

Percentage of subjects by HBeAg levels reduced from baseline >0.5 log10 IU/mL and >1 log10 IU/mL for currently not treated subjects at week 24 was evaluated. Intent-to-treat (ITT) population: all participants who were randomized and received at least one dose of any study agent. If a participant received a study agent other than their randomly assigned study agent, participants were shown in the treatment arm as randomized.

End point type

Secondary

End point timeframe

Week 24

Notes
[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: Endpoint was planned to be reported for specified arms only.

End point values	JNJ-56136379- 75 mg (Open label)	JNJ-56136379- 75 mg + NA	JNJ-56136379- 250 mg (Open label)	JNJ-56136379- 250 mg + NA	Placebo + NA (Pooled)
Number of subjects analysed	8	12	14	11	8
Units: Percentage of subjects
number (not applicable)
Reduction from Baseline at Wk 24: >0.5 log10 IU/mL	50	41.7	78.6	63.6	62.5
Reduction from Baseline at Wk 24: >1 log10 IU/mL	0	8.3	42.9	36.4	37.5

No statistical analyses for this end point

Secondary: Percentage of Subjects by HBeAg Levels Reduced from Baseline >0.5 log10 IU/mL and >1 log10 IU/mL for Virologically Suppressed Subjects at Week 24

Top of page

End point title

Percentage of Subjects by HBeAg Levels Reduced from Baseline >0.5 log10 IU/mL and >1 log10 IU/mL for Virologically Suppressed Subjects at Week 24

End point description

Percentage of subjects by HBeAg levels reduced from baseline >0.5 log10 IU/mL and >1 log10 IU/mL for virologically suppressed subjects at week 24 was evaluated. Intent-to-treat (ITT) population: all participants who were randomized and received at least one dose of any study agent. If a participant received a study agent other than their randomly assigned study agent, participants were shown in the treatment arm as randomized.

End point type

Secondary

End point timeframe

Week 24

End point values	Placebo + NA (Pooled) [Virologically Suppressed Subjects]	JNJ-56136379 75mg + NA (Virologically Suppressed Subjects)	JNJ-56136379 250 mg + NA (Virologically Suppressed Subjects)
Number of subjects analysed	5	9	10
Units: Percentage of subjects
number (not applicable)
Reduction from Baseline at Wk 24: >0.5 log10 IU/mL	20	33.3	10
Reduction from Baseline at Wk 24: >1 log10 IU/mL	20	11.1	0

No statistical analyses for this end point

Secondary: Number of Subjects With HBsAg Seroclearance

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End point title

Number of Subjects With HBsAg Seroclearance ^[15]

End point description

Number of subjects with HBsAg seroclearance was assessed. Intent-to-treat (ITT) population: all participants who were randomized and received at least one dose of any study agent. If a participant received a study agent other than their randomly assigned study agent, participants were shown in the treatment arm as randomized.

End point type

Secondary

End point timeframe

Week 24

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: Endpoint was planned to be reported for specified arms only.

End point values	JNJ-56136379- 75 mg (Open label)	JNJ-56136379- 75 mg + NA	JNJ-56136379- 250 mg (Open label)	JNJ-56136379- 250 mg + NA	Placebo + NA (Pooled)	Placebo + NA (Pooled) [Virologically Suppressed Subjects]	JNJ-56136379 75mg + NA (Virologically Suppressed Subjects)	JNJ-56136379 250 mg + NA (Virologically Suppressed Subjects)
Number of subjects analysed	28	66	32	63	43	21	33	30
Units: Subjects
Week 24	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Number of Subjects With HBsAg Seroconversion

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End point title

Number of Subjects With HBsAg Seroconversion ^[16]

End point description

Number of subjects with HBsAg seroconversion was assessed. Intent-to-treat (ITT) population: all participants who were randomized and received at least one dose of any study agent. If a participant received a study agent other than their randomly assigned study agent, participants were shown in the treatment arm as randomized.

End point type

Secondary

End point timeframe

Week 24

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: Endpoint was planned to be reported for specified arms only.

End point values	JNJ-56136379- 75 mg (Open label)	JNJ-56136379- 75 mg + NA	JNJ-56136379- 250 mg (Open label)	JNJ-56136379- 250 mg + NA	Placebo + NA (Pooled)	Placebo + NA (Pooled) [Virologically Suppressed Subjects]
Number of subjects analysed	28	66	32	63	43	21
Units: Subjects
Week 24	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Percentage of Subjects With Normalized Alanine Aminotransferase (ALT) Levels for Currently not Treated Population at Week 24

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End point title

Percentage of Subjects With Normalized Alanine Aminotransferase (ALT) Levels for Currently not Treated Population at Week 24 ^[17]

End point description

Percentage of subjects with normalized alanine aminotransferase (ALT) levels for currently not treated population at week 24 was assessed ,whose ALT levels were above upper limit of normal at baseline. Safety population: all participants who received at least one dose of the study agent; all safety endpoints were analyzed by the treatment arm as treated. Here "n" represents number of subjects evaluable for the specified category.

End point type

Secondary

End point timeframe

Week 24

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: Endpoint was planned to be reported for specified arms only.

End point values	JNJ-56136379- 75 mg (Open label)	JNJ-56136379- 75 mg + NA	JNJ-56136379- 250 mg (Open label)	JNJ-56136379- 250 mg + NA	Placebo + NA (Pooled)
Number of subjects analysed	23	27	26	27	18
Units: Percentage of subjects
number (not applicable)
HBeAg positive (n=8,11,14,11,8)	60	54.5	64.3	44.4	62.5
HBeAg negative (n=15,16,12,16,10)	91.7	68.8	72.7	80	55.6

No statistical analyses for this end point

Secondary: Percentage of Subjects With Normalized Alanine Aminotransferase (ALT) Levels for Virologically Suppressed Population at Week 24

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End point title

Percentage of Subjects With Normalized Alanine Aminotransferase (ALT) Levels for Virologically Suppressed Population at Week 24

End point description

Percentage of subjects with normalized alanine aminotransferase (ALT) levels for virologically suppressed population at week 24 was assessed ,whose ALT levels were above upper limit of normal at baseline. Safety population: all participants who received at least one dose of the study agent; all safety endpoints were analyzed by the treatment arm as treated. Here "n" represents number of subjects evaluable for the specified category.

