Trial Outcomes & Findings for Safety and Efficacy of GS-4774 for the Treatment of Chronic Hepatitis B (NCT NCT01943799)

NCT ID: NCT01943799

Last Updated: 2019-11-01

Results Overview

The change from baseline to Week 24 in HBsAg was analyzed using a mixed effect model for repeated measures (MMRM). The model included included treatment, HBsAg baseline level (≤ 1000 IU/mL or \> 1000 IU/mL), HBeAg baseline status (positive or negative), visit, and treatment-by-visit interaction as fixed effects and visit as a repeated measure.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

178 participants

Primary outcome timeframe

Baseline; Week 24

Results posted on

2019-11-01

Participant Flow

Participants were enrolled at study sites in United States and New Zealand. The first participant was screened on 13 September 2013. The last study visit occurred on 03 March 2015.

213 participants were screened.

Participant milestones

Participant milestones
Measure	OAV Alone (Group A) Participants continued to receive their prebaseline oral antiviral (OAV) regimen alone from baseline to Week 48. Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 2 YU (Group B) Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 2 yeast units (YU) administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 10 YU (Group C) Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 10 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 40 YU (Group D) Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 40 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.
Overall Study STARTED	27	50	51	50
Overall Study COMPLETED	22	47	49	50
Overall Study NOT COMPLETED	5	3	2	0

Reasons for withdrawal

Reasons for withdrawal
Measure	OAV Alone (Group A) Participants continued to receive their prebaseline oral antiviral (OAV) regimen alone from baseline to Week 48. Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 2 YU (Group B) Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 2 yeast units (YU) administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 10 YU (Group C) Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 10 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.
Overall Study Lost to Follow-up	0	1	1
Overall Study Protocol Violation	1	0	0
Overall Study Withdrawal by Subject	4	2	1

