Trial Outcomes & Findings for Entecavir Plus Tenofovir Combination Therapy Versus Entecavir Monotherapy in Naive Subjects With Chronic Hepatitis B (NCT NCT00410072)

Last Updated: 2013-03-15

Results Overview

HBV DNA levels \<50 IU/mL=approximately 300 copies/mL. Analyses of binary efficacy endpoint during on-treatment period focused on participants who received treatment and used the analysis of noncompleter=failure (NC=F). All participants who received treatment were included in the denominator, and participants with missing measurements were counted as nonresponders for the specific endpoints.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

669 participants

Primary outcome timeframe

At Week 96

Results posted on

2013-03-15

Participant Flow

669 participants were enrolled; 384 were randomized. Among 285 who were not randomized, 266 did not meet the study criteria, 11 other, 1 poor compliance/noncompliance, 4 lost to follow-up, 1 withdrew consent, and 2 for administrative reasons.

Participant milestones

Participant milestones
Measure	ETV 0.5 mg Entecavir (ETV) 0.5 mg monotherapy given once daily (QD) for 100 weeks	ETV 0.5 mg +TDF 300 mg ETV 0.5 mg plus Tenofovir (TDF) 300 mg combination therapy given QD for 100 weeks
Day 1 to Week 48 STARTED	182	197
Day 1 to Week 48 COMPLETED	176	185
Day 1 to Week 48 NOT COMPLETED	6	12
After Week 48 to Week 96 STARTED	176	185
After Week 48 to Week 96 COMPLETED	170	174
After Week 48 to Week 96 NOT COMPLETED	6	11

Reasons for withdrawal

Reasons for withdrawal
Measure	ETV 0.5 mg Entecavir (ETV) 0.5 mg monotherapy given once daily (QD) for 100 weeks	ETV 0.5 mg +TDF 300 mg ETV 0.5 mg plus Tenofovir (TDF) 300 mg combination therapy given QD for 100 weeks
Day 1 to Week 48 Adverse Event	1	2
Day 1 to Week 48 Lost to Follow-up	5	2
Day 1 to Week 48 Other	0	1
Day 1 to Week 48 poor compliance/noncompliance	0	3
Day 1 to Week 48 Pregnancy	0	2
Day 1 to Week 48 Withdrawal by Subject	0	2
After Week 48 to Week 96 Adverse Event	1	2
After Week 48 to Week 96 Death	0	1
After Week 48 to Week 96 Lack of Efficacy	1	0
After Week 48 to Week 96 Lost to Follow-up	2	4
After Week 48 to Week 96 Other	2	0
After Week 48 to Week 96 Poor compliance/noncompliance	0	1
After Week 48 to Week 96 Pregnancy	0	2
After Week 48 to Week 96 Withdrawal by Subject	0	1

Baseline Characteristics

Entecavir Plus Tenofovir Combination Therapy Versus Entecavir Monotherapy in Naive Subjects With Chronic Hepatitis B

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ETV 0.5 mg n=182 Participants Entecavir (ETV) 0.5 mg monotherapy given once daily (QD) for 100 weeks	ETV 0.5 mg +TDF 300 mg n=197 Participants ETV 0.5 mg plus Tenofovir (TDF) 300 mg combination therapy given QD for 100 weeks	Total n=379 Participants Total of all reporting groups
Age, Customized 16 - 20 years	13 Participants n=5 Participants	19 Participants n=7 Participants	32 Participants n=5 Participants
Age, Customized 21 - 64 years	157 Participants n=5 Participants	169 Participants n=7 Participants	326 Participants n=5 Participants
Age, Customized >=65 years	12 Participants n=5 Participants	9 Participants n=7 Participants	21 Participants n=5 Participants
Sex: Female, Male Female	66 Participants n=5 Participants	51 Participants n=7 Participants	117 Participants n=5 Participants
Sex: Female, Male Male	116 Participants n=5 Participants	146 Participants n=7 Participants	262 Participants n=5 Participants
Race/Ethnicity, Customized Asian	84 Participants n=5 Participants	102 Participants n=7 Participants	186 Participants n=5 Participants
Race/Ethnicity, Customized Black/African American	10 Participants n=5 Participants	4 Participants n=7 Participants	14 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian/Other Pacific Islander	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White	83 Participants n=5 Participants	87 Participants n=7 Participants	170 Participants n=5 Participants
Race/Ethnicity, Customized Other	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Country United States	35 participants n=5 Participants	43 participants n=7 Participants	78 participants n=5 Participants
Country Turkey	11 participants n=5 Participants	11 participants n=7 Participants	22 participants n=5 Participants
Country Russian Federation	24 participants n=5 Participants	23 participants n=7 Participants	47 participants n=5 Participants
Country Italy	12 participants n=5 Participants	15 participants n=7 Participants	27 participants n=5 Participants
Country India	5 participants n=5 Participants	9 participants n=7 Participants	14 participants n=5 Participants
Country France	8 participants n=5 Participants	5 participants n=7 Participants	13 participants n=5 Participants
Country Canada	29 participants n=5 Participants	33 participants n=7 Participants	62 participants n=5 Participants
Country Argentina	12 participants n=5 Participants	15 participants n=7 Participants	27 participants n=5 Participants
Country Poland	15 participants n=5 Participants	13 participants n=7 Participants	28 participants n=5 Participants
Country Brazil	5 participants n=5 Participants	3 participants n=7 Participants	8 participants n=5 Participants
Country Australia	24 participants n=5 Participants	24 participants n=7 Participants	48 participants n=5 Participants
Country South Africa	2 participants n=5 Participants	3 participants n=7 Participants	5 participants n=5 Participants
Region Africa	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Region Asia	29 Participants n=5 Participants	33 Participants n=7 Participants	62 Participants n=5 Participants
Region Europe	70 Participants n=5 Participants	67 Participants n=7 Participants	137 Participants n=5 Participants
Region North America	64 Participants n=5 Participants	76 Participants n=7 Participants	140 Participants n=5 Participants
Region South America	17 Participants n=5 Participants	18 Participants n=7 Participants	35 Participants n=5 Participants
Hepatitis B e antibody (HBeAb) at baseline Positive	60 Participants n=5 Participants	60 Participants n=7 Participants	120 Participants n=5 Participants
Hepatitis B e antibody (HBeAb) at baseline Negative	122 Participants n=5 Participants	137 Participants n=7 Participants	259 Participants n=5 Participants
Hepatitis B e antigen (HBeAg) status at baseline Positive (> 172,000 IU/mL; approx 10^6 copies/mL)	126 Participants n=5 Participants	138 Participants n=7 Participants	264 Participants n=5 Participants
Hepatitis B e antigen (HBeAg) status at baseline Negative (> 17,200 IU/mL; approx 10^5 copies/mL)	56 Participants n=5 Participants	59 Participants n=7 Participants	115 Participants n=5 Participants
Hepatitis B surface antigen (HBsAg) status at baseline Positive	182 Participants n=5 Participants	196 Participants n=7 Participants	378 Participants n=5 Participants
Hepatitis B surface antigen (HBsAg) status at baseline Negative	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: At Week 96