End point type

Secondary

End point timeframe

Week 24

End point values	Placebo + NA (Pooled) [Virologically Suppressed Subjects]	JNJ-56136379 75mg + NA (Virologically Suppressed Subjects)	JNJ-56136379 250 mg + NA (Virologically Suppressed Subjects)
Number of subjects analysed	3	4	5
Units: Percentage of subjects
number (not applicable)
HBeAg Positive (n= 1,1,3)	0	100	33.3
HBeAg Negative (n= 2,3,2)	50	100	0

No statistical analyses for this end point

Secondary: Number of Subjects With Virological Breakthrough

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End point title

Number of Subjects With Virological Breakthrough ^[18]

End point description

Number of subjects with viral breakthrough defined as confirmed on treatment HBV DNA increase by greater than (>) 1 log10 from nadir level or confirmed on treatment level >200 International Units Per Milliliter (IU/mL) in participants who had HBV DNA level below the lower limit of quantification (LLOQ) of the HBV DNA assay. Intent-to-Treat Population (ITT) consisted of all subjects who are randomized and received at least one dose of any study agent. If a subject receives a study agent other than their randomly assigned study agent, subjects will be shown in the treatment arm as randomized.

End point type

Secondary

End point timeframe

Up to Week 80

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: Endpoint was planned to be reported for specified arms only.

End point values	JNJ-56136379- 75 mg (Open label)	JNJ-56136379- 75 mg + NA	JNJ-56136379- 250 mg (Open label)	JNJ-56136379- 250 mg + NA	Placebo + NA (Pooled)
Number of subjects analysed	28	66	32	63	43
Units: Subjects
Viral breakthrough during 24 weeks	5	0	1	0	0
Breakthrough b/w 25 & 48 weeks(n=3,43,20,48,33)	1	1	0	0	0
Breakthrough for NA treatment (n= 24,64,29,60,40)	0	2	2	2	1

No statistical analyses for this end point

Secondary: Plasma Concentrations of Entecavir [ETV]

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End point title

Plasma Concentrations of Entecavir [ETV]

End point description

Plasma concentrations of ETV administered as monotherapy or co-administered with JNJ-56136379 was determined. The pharmacokinetic (PK) analysis set included data for all subjects with available plasma concentrations. "99999" denotes timepoints in particular arms which do not have any value.

End point type

Secondary

End point timeframe

Day1: 0 hours (h), Day 1: 2h, Week (W)1: 0h, W2:0h, W4: 0h, W8: 0h, W12: 0h, W20: 0h, W24: 0h, W28: 0h, W32: 0h, W36: 0h, W44: 0h, W48: 0h, Follow-up (FU): W2, FU: W4

End point values	JNJ-56136379 75mg + ETV (Currently not treated)	JNJ-56136379 75mg + ETV (virologically suppressed)	JNJ-56136379 250 mg+ ETV (Currently not treated)	JNJ-56136379 250 mg + ETV (virologically suppressed)	Placebo + ETV (virologically suppressed)
Number of subjects analysed	9	15	7	9	6
Units: nanograms per milliliter (ng/ml)
arithmetic mean (standard deviation)
D1: 0h	99999 ± 99999	0.683 ± 0.414	99999 ± 99999	99999 ± 99999	99999 ± 99999
D1: 2h	1.39 ± 0.709	1.86 ± 0.639	1.18 ± 0.197	1.89 ± 0.429	99999 ± 99999
W1: 0h	0.321 ± 0.0961	0.464 ± 0.143	0.289 ± 0.0351	0.472 ± 0.120	1.94 ± 2.43
W2: 0h	0.285 ± 0.166	0.469 ± 0.153	0.377 ± 0.0531	0.469 ± 0.0835	0.871 ± 0.909
W4: 0h	0.417 ± 0.143	0.529 ± 0.198	0.414 ± 0.0742	0.539 ± 0.108	0.647 ± 0.628
W8: 0h	0.353 ± 0.226	0.496 ± 0.179	0.466 ± 0.0913	0.493 ± 0.0816	99999 ± 99999
W12: 0h	0.467 ± 0.188	0.454 ± 0.135	0.479 ± 0.0650	0.548 ± 0.0535	0.277 ± 0.0733
W20: 0h	0.441 ± 0.147	0.617 ± 0.408	0.481 ± 0.0625	0.537 ± 0.109	99999 ± 99999
W24: 0h	0.395 ± 0.309	0.491 ± 0.144	0.385 ± 0.0415	0.576 ± 0.121	99999 ± 99999
W28: 0h	99999 ± 99999	0.446 ± 0.148	0.527 ± 0.0302	0.519 ± 0.153	99999 ± 99999
W32: 0h	99999 ± 99999	0.467 ± 0.201	0.462 ± 0.0410	0.489 ± 0.114	99999 ± 99999
W36: 0h	99999 ± 99999	0.487 ± 0.185	0.442 ± 0.0517	0.526 ± 0.109	0.962 ± 1.07
W44: 0h	99999 ± 99999	0.525 ± 0.177	0.438 ± 0.0352	0.517 ± 0.121	99999 ± 99999
W48: 0h	0.434 ± 0.0968	0.554 ± 0.287	0.539 ± 0.0414	0.537 ± 0.105	0.766 ± 0.594
FU: W2	0.542 ± 0.311	0.635 ± 0.449	0.307 ± 0.176	0.433 ± 0.117	99999 ± 99999
FU: W4	0.354 ± 0.260	0.445 ± 0.164	0.309 ± 0.161	0.725 ± 0.598	1.00 ± 1.13

No statistical analyses for this end point

Secondary: Plasma Concentrations of Tenofovir (TFV) for Currently not Treated and Virologically Suppressed Population

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End point title

Plasma Concentrations of Tenofovir (TFV) for Currently not Treated and Virologically Suppressed Population ^[19]

End point description

Plasma concentrations of TFV for currently not treated and virologically suppressed population administered as monotherapy or co-administered with JNJ-56136379 was determined. The PK analysis set included data for all subjects with available plasma concentrations. "99999" denotes timepoints in particular arms which do not have any value.