Baseline Characteristics

1 participant from the United States was randomized to OAV + GS-4774 2 YU but received OAV + GS-4774 10 YU.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	OAV Alone (Group A) n=27 Participants Participants continued to receive their prebaseline OAV regimen alone from baseline to Week 48. Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 2 YU (Group B) n=50 Participants Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 2 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 10 YU (Group C) n=51 Participants Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 10 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 40 YU (Group D) n=50 Participants Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 40 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	Total n=178 Participants Total of all reporting groups
Age, Continuous	45 years STANDARD_DEVIATION 10.9 • n=5 Participants	50 years STANDARD_DEVIATION 9.0 • n=7 Participants	47 years STANDARD_DEVIATION 10.0 • n=5 Participants	47 years STANDARD_DEVIATION 11.1 • n=4 Participants	47 years STANDARD_DEVIATION 10.2 • n=21 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	16 Participants n=7 Participants	14 Participants n=5 Participants	19 Participants n=4 Participants	56 Participants n=21 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	34 Participants n=7 Participants	37 Participants n=5 Participants	31 Participants n=4 Participants	122 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	4 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	27 Participants n=5 Participants	48 Participants n=7 Participants	50 Participants n=5 Participants	49 Participants n=4 Participants	174 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race/Ethnicity, Customized Asian	21 Participants n=5 Participants	40 Participants n=7 Participants	41 Participants n=5 Participants	34 Participants n=4 Participants	136 Participants n=21 Participants
Race/Ethnicity, Customized White	5 Participants n=5 Participants	6 Participants n=7 Participants	3 Participants n=5 Participants	7 Participants n=4 Participants	21 Participants n=21 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	2 Participants n=4 Participants	10 Participants n=21 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants	8 Participants n=21 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Region of Enrollment New Zealand	4 Participants n=5 Participants • 1 participant from the United States was randomized to OAV + GS-4774 2 YU but received OAV + GS-4774 10 YU.	6 Participants n=7 Participants • 1 participant from the United States was randomized to OAV + GS-4774 2 YU but received OAV + GS-4774 10 YU.	2 Participants n=5 Participants • 1 participant from the United States was randomized to OAV + GS-4774 2 YU but received OAV + GS-4774 10 YU.	7 Participants n=4 Participants • 1 participant from the United States was randomized to OAV + GS-4774 2 YU but received OAV + GS-4774 10 YU.	19 Participants n=21 Participants • 1 participant from the United States was randomized to OAV + GS-4774 2 YU but received OAV + GS-4774 10 YU.
Region of Enrollment United States	23 Participants n=5 Participants • 1 participant from the United States was randomized to OAV + GS-4774 2 YU but received OAV + GS-4774 10 YU.	44 Participants n=7 Participants • 1 participant from the United States was randomized to OAV + GS-4774 2 YU but received OAV + GS-4774 10 YU.	49 Participants n=5 Participants • 1 participant from the United States was randomized to OAV + GS-4774 2 YU but received OAV + GS-4774 10 YU.	43 Participants n=4 Participants • 1 participant from the United States was randomized to OAV + GS-4774 2 YU but received OAV + GS-4774 10 YU.	159 Participants n=21 Participants • 1 participant from the United States was randomized to OAV + GS-4774 2 YU but received OAV + GS-4774 10 YU.
Hepatitis B Surface Antigen (HBsAg) (log10 IU/mL)	2.5 log10 IU/mL STANDARD_DEVIATION 1.46 • n=5 Participants	3.1 log10 IU/mL STANDARD_DEVIATION 0.72 • n=7 Participants	3.0 log10 IU/mL STANDARD_DEVIATION 1.02 • n=5 Participants	3.0 log10 IU/mL STANDARD_DEVIATION 0.86 • n=4 Participants	2.9 log10 IU/mL STANDARD_DEVIATION 0.99 • n=21 Participants
HBsAg Level ≤ 1000 IU/mL	13 Participants n=5 Participants	18 Participants n=7 Participants	21 Participants n=5 Participants	21 Participants n=4 Participants	73 Participants n=21 Participants
HBsAg Level > 1000 IU/mL	14 Participants n=5 Participants	32 Participants n=7 Participants	30 Participants n=5 Participants	29 Participants n=4 Participants	105 Participants n=21 Participants
Hepatitis B Envelope Antigen (HBeAg) Status Positive	7 Participants n=5 Participants	13 Participants n=7 Participants	12 Participants n=5 Participants	12 Participants n=4 Participants	44 Participants n=21 Participants
Hepatitis B Envelope Antigen (HBeAg) Status Negative	20 Participants n=5 Participants	37 Participants n=7 Participants	39 Participants n=5 Participants	38 Participants n=4 Participants	134 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline; Week 24

Population: Participants in the Full Analysis Set (participants who were randomized and had a Baseline/Day 1 visit for Treatment Group A or have received at least 1 dose of GS-4774 for Treatment Group B, C, and D) with available data were analyzed. Participants were analyzed according to the randomized treatment assignment.

Outcome measures

Outcome measures
Measure	OAV Alone (Group A) n=21 Participants Participants continued to receive their prebaseline OAV regimen alone from baseline to Week 48. Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 2 YU (Group B) n=47 Participants Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 2 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 10 YU (Group C) n=48 Participants Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 10 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 40 YU (Group D) n=49 Participants Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 40 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.
Change From Baseline in HBsAg at Week 24	-0.019 log10 IU/mL Interval -0.07 to 0.031	-0.020 log10 IU/mL Interval -0.055 to 0.014	-0.026 log10 IU/mL Interval -0.06 to 0.008	-0.048 log10 IU/mL Interval -0.082 to -0.014

SECONDARY outcome

Timeframe: Baseline; Week 12

Population: Participants in the Full Analysis Set with available data were analyzed.

The change from baseline to Week 12 in HBsAg was analyzed using a MMRM. The model included included treatment, HBsAg baseline level (≤ 1000 IU/mL or \> 1000 IU/mL), HBeAg baseline status (positive or negative), visit, and treatment-by-visit interaction as fixed effects and visit as a repeated measure.