Population: Evaluable participants. A participant missing the efficacy assessments for a visit is considered a failure and is counted as evaluable.

Outcome measures

Outcome measures
Measure	ETV 0.5 mg n=182 Participants Entecavir (ETV) 0.5 mg monotherapy given once daily (QD) for 100 weeks	ETV 0.5 mg +TDF 300 mg n=197 Participants ETV 0.5 mg plus Tenofovir (TDF) 300 mg combination therapy given QD for 100 weeks
Percentage of Participants Who Achieved Hepatitis B Virus DNA (HBV DNA) Levels <50 IU/mL by Polymerase Chain Reaction (PCR) at Week 96	76.4 Percentage of participants	83.2 Percentage of participants

SECONDARY outcome

Timeframe: At Weeks 48 and 96

Population: Evaluable participants. If a participant is missing the efficacy assessments for a visit, this is considered a failure and is counted as evaluable.

Outcome measures

Outcome measures
Measure	ETV 0.5 mg n=182 Participants Entecavir (ETV) 0.5 mg monotherapy given once daily (QD) for 100 weeks	ETV 0.5 mg +TDF 300 mg n=197 Participants ETV 0.5 mg plus Tenofovir (TDF) 300 mg combination therapy given QD for 100 weeks
Percentage of Participants Who Achieved HBV DNA Levels <50 IU/mL by PCR at Week 48 and Week 96 by Hepatitis B e Antigen (HBeAg) Status HBeAg+ at Week 48 (n=126, n=138)	61.1 Percentage of participants	74.6 Percentage of participants
Percentage of Participants Who Achieved HBV DNA Levels <50 IU/mL by PCR at Week 48 and Week 96 by Hepatitis B e Antigen (HBeAg) Status HBeAg- at Week 48 (n=56, n=59)	91.1 Percentage of participants	93.2 Percentage of participants
Percentage of Participants Who Achieved HBV DNA Levels <50 IU/mL by PCR at Week 48 and Week 96 by Hepatitis B e Antigen (HBeAg) Status HBeAg+ at Week 96 (n=126, n=138)	69.8 Percentage of participants	80.4 Percentage of participants
Percentage of Participants Who Achieved HBV DNA Levels <50 IU/mL by PCR at Week 48 and Week 96 by Hepatitis B e Antigen (HBeAg) Status HBeAg- at Week 96 (n=56, n=59)	91.1 Percentage of participants	89.8 Percentage of participants

SECONDARY outcome

Timeframe: At Weeks 48 and 96

Population: Evaluable participants. A participant missing the efficacy assessments for a visit is considered a failure and is counted as evaluable.

LOQ=lower limit of quantitation. LOQ=29 IU/mL, or approximately 169 copies/mL. LOQ is the level above which quantitative results may be obtained with a specified degree of confidence. The LOQ is mathematically defined as equal to 10 times the standard deviation of the results for a series of replicates used to determine a justifiable limit of detection. Limits of quantitation are matrix-, method-, and analyte-specific.Analyses of binary efficacy endpoint during on-treatment period focused on participants who received treatment and used the analysis of noncompleter=failure (NC=F). All participants who received treatment were included in the denominator, and participants with missing measurements were counted as nonresponders for the specific endpoints.