End point type

Secondary

End point timeframe

Day1: 0 hours (h), Day 1: 2h, Week (W)1: 0h, W2:0h, W4: 0h, W8: 0h, W12: 0h, W16: 0h, W20: 0h, W24: 0h, W28: 0h, W32: 0h, W36: 0h, W40: 0h, W44: 0h, W48: 0h, Follow-up (FU): W2, FU: W4

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: Endpoint was planned to be reported for specified arms only.

End point values	Placebo (matching JNJ-6379 75mg) + Nucleos(t)ide analog (NA)	Placebo (matching to JNJ-56136379 250 mg) + NA	JNJ-56136379 75mg + TDF (Currently not treated)	JNJ-56136379 75mg + TDF (virologically suppressed)	JNJ-56136379 250 mg + TDF (Currently not treated)	JNJ-56136379 250 mg + TDF (virologically suppressed)	Placebo 75 mg + TDF (virologically suppressed)	Placebo 250 mg + TDF (virologically suppressed)
Number of subjects analysed	9	8	24	18	26	21	5	8
Units: nanograms per milliliter (ng/ml)
arithmetic mean (standard deviation)
D1: 0h	99999 ± 99999	99999 ± 99999	99999 ± 99999	68.9 ± 10.1	99999 ± 99999	63.3 ± 27.4	99999 ± 99999	99999 ± 99999
D1: 2h	277 ± 116	170 ± 114	372 ± 478	306 ± 145	249 ± 96.9	364 ± 260	274 ± 153	311 ± 92.5
W1: 0h	79.6 ± 38.1	92.7 ± 134	92.6 ± 37.4	97.9 ± 38.0	97.8 ± 27.7	97.1 ± 36.8	76.8 ± 40.8	59.2 ± 15.7
W2: 0h	64.2 ± 34.5	50.1 ± 14.1	81.5 ± 22.6	97.5 ± 34.0	97.6 ± 23.7	114 ± 51.0	82.0 ± 53.0	65.9 ± 18.9
W4: 0h	62.9 ± 17.7	46.5 ± 10.5	90.2 ± 25.8	96.9 ± 25.0	99.6 ± 26.4	110 ± 41.4	83.1 ± 54.8	66.9 ± 20.3
W8: 0h	66.3 ± 23.7	54.2 ± 18.3	92.6 ± 25.7	118 ± 48.0	108 ± 36.0	109 ± 32.2	84.0 ± 54.1	65.5 ± 28.9
W12: 0h	67.5 ± 31.2	51.3 ± 15.9	93.5 ± 29.1	99.4 ± 33.8	102 ± 35.3	130 ± 87.8	98.8 ± 73.6	63.5 ± 21.6
W16: 0h	99999 ± 99999	47.5 ± 25.4	99999 ± 99999	99999 ± 99999	77.8 ± 15.0	99999 ± 99999	99999 ± 99999	99999 ± 99999
W20: 0h	72.6 ± 34.2	51.2 ± 13.8	85.8 ± 30.6	120 ± 30.1	115 ± 41.7	127 ± 64.9	99.6 ± 85.0	64.8 ± 23.3
W24: 0h	75.9 ± 51.0	50.5 ± 20.1	89.1 ± 30.1	104 ± 29.9	99.3 ± 37.8	113 ± 47.6	78.3 ± 33.4	73.8 ± 33.0
W28: 0h	74.4 ± 38.1	51.2 ± 19.9	99.0 ± 32.6	110 ± 43.2	108 ± 39.0	155 ± 107	81.7 ± 37.7	70.6 ± 28.1
W32: 0h	78.8 ± 59.6	52.7 ± 26.1	89.6 ± 37.1	106 ± 36.4	88.5 ± 25.6	139 ± 93.3	75.5 ± 54.8	61.2 ± 21.2
W36: 0h	78.9 ± 55.8	42.5 ± 19.3	96.0 ± 38.3	101 ± 33.1	101 ± 34.2	132 ± 90.2	80.2 ± 50.3	80.2 ± 31.2
W40: 0h	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
W44: 0h	86.3 ± 30.8	46.3 ± 26.0	81.8 ± 38.9	109 ± 53.4	105 ± 33.5	129 ± 73.6	72.7 ± 54.9	93.0 ± 64.2
W48: 0h	76.4 ± 40	47.8 ± 18.6	89.5 ± 49.8	114 ± 31.7	100 ± 29.9	133 ± 117	87.6 ± 58.5	66.2 ± 22.1
FU: W2	73.8 ± 37.1	52.1 ± 17.3	65.7 ± 29.5	73.2 ± 18.5	73.5 ± 23.2	136 ± 95.5	86.5 ± 73.8	51.9 ± 23.4
FU: W4	72.4 ± 32.1	57.1 ± 13.6	68.7 ± 54.3	71.2 ± 33.0	68.4 ± 43.6	95.8 ± 83.6	74.7 ± 47.6	59.7 ± 23.4

No statistical analyses for this end point

Secondary: Plasma Concentrations of JNJ-56136379 for Currently not Treated and Virologically Suppressed Population

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End point title

Plasma Concentrations of JNJ-56136379 for Currently not Treated and Virologically Suppressed Population ^[20]

End point description

Plasma concentrations of JNJ-56136379 for currently not treated and virologically suppressed population administered as monotherapy or when co-administered with NA (ETV or TDF) was determined. The PK analysis set included data for all subjects with available plasma concentrations. "99999" denotes timepoints in particular arms which do not have any value.