Outcome measures

Outcome measures
Measure	OAV Alone (Group A) n=21 Participants Participants continued to receive their prebaseline OAV regimen alone from baseline to Week 48. Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 2 YU (Group B) n=48 Participants Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 2 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 10 YU (Group C) n=49 Participants Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 10 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 40 YU (Group D) n=49 Participants Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 40 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.
Change From Baseline in HBsAg at Week 12	-0.004 log10 IU/mL Interval -0.041 to 0.033	-0.016 log10 IU/mL Interval -0.041 to 0.01	-0.017 log10 IU/mL Interval -0.043 to 0.008	-0.028 log10 IU/mL Interval -0.054 to -0.003

SECONDARY outcome

Timeframe: Baseline; Week 48

Population: Participants in the Full Analysis Set with available data were analyzed.

The change from baseline to Week 48 in HBsAg was analyzed using a MMRM. The model included included treatment, HBsAg baseline level (≤ 1000 IU/mL or \> 1000 IU/mL), HBeAg baseline status (positive or negative), visit, and treatment-by-visit interaction as fixed effects and visit as a repeated measure.

Outcome measures

Outcome measures
Measure	OAV Alone (Group A) n=20 Participants Participants continued to receive their prebaseline OAV regimen alone from baseline to Week 48. Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 2 YU (Group B) n=48 Participants Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 2 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 10 YU (Group C) n=48 Participants Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 10 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 40 YU (Group D) n=49 Participants Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 40 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.
Change From Baseline in HBsAg at Week 48	-0.043 log10 IU/mL Interval -0.179 to 0.094	-0.055 log10 IU/mL Interval -0.148 to 0.038	-0.051 log10 IU/mL Interval -0.143 to 0.041	-0.166 log10 IU/mL Interval -0.257 to -0.075

SECONDARY outcome

Timeframe: Week 24

Population: Participants in the Full Analysis Set with HBsAg Level above 0.066 IU/mL at Baseline were analyzed.

HBsAg loss was defined as HBsAg level decreasing from \>0.066 IU/mL at baseline to ≤ 0.066 IU/mL at any postbaseline visit. HBsAb seroconversion was defined as HBsAb level increasing from \< 12 mIU/mL at baseline to ≥ 12 mIU/mL at any postbaseline visit.

Outcome measures

Outcome measures
Measure	OAV Alone (Group A) n=25 Participants Participants continued to receive their prebaseline OAV regimen alone from baseline to Week 48. Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 2 YU (Group B) n=50 Participants Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 2 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 10 YU (Group C) n=50 Participants Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 10 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 40 YU (Group D) n=50 Participants Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 40 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.
Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 24 HBsAg Loss	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 24 HBsAg Loss and Seroconversion	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Week 48

Population: Participants in the Full Analysis Set with HBsAg Level above 0.066 IU/mL at Baseline were analyzed.

Outcome measures

Outcome measures
Measure	OAV Alone (Group A) n=25 Participants Participants continued to receive their prebaseline OAV regimen alone from baseline to Week 48. Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 2 YU (Group B) n=50 Participants Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 2 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 10 YU (Group C) n=50 Participants Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 10 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 40 YU (Group D) n=50 Participants Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 40 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.
Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 48 HBsAg Loss	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 48 HBsAg Loss and Seroconversion	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Week 24

Population: Participants in the Full Analysis Set with positive HBeAg at baseline were analyzed.

HBeAg loss was defined as a qualitative HBeAg result changing from positive at baseline to negative at any postbaseline visit. HBeAb seroconversion was defined as a qualitative HBeAb result changing from negative at baseline to positive at any postbaseline visit.

Outcome measures

Outcome measures
Measure	OAV Alone (Group A) n=7 Participants Participants continued to receive their prebaseline OAV regimen alone from baseline to Week 48. Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 2 YU (Group B) n=13 Participants Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 2 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 10 YU (Group C) n=12 Participants Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 10 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 40 YU (Group D) n=12 Participants Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 40 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.
Percentage of Participants With HBeAg Loss and HBeAg Seroconversion by Week 24 HBeAg Loss	0 percentage of participants	0 percentage of participants	25.0 percentage of participants	0 percentage of participants
Percentage of Participants With HBeAg Loss and HBeAg Seroconversion by Week 24 HBeAg Loss and Seroconversion	0 percentage of participants	0 percentage of participants	25.0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Week 48

Population: Participants in the Full Analysis Set with positive HBeAg at baseline were analyzed.

Outcome measures

Outcome measures
Measure	OAV Alone (Group A) n=7 Participants Participants continued to receive their prebaseline OAV regimen alone from baseline to Week 48. Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 2 YU (Group B) n=13 Participants Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 2 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 10 YU (Group C) n=12 Participants Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 10 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 40 YU (Group D) n=12 Participants Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 40 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.
Percentage of Participants With HBeAg Loss and HBeAg Seroconversion by Week 48 HBeAg Loss	0 percentage of participants	7.7 percentage of participants	33.3 percentage of participants	0 percentage of participants
Percentage of Participants With HBeAg Loss and HBeAg Seroconversion by Week 48 HBeAg Loss and Seroconversion	0 percentage of participants	7.7 percentage of participants	25.0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Baseline; Weeks 12, 24, and 48

Population: Participants in the Full Analysis Set were analyzed.

HBsAg 1-log decline was defined as ≥ 1 decline from baseline in log10 IU/mL serum HBsAg at any postbaseline visit within the targeted time window.

Outcome measures

Outcome measures
Measure	OAV Alone (Group A) n=27 Participants Participants continued to receive their prebaseline OAV regimen alone from baseline to Week 48. Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 2 YU (Group B) n=51 Participants Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 2 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 10 YU (Group C) n=50 Participants Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 10 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 40 YU (Group D) n=50 Participants Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 40 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.
Percentage of Participants With a 1-log Decline in HBsAg by Weeks 12, 24, and 48 ≥ 1 log10 IU/mL Decline at Week 12	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Percentage of Participants With a 1-log Decline in HBsAg by Weeks 12, 24, and 48 ≥ 1 log10 IU/mL Decline at Week 24	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Percentage of Participants With a 1-log Decline in HBsAg by Weeks 12, 24, and 48 ≥ 1 log10 IU/mL Decline at Week 48	0 percentage of participants	0 percentage of participants	0 percentage of participants	2.0 percentage of participants

Adverse Events

OAV Alone (Group A)

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

OAV + GS-4774 2 YU (Group B)

Serious events: 1 serious events

Other events: 39 other events

Deaths: 0 deaths

OAV + GS-4774 10 YU (Group C)

Serious events: 1 serious events

Other events: 47 other events

Deaths: 0 deaths

OAV + GS-4774 40 YU (Group D)