End point type

Secondary

End point timeframe

Day1: 0 hours (h), Day 1: 2h, Week (W)1: 0h, W2:0h, W4: 0h, W8: 0h, W12: 0h, W16: 0h, W20: 0h, W24: 0h, W28: 0h, W32: 0h, W36: 0h, W40: 0h, W44: 0h, W48: 0h, Follow-up (FU): W2, FU: W4

Notes
[20] - 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: Endpoint was planned to be reported for specified arms only.

End point values	JNJ-56136379- 75 mg (Open label)	JNJ-56136379- 250 mg (Open label)	JNJ-56136379 75mg + ETV (Currently not treated)	JNJ-56136379 75mg + TDF (Currently not treated)	JNJ-56136379 75mg + ETV (virologically suppressed)	JNJ-56136379 75mg + TDF (virologically suppressed)	JNJ-56136379 250 mg+ ETV (Currently not treated)	JNJ-56136379 250 mg + TDF (Currently not treated)	JNJ-56136379 250 mg + ETV (virologically suppressed)	JNJ-56136379 250 mg + TDF (virologically suppressed)
Number of subjects analysed	28	32	9	24	15	18	7	26	9	21
Units: nanograms per milliliter (ng/ml)
arithmetic mean (standard deviation)
D1: 0h	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
D1:2h	709 ± 307	2143 ± 1300	520 ± 279	820 ± 306	857 ± 238	616 ± 385	2287 ± 946	2021 ± 893	2103 ± 1400	2083 ± 1022
W1: 0h	2269 ± 597	7339 ± 2040	2264 ± 455	2368 ± 695	2144 ± 553	2301 ± 639	6461 ± 2014	7138 ± 2280	5758 ± 1081	7280 ± 2098
W2: 0h	3424 ± 845	10894 ± 2631	3094 ± 892	3702 ± 1028	3193 ± 1017	3206 ± 710	9381 ± 2168	10588 ± 3568	8485 ± 2269	10077 ± 2886
W4: 0h	4116 ± 941	12827 ± 3104	4368 ± 1216	4697 ± 1474	3689 ± 1178	3694 ± 815	10760 ± 2162	12513 ± 4229	10106 ± 2838	12167 ± 4271
W08: 0h	4617 ± 1195	13697 ± 3702	5006 ± 1258	4719 ± 1465	3917 ± 1131	3998 ± 1376	11027 ± 2009	13037 ± 4394	11295 ± 3829	13352 ± 6072
W12: 0h	4130 ± 1145	12676 ± 3431	4976 ± 1302	4582 ± 1324	4194 ± 1279	3813 ± 945	11347 ± 1754	12524 ± 4756	10404 ± 4246	12776 ± 5191
W16: 0h	99999 ± 99999	11333 ± 2639	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	12316 ± 1947	99999 ± 99999	99999 ± 99999
W20: 0h	3754 ± 1132	12757 ± 4298	4648 ± 1508	4698 ± 1661	3948 ± 1151	4134 ± 1375	10517 ± 2031	11425 ± 3719	10761 ± 3980	12432 ± 4249
W24: 0h	3613 ± 813	12626 ± 3396	4650 ± 1461	4767 ± 1601	3989 ± 957	3836 ± 1160	10888 ± 1576	11625 ± 5087	10219 ± 3370	11542 ± 4612
W28:0h	4733 ± 350	12025 ± 3229	4300 ± 1355	4439 ± 1446	4259 ± 1083	3506 ± 1032	11753 ± 2719	11746 ± 4752	9959 ± 2929	11344 ± 4482
W32: 0h	99999 ± 99999	12162 ± 2780	4677 ± 646	4825 ± 2429	3788 ± 841	3721 ± 1088	9840 ± 3770	12119 ± 4062	10189 ± 3160	12099 ± 6301
W36: 0h	99999 ± 99999	11289 ± 2973	4463 ± 1444	4144 ± 1599	3801 ± 1170	3535 ± 964	11350 ± 3439	11192 ± 5191	10036 ± 2786	12227 ± 5396
W40: 0h	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
W44: 0h	99999 ± 99999	11198 ± 2749	4507 ± 1121	3430 ± 1346	3998 ± 1139	3784 ± 1056	11570 ± 2674	11016 ± 4277	9634 ± 3707	14853 ± 7977
W48: 0h	99999 ± 99999	11797 ± 2482	99999 ± 99999	99999 ± 99999	3918 ± 1259	99999 ± 99999	11220 ± 2464	10740 ± 2400	99999 ± 99999	15080 ± 8060
FU: W2	916 ± 930	2459 ± 1529	1330 ± 887	909 ± 740	621 ± 607	912 ± 585	1922 ± 1628	2192 ± 1535	1919 ± 1359	3190 ± 4462
FU: W4	242 ± 359	494 ± 427	320 ± 276	226 ± 236	89.8 ± 102	204 ± 209	572 ± 624	1025 ± 1523	389 ± 384	1066 ± 2319

No statistical analyses for this end point

Secondary: Number of Subjects With Treatment-Associated Mutations

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End point title

Number of Subjects With Treatment-Associated Mutations ^[21]

End point description

Viral genome sequence analysis was performed to evaluate emergence of mutations associated with JNJ-56136379 considering 15 HBV core protein positions of interest. Intent-to-treat (ITT) population: all participants who were randomized and received at least one dose of any study agent. If a participant received a study agent other than their randomly assigned study agent, participants were shown in the treatment arm as randomized. Here number of subjects analyzed corresponds to the number of subjects with paired baseline and post-baseline sequence info available.

End point type

Secondary

End point timeframe

Up to Week 80

Notes
[21] - 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: Endpoint was planned to be reported for specified arms only.

End point values	JNJ-56136379- 75 mg (Open label)	JNJ-56136379- 75 mg + NA	JNJ-56136379- 250 mg (Open label)	JNJ-56136379- 250 mg + NA	Placebo + NA (Pooled)
Number of subjects analysed	23	22	17	14	11
Units: Subjects
Emergence of mutations during 24 weeks	8	0	4	0	0
Emergence of mutations between 25 and 48 weeks	2	0	0	0	0
Emergence of mutations on NA treatment	0	0	0	0	0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Up to 104 weeks

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

23.0

Reporting group title

JNJ-56136379-75 mg (Open label)

Reporting group description

Subjects currently not treated received 3*25 milligrams (mg) tablets of JNJ-56136379 once daily during the open label phase from Day 1 to Week 24.

Reporting group title

Placebo (matching JNJ-6379 75 mg) + Nucleos(t)ide analog (NA)

Reporting group description

Subjects received 3 tablets of matching placebo plus 1 tablet of NA (0.5 mg entecavir [ETV] or 300 mg tenofovir disoproxil fumarate [TDF]) once daily from Day 1 to Week 24.

Reporting group title

JNJ-56136379- 75 mg + NA

Reporting group description

Subjects received 3*25 mg tablets of JNJ-56136379 plus 1 tablet of NA (0.5 mg ETV or 300 mg TDF) once daily from Day 1 to Week 24.

Reporting group title

JNJ-56136379- 250 mg (Open label)

Reporting group description

Subjects received 2*100 mg and 2*25 mg tablets of JNJ-56136379 once daily during the open-label phase from Day 1 to Week 24.

Reporting group title

Placebo (matching to JNJ-56136379 250 mg) + NA

Reporting group description

Subjects received 2 tablets of matching placebo plus 1 tablet of NA (0.5 mg ETV or 300 mg TDF) once daily from Day 1 to Week 24.

Reporting group title

JNJ-56136379- 250 mg + NA

Reporting group description

Subjects received 2*100 mg and 2*25 mg tablets of JNJ-56136379 plus 1 tablet of NA (0.5 mg ETV or 300 mg TDF) once daily from Day 1 to Week 24.