Serious events: 0 serious events

Other events: 46 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	OAV Alone (Group A) n=27 participants at risk Participants continued to receive their prebaseline OAV regimen alone from baseline to Week 48. Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 2 YU (Group B) n=50 participants at risk Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 2 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 10 YU (Group C) n=51 participants at risk Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 10 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.	OAV + GS-4774 40 YU (Group D) n=50 participants at risk Participants continued to receive their prebaseline OAV regimen from baseline to Week 48 and received GS-4774 40 YU administered via subcutaneous injection every 4 weeks for 20 weeks (total of 6 doses). Prebaseline OAV regimen may have included the following: tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination.
Infections and infestations Colonic abscess	0.00% 0/27 • First dose date up to Week 20 plus 28 days The Safety Analysis Set included participants who have had a Baseline/Day 1 visit for Group A or have received at least one dose of GS-4774 for Group B, C, and D. For each participant, the average of non-missing doses of GS-4774 were calculated. The participant was assigned to Group A if the average was 0, or Group B if the average was greater than 0 and no more than 6 YU, or Group C if the average was greater than 6 YU and no more than 25 YU, or Group D if the average was greater than 25 YU.	0.00% 0/50 • First dose date up to Week 20 plus 28 days The Safety Analysis Set included participants who have had a Baseline/Day 1 visit for Group A or have received at least one dose of GS-4774 for Group B, C, and D. For each participant, the average of non-missing doses of GS-4774 were calculated. The participant was assigned to Group A if the average was 0, or Group B if the average was greater than 0 and no more than 6 YU, or Group C if the average was greater than 6 YU and no more than 25 YU, or Group D if the average was greater than 25 YU.	2.0% 1/51 • First dose date up to Week 20 plus 28 days The Safety Analysis Set included participants who have had a Baseline/Day 1 visit for Group A or have received at least one dose of GS-4774 for Group B, C, and D. For each participant, the average of non-missing doses of GS-4774 were calculated. The participant was assigned to Group A if the average was 0, or Group B if the average was greater than 0 and no more than 6 YU, or Group C if the average was greater than 6 YU and no more than 25 YU, or Group D if the average was greater than 25 YU.	0.00% 0/50 • First dose date up to Week 20 plus 28 days The Safety Analysis Set included participants who have had a Baseline/Day 1 visit for Group A or have received at least one dose of GS-4774 for Group B, C, and D. For each participant, the average of non-missing doses of GS-4774 were calculated. The participant was assigned to Group A if the average was 0, or Group B if the average was greater than 0 and no more than 6 YU, or Group C if the average was greater than 6 YU and no more than 25 YU, or Group D if the average was greater than 25 YU.
Psychiatric disorders Suicide attempt	0.00% 0/27 • First dose date up to Week 20 plus 28 days The Safety Analysis Set included participants who have had a Baseline/Day 1 visit for Group A or have received at least one dose of GS-4774 for Group B, C, and D. For each participant, the average of non-missing doses of GS-4774 were calculated. The participant was assigned to Group A if the average was 0, or Group B if the average was greater than 0 and no more than 6 YU, or Group C if the average was greater than 6 YU and no more than 25 YU, or Group D if the average was greater than 25 YU.	2.0% 1/50 • First dose date up to Week 20 plus 28 days The Safety Analysis Set included participants who have had a Baseline/Day 1 visit for Group A or have received at least one dose of GS-4774 for Group B, C, and D. For each participant, the average of non-missing doses of GS-4774 were calculated. The participant was assigned to Group A if the average was 0, or Group B if the average was greater than 0 and no more than 6 YU, or Group C if the average was greater than 6 YU and no more than 25 YU, or Group D if the average was greater than 25 YU.	0.00% 0/51 • First dose date up to Week 20 plus 28 days The Safety Analysis Set included participants who have had a Baseline/Day 1 visit for Group A or have received at least one dose of GS-4774 for Group B, C, and D. For each participant, the average of non-missing doses of GS-4774 were calculated. The participant was assigned to Group A if the average was 0, or Group B if the average was greater than 0 and no more than 6 YU, or Group C if the average was greater than 6 YU and no more than 25 YU, or Group D if the average was greater than 25 YU.	0.00% 0/50 • First dose date up to Week 20 plus 28 days The Safety Analysis Set included participants who have had a Baseline/Day 1 visit for Group A or have received at least one dose of GS-4774 for Group B, C, and D. For each participant, the average of non-missing doses of GS-4774 were calculated. The participant was assigned to Group A if the average was 0, or Group B if the average was greater than 0 and no more than 6 YU, or Group C if the average was greater than 6 YU and no more than 25 YU, or Group D if the average was greater than 25 YU.

Other adverse events

Additional Information

Gilead Clinical Study Information Center

Gilead Sciences

Phone: 1-833-445-3230 (GILEAD-0)

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
Publication restrictions are in place

Restriction type: OTHER