Serious adverse events	JNJ-56136379-75 mg (Open label)	Placebo (matching JNJ-6379 75 mg) + Nucleos(t)ide analog (NA)	JNJ-56136379- 75 mg + NA	JNJ-56136379- 250 mg (Open label)	Placebo (matching to JNJ-56136379 250 mg) + NA	JNJ-56136379- 250 mg + NA
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 28 (3.57%)	0 / 21 (0.00%)	4 / 66 (6.06%)	0 / 32 (0.00%)	1 / 22 (4.55%)	4 / 63 (6.35%)
number of deaths (all causes)	0	0	0	0	0	0
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung Adenocarcinoma
subjects affected / exposed	0 / 28 (0.00%)	0 / 21 (0.00%)	1 / 66 (1.52%)	0 / 32 (0.00%)	0 / 22 (0.00%)	0 / 63 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Ligament Rupture
subjects affected / exposed	0 / 28 (0.00%)	0 / 21 (0.00%)	0 / 66 (0.00%)	0 / 32 (0.00%)	0 / 22 (0.00%)	1 / 63 (1.59%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Post-Traumatic Neck Syndrome
subjects affected / exposed	0 / 28 (0.00%)	0 / 21 (0.00%)	1 / 66 (1.52%)	0 / 32 (0.00%)	0 / 22 (0.00%)	0 / 63 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Cardiac Failure Acute
subjects affected / exposed	0 / 28 (0.00%)	0 / 21 (0.00%)	1 / 66 (1.52%)	0 / 32 (0.00%)	0 / 22 (0.00%)	0 / 63 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myocarditis
subjects affected / exposed	0 / 28 (0.00%)	0 / 21 (0.00%)	1 / 66 (1.52%)	0 / 32 (0.00%)	0 / 22 (0.00%)	0 / 63 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Lymphadenitis
subjects affected / exposed	0 / 28 (0.00%)	0 / 21 (0.00%)	1 / 66 (1.52%)	0 / 32 (0.00%)	0 / 22 (0.00%)	0 / 63 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Colitis
subjects affected / exposed	0 / 28 (0.00%)	0 / 21 (0.00%)	0 / 66 (0.00%)	0 / 32 (0.00%)	1 / 22 (4.55%)	0 / 63 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Ovarian Haemorrhage
subjects affected / exposed	0 / 28 (0.00%)	0 / 21 (0.00%)	0 / 66 (0.00%)	0 / 32 (0.00%)	0 / 22 (0.00%)	1 / 63 (1.59%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	1 / 28 (3.57%)	0 / 21 (0.00%)	0 / 66 (0.00%)	0 / 32 (0.00%)	0 / 22 (0.00%)	0 / 63 (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
Musculoskeletal and connective tissue disorders
Intervertebral Disc Protrusion
subjects affected / exposed	0 / 28 (0.00%)	0 / 21 (0.00%)	0 / 66 (0.00%)	0 / 32 (0.00%)	0 / 22 (0.00%)	1 / 63 (1.59%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Muscle Necrosis
subjects affected / exposed	0 / 28 (0.00%)	0 / 21 (0.00%)	1 / 66 (1.52%)	0 / 32 (0.00%)	0 / 22 (0.00%)	0 / 63 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Appendicitis
subjects affected / exposed	0 / 28 (0.00%)	0 / 21 (0.00%)	0 / 66 (0.00%)	0 / 32 (0.00%)	0 / 22 (0.00%)	1 / 63 (1.59%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Toxic Shock Syndrome Streptococcal
subjects affected / exposed	0 / 28 (0.00%)	0 / 21 (0.00%)	1 / 66 (1.52%)	0 / 32 (0.00%)	0 / 22 (0.00%)	0 / 63 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	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	JNJ-56136379-75 mg (Open label)	Placebo (matching JNJ-6379 75 mg) + Nucleos(t)ide analog (NA)	JNJ-56136379- 75 mg + NA	JNJ-56136379- 250 mg (Open label)	Placebo (matching to JNJ-56136379 250 mg) + NA	JNJ-56136379- 250 mg + NA
Total subjects affected by non serious adverse events
subjects affected / exposed	18 / 28 (64.29%)	13 / 21 (61.90%)	46 / 66 (69.70%)	23 / 32 (71.88%)	14 / 22 (63.64%)	45 / 63 (71.43%)
Investigations
Alanine Aminotransferase Increased
subjects affected / exposed	1 / 28 (3.57%)	1 / 21 (4.76%)	2 / 66 (3.03%)	3 / 32 (9.38%)	1 / 22 (4.55%)	6 / 63 (9.52%)
occurrences all number	1	1	11	3	1	11
Amylase Increased
subjects affected / exposed	3 / 28 (10.71%)	1 / 21 (4.76%)	1 / 66 (1.52%)	1 / 32 (3.13%)	0 / 22 (0.00%)	3 / 63 (4.76%)
occurrences all number	6	3	1	4	0	7
Aspartate Aminotransferase Increased
subjects affected / exposed	1 / 28 (3.57%)	0 / 21 (0.00%)	2 / 66 (3.03%)	1 / 32 (3.13%)	1 / 22 (4.55%)	4 / 63 (6.35%)
occurrences all number	1	0	7	1	1	7
Blood Creatine Phosphokinase Increased
subjects affected / exposed	1 / 28 (3.57%)	2 / 21 (9.52%)	4 / 66 (6.06%)	1 / 32 (3.13%)	1 / 22 (4.55%)	1 / 63 (1.59%)
occurrences all number	1	3	5	1	1	1
Glomerular Filtration Rate Decreased
subjects affected / exposed	0 / 28 (0.00%)	0 / 21 (0.00%)	3 / 66 (4.55%)	3 / 32 (9.38%)	0 / 22 (0.00%)	1 / 63 (1.59%)
occurrences all number	0	0	3	3	0	1
Injury, poisoning and procedural complications
Overdose
subjects affected / exposed	0 / 28 (0.00%)	0 / 21 (0.00%)	4 / 66 (6.06%)	0 / 32 (0.00%)	0 / 22 (0.00%)	1 / 63 (1.59%)
occurrences all number	0	0	5	0	0	1
Nervous system disorders
Dizziness
subjects affected / exposed	1 / 28 (3.57%)	0 / 21 (0.00%)	3 / 66 (4.55%)	4 / 32 (12.50%)	0 / 22 (0.00%)	2 / 63 (3.17%)
occurrences all number	1	0	3	6	0	2
Headache
subjects affected / exposed	3 / 28 (10.71%)	3 / 21 (14.29%)	11 / 66 (16.67%)	7 / 32 (21.88%)	1 / 22 (4.55%)	14 / 63 (22.22%)
occurrences all number	4	3	23	8	1	22
General disorders and administration site conditions
Chest Discomfort
subjects affected / exposed	0 / 28 (0.00%)	0 / 21 (0.00%)	1 / 66 (1.52%)	2 / 32 (6.25%)	0 / 22 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	1	2	0	0
Fatigue
subjects affected / exposed	2 / 28 (7.14%)	4 / 21 (19.05%)	8 / 66 (12.12%)	2 / 32 (6.25%)	0 / 22 (0.00%)	5 / 63 (7.94%)
occurrences all number	4	4	8	2	0	7
Influenza Like Illness
subjects affected / exposed	2 / 28 (7.14%)	1 / 21 (4.76%)	2 / 66 (3.03%)	0 / 32 (0.00%)	0 / 22 (0.00%)	0 / 63 (0.00%)
occurrences all number	2	1	2	0	0	0
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	1 / 28 (3.57%)	2 / 21 (9.52%)	0 / 66 (0.00%)	0 / 32 (0.00%)	1 / 22 (4.55%)	0 / 63 (0.00%)
occurrences all number	1	2	0	0	1	0
Gastrointestinal disorders
Abdominal Pain
subjects affected / exposed	0 / 28 (0.00%)	1 / 21 (4.76%)	1 / 66 (1.52%)	1 / 32 (3.13%)	0 / 22 (0.00%)	5 / 63 (7.94%)
occurrences all number	0	2	1	1	0	5
Abdominal Pain Upper
subjects affected / exposed	1 / 28 (3.57%)	1 / 21 (4.76%)	3 / 66 (4.55%)	2 / 32 (6.25%)	0 / 22 (0.00%)	5 / 63 (7.94%)
occurrences all number	1	1	3	2	0	7
Constipation
subjects affected / exposed	2 / 28 (7.14%)	0 / 21 (0.00%)	1 / 66 (1.52%)	3 / 32 (9.38%)	0 / 22 (0.00%)	1 / 63 (1.59%)
occurrences all number	2	0	1	3	0	2
Diarrhoea
subjects affected / exposed	2 / 28 (7.14%)	1 / 21 (4.76%)	4 / 66 (6.06%)	1 / 32 (3.13%)	0 / 22 (0.00%)	5 / 63 (7.94%)
occurrences all number	2	1	4	1	0	6
Nausea
subjects affected / exposed	2 / 28 (7.14%)	2 / 21 (9.52%)	2 / 66 (3.03%)	2 / 32 (6.25%)	1 / 22 (4.55%)	5 / 63 (7.94%)
occurrences all number	3	3	2	2	1	6
Toothache
subjects affected / exposed	0 / 28 (0.00%)	0 / 21 (0.00%)	5 / 66 (7.58%)	1 / 32 (3.13%)	0 / 22 (0.00%)	2 / 63 (3.17%)
occurrences all number	0	0	5	2	0	2
Hepatobiliary disorders
Hepatic Pain
subjects affected / exposed	2 / 28 (7.14%)	0 / 21 (0.00%)	1 / 66 (1.52%)	0 / 32 (0.00%)	0 / 22 (0.00%)	0 / 63 (0.00%)
occurrences all number	2	0	1	0	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	0 / 28 (0.00%)	0 / 21 (0.00%)	2 / 66 (3.03%)	3 / 32 (9.38%)	1 / 22 (4.55%)	2 / 63 (3.17%)
occurrences all number	0	0	2	3	1	2
Oropharyngeal Pain
subjects affected / exposed	2 / 28 (7.14%)	1 / 21 (4.76%)	2 / 66 (3.03%)	0 / 32 (0.00%)	0 / 22 (0.00%)	4 / 63 (6.35%)
occurrences all number	2	1	2	0	0	6
Skin and subcutaneous tissue disorders
Pruritus
subjects affected / exposed	2 / 28 (7.14%)	1 / 21 (4.76%)	1 / 66 (1.52%)	0 / 32 (0.00%)	0 / 22 (0.00%)	5 / 63 (7.94%)
occurrences all number	2	2	1	0	0	9
Rash
subjects affected / exposed	0 / 28 (0.00%)	1 / 21 (4.76%)	4 / 66 (6.06%)	4 / 32 (12.50%)	0 / 22 (0.00%)	2 / 63 (3.17%)
occurrences all number	0	1	4	4	0	7
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 28 (3.57%)	0 / 21 (0.00%)	1 / 66 (1.52%)	0 / 32 (0.00%)	0 / 22 (0.00%)	5 / 63 (7.94%)
occurrences all number	1	0	1	0	0	5
Back Pain
subjects affected / exposed	2 / 28 (7.14%)	0 / 21 (0.00%)	6 / 66 (9.09%)	3 / 32 (9.38%)	1 / 22 (4.55%)	3 / 63 (4.76%)
occurrences all number	2	0	6	3	1	3
Musculoskeletal Pain
subjects affected / exposed	1 / 28 (3.57%)	0 / 21 (0.00%)	1 / 66 (1.52%)	3 / 32 (9.38%)	1 / 22 (4.55%)	0 / 63 (0.00%)
occurrences all number	1	0	1	3	1	0
Infections and infestations
Bronchitis
subjects affected / exposed	0 / 28 (0.00%)	0 / 21 (0.00%)	0 / 66 (0.00%)	0 / 32 (0.00%)	2 / 22 (9.09%)	2 / 63 (3.17%)
occurrences all number	0	0	0	0	2	2
Gastroenteritis
subjects affected / exposed	1 / 28 (3.57%)	0 / 21 (0.00%)	0 / 66 (0.00%)	2 / 32 (6.25%)	0 / 22 (0.00%)	2 / 63 (3.17%)
occurrences all number	1	0	0	2	0	4
Nasopharyngitis
subjects affected / exposed	1 / 28 (3.57%)	5 / 21 (23.81%)	8 / 66 (12.12%)	4 / 32 (12.50%)	4 / 22 (18.18%)	10 / 63 (15.87%)
occurrences all number	1	6	10	6	5	10
Pharyngitis
subjects affected / exposed	1 / 28 (3.57%)	1 / 21 (4.76%)	2 / 66 (3.03%)	2 / 32 (6.25%)	1 / 22 (4.55%)	1 / 63 (1.59%)
occurrences all number	1	1	2	2	1	1
Rhinitis
subjects affected / exposed	2 / 28 (7.14%)	0 / 21 (0.00%)	0 / 66 (0.00%)	2 / 32 (6.25%)	0 / 22 (0.00%)	1 / 63 (1.59%)
occurrences all number	3	0	0	2	0	2
Upper Respiratory Tract Infection
subjects affected / exposed	2 / 28 (7.14%)	0 / 21 (0.00%)	11 / 66 (16.67%)	5 / 32 (15.63%)	2 / 22 (9.09%)	4 / 63 (6.35%)
occurrences all number	2	0	21	6	3	8
Urinary Tract Infection
subjects affected / exposed	2 / 28 (7.14%)	0 / 21 (0.00%)	0 / 66 (0.00%)	0 / 32 (0.00%)	0 / 22 (0.00%)	0 / 63 (0.00%)
occurrences all number	5	0	0	0	0	0
Metabolism and nutrition disorders
Decreased Appetite
subjects affected / exposed	1 / 28 (3.57%)	1 / 21 (4.76%)	2 / 66 (3.03%)	1 / 32 (3.13%)	0 / 22 (0.00%)	4 / 63 (6.35%)
occurrences all number	1	1	2	1	0	6

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Were there any global substantial amendments to the protocol? Yes

18 Dec 2017

The overall reason for Amendment 1, considered a substantial protocol amendment and issued on 18 December 2017, was to incorporate Health Authority feedback regarding follow-up treatment and safety monitoring after the 24-week treatment period and hormonal contraceptive treatment.

06 Mar 2018

The overall reason for Amendment 2, considered a substantial protocol amendment and issued on 6 March 2018, was to implement the Health Authority recommendation to evaluate the effect of extended treatment on hepatitis B surface antigen (HBsAg) decline.

20 Feb 2019

The overall reasons for Amendment 4, considered a substantial protocol amendment and issued on 20 February 2019, were to implement an urgent safety measure based on DRC recommendations and also include a futility rule.

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: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels at Week 24

Primary: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels at Week 24

Primary: Posterior Probability of JNJ6379+NA over Placebo+NA for HBsAg Change from Baseline (log10) at Week 24 by Hepatitis B e Antigen Status for Currently not Treated Subjects

Primary: Posterior Probability of JNJ6379+NA over Placebo+NA for HBsAg Change from Baseline (log10) at Week 24 by Hepatitis B e Antigen Status for Currently not Treated Subjects

Primary: Posterior Probability of JNJ6379+NA over Placebo+NA for HBsAg Change from Baseline (log10) at Week 24 by Hepatitis B e Antigen Status for Virologically Suppressed Subjects

Primary: Posterior Probability of JNJ6379+NA over Placebo+NA for HBsAg Change from Baseline (log10) at Week 24 by Hepatitis B e Antigen Status for Virologically Suppressed Subjects

Secondary: Number of Subjects With Treatment- emergent Adverse Events (AEs)

Secondary: Number of Subjects With Treatment- emergent Adverse Events (AEs)

Secondary: Number of Subjects With Serious Adverse Events (SAEs)

Secondary: Number of Subjects With Serious Adverse Events (SAEs)

Secondary: Number of Subjects with Clinically Significant Changes in Vital Signs, Physical Examinations, Electrocardiogram (ECG), and Laboratory Findings

Secondary: Number of Subjects with Clinically Significant Changes in Vital Signs, Physical Examinations, Electrocardiogram (ECG), and Laboratory Findings

Secondary: Percentage of Subjects With HBsAg Levels Less Than (<) 1,000 or <100 International Units Per Milliliter (IU/mL) for Currently not Treated Subjects at Week 24

Secondary: Percentage of Subjects With HBsAg Levels Less Than (<) 1,000 or <100 International Units Per Milliliter (IU/mL) for Currently not Treated Subjects at Week 24

Secondary: Percentage of Subjects With HBsAg Levels Less Than (<) 1,000 or <100 International Units Per Milliliter (IU/mL) for Virologically Suppressed Subjects at Week 24

Secondary: Percentage of Subjects With HBsAg Levels Less Than (<) 1,000 or <100 International Units Per Milliliter (IU/mL) for Virologically Suppressed Subjects at Week 24

Secondary: Percentage of Subjects With Greater Than (>) 0.5 log10 IU/mL Reduction in HBsAg From Baseline for Currently-not Treated Subjects at Week 24

Secondary: Percentage of Subjects With Greater Than (>) 0.5 log10 IU/mL Reduction in HBsAg From Baseline for Currently-not Treated Subjects at Week 24

Secondary: Percentage of Subjects With Greater Than (>) 0.5 log10 IU/mL Reduction in HBsAg From Baseline for Virologically Suppressed Subjects at Week 24

Secondary: Percentage of Subjects With Greater Than (>) 0.5 log10 IU/mL Reduction in HBsAg From Baseline for Virologically Suppressed Subjects at Week 24

Secondary: Change From Baseline in Hepatitis B Virus (HBV) Deoxyribonucleic acid (DNA) Levels at Week 24 for Currently not Treated HbeAg Positive Subjects

Secondary: Change From Baseline in Hepatitis B Virus (HBV) Deoxyribonucleic acid (DNA) Levels at Week 24 for Currently not Treated HbeAg Positive Subjects

Secondary: Change From Baseline in Hepatitis B Virus (HBV) Deoxyribonucleic acid (DNA) Levels at Week 24 for Currently not Treated HbeAg Negative Subjects

Secondary: Change From Baseline in Hepatitis B Virus (HBV) Deoxyribonucleic acid (DNA) Levels at Week 24 for Currently not Treated HbeAg Negative Subjects

Secondary: Percentage of Subjects With Undetectable HBV DNA Levels at Week 24 for Currently not Treated Population

Secondary: Percentage of Subjects With Undetectable HBV DNA Levels at Week 24 for Currently not Treated Population

Secondary: Percentage of Subjects With Undetectable HBV DNA Levels at Week 24 for Virologically Suppressed Population

Secondary: Percentage of Subjects With Undetectable HBV DNA Levels at Week 24 for Virologically Suppressed Population

Secondary: Change From Baseline in Hepatitis B E Antigen (HBeAg) Levels for HBeAg Positive Subjects at Week 24

Secondary: Change From Baseline in Hepatitis B E Antigen (HBeAg) Levels for HBeAg Positive Subjects at Week 24

Secondary: Percentage of Subjects by HBeAg Levels Reduced from Baseline >0.5 log10 IU/mL and >1 log10 IU/mL for Currently not Treated Subjects at Week 24

Secondary: Percentage of Subjects by HBeAg Levels Reduced from Baseline >0.5 log10 IU/mL and >1 log10 IU/mL for Currently not Treated Subjects at Week 24

Secondary: Percentage of Subjects by HBeAg Levels Reduced from Baseline >0.5 log10 IU/mL and >1 log10 IU/mL for Virologically Suppressed Subjects at Week 24

Secondary: Percentage of Subjects by HBeAg Levels Reduced from Baseline >0.5 log10 IU/mL and >1 log10 IU/mL for Virologically Suppressed Subjects at Week 24

Secondary: Number of Subjects With HBsAg Seroclearance

Secondary: Number of Subjects With HBsAg Seroclearance

Secondary: Number of Subjects With HBsAg Seroconversion

Secondary: Number of Subjects With HBsAg Seroconversion

Secondary: Percentage of Subjects With Normalized Alanine Aminotransferase (ALT) Levels for Currently not Treated Population at Week 24

Secondary: Percentage of Subjects With Normalized Alanine Aminotransferase (ALT) Levels for Currently not Treated Population at Week 24

Secondary: Percentage of Subjects With Normalized Alanine Aminotransferase (ALT) Levels for Virologically Suppressed Population at Week 24

Secondary: Percentage of Subjects With Normalized Alanine Aminotransferase (ALT) Levels for Virologically Suppressed Population at Week 24

Secondary: Number of Subjects With Virological Breakthrough

Secondary: Number of Subjects With Virological Breakthrough

Secondary: Plasma Concentrations of Entecavir [ETV]

Secondary: Plasma Concentrations of Entecavir [ETV]

Secondary: Plasma Concentrations of Tenofovir (TFV) for Currently not Treated and Virologically Suppressed Population

Secondary: Plasma Concentrations of Tenofovir (TFV) for Currently not Treated and Virologically Suppressed Population

Secondary: Plasma Concentrations of JNJ-56136379 for Currently not Treated and Virologically Suppressed Population

Secondary: Plasma Concentrations of JNJ-56136379 for Currently not Treated and Virologically Suppressed Population

Secondary: Number of Subjects With Treatment-Associated Mutations

Secondary: Number of Subjects With Treatment-Associated Mutations

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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