Outcome measures

Outcome measures
Measure	ETV 0.5 mg n=182 Participants Entecavir (ETV) 0.5 mg monotherapy given once daily (QD) for 100 weeks	ETV 0.5 mg +TDF 300 mg n=197 Participants ETV 0.5 mg plus Tenofovir (TDF) 300 mg combination therapy given QD for 100 weeks
Percentage of Participants Who Achieved HBV DNA Levels <LOQ by PCR at Weeks 48 and 96 Overall at Week 48	67.6 Percentage of participants	74.6 Percentage of participants
Percentage of Participants Who Achieved HBV DNA Levels <LOQ by PCR at Weeks 48 and 96 Overall at Week 96	74.7 Percentage of participants	81.7 Percentage of participants

SECONDARY outcome

Timeframe: At Weeks 48 and 96

Population: Evaluable participants. A participant missing the efficacy assessments for a visit is considered a failure and is counted as evaluable.

LOD=Lower limit of detection. LOD) LOD=10 IU/mL, or approximately 58 copies/mL. LOD is the lowest concentration level that can be determined to be statistically different from a blank (99% confidence). The LOD is typically determined to be in the region where the signal to noise ratio is greater than 5. Limits of detection are matrix-, method-, and analyte-specific.Analyses of binary efficacy endpoint during on-treatment period focused on participants who received treatment and used the analysis of noncompleter=failure (NC=F). All participants who received treatment were included in the denominator, and participants with missing measurements were counted as nonresponders for the specific endpoints.

Outcome measures

Outcome measures
Measure	ETV 0.5 mg n=182 Participants Entecavir (ETV) 0.5 mg monotherapy given once daily (QD) for 100 weeks	ETV 0.5 mg +TDF 300 mg n=197 Participants ETV 0.5 mg plus Tenofovir (TDF) 300 mg combination therapy given QD for 100 weeks
Percentage of Participants Who Achieved HBV DNA Levels <LOD by PCR at Weeks 48 and 96 Overall at Week 48	58.2 Percentage of participants	66.0 Percentage of participants
Percentage of Participants Who Achieved HBV DNA Levels <LOD by PCR at Weeks 48 and 96 Overall at Week 96	68.1 Percentage of participants	76.6 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Weeks 48 and 96

Population: Evaluable participants at given time point. If a participant is missing the efficacy assessments for a visit, this is considered a failure and is counted as evaluable.

HBV DNA was analyzed by PCR, using the Roche COBAS®TaqMan - HPS assay. Reduction in Log 10 HBV count=reduced viral load.

Outcome measures

Outcome measures
Measure	ETV 0.5 mg n=182 Participants Entecavir (ETV) 0.5 mg monotherapy given once daily (QD) for 100 weeks	ETV 0.5 mg +TDF 300 mg n=197 Participants ETV 0.5 mg plus Tenofovir (TDF) 300 mg combination therapy given QD for 100 weeks
Mean Log 10 HBV DNA at Weeks 48 and 96 Baseline (n=182, 197)	7.48 log10 copies/mL Standard Error 0.109	7.53 log10 copies/mL Standard Error 0.100
Mean Log 10 HBV DNA at Weeks 48 and 96 Overall at Week 48 (n=176, 180)	1.88 log10 copies/mL Standard Error 0.065	1.56 log10 copies/mL Standard Error 0.026
Mean Log 10 HBV DNA at Weeks 48 and 96 Overall at Week 96 (n=165, 170)	1.68 log10 copies/mL Standard Error 0.048	1.51 log10 copies/mL Standard Error 0.038

SECONDARY outcome

Timeframe: At Weeks 48 and 96

Population: Evaluable participants. A participant missing the efficacy assessments for a visit is considered a failure and counted as evaluable.

ALT normalization= ≤1\*upper limit of normal (ULN). Analyses of binary efficacy endpoint during on-treatment period focused on participants who received treatment and used the analysis of noncompleter=failure (NC=F). All participants who received treatment were included in the denominator, and participants with missing measurements were counted as nonresponders for the specific endpoints.

Outcome measures

Outcome measures
Measure	ETV 0.5 mg n=182 Participants Entecavir (ETV) 0.5 mg monotherapy given once daily (QD) for 100 weeks	ETV 0.5 mg +TDF 300 mg n=197 Participants ETV 0.5 mg plus Tenofovir (TDF) 300 mg combination therapy given QD for 100 weeks
Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 48 and 96 Overall at Week 96	81.9 Percentage of participants	68.0 Percentage of participants
Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 48 and 96 Overall at Week 48	83.0 Percentage of participants	72.6 Percentage of participants

SECONDARY outcome

Timeframe: At Weeks 48 and 96

Population: Treated HBeAg-positive participants. If a participant was missing the efficacy assessments for a visit, this is considered a failure and was counted as evaluable.

HBeAg is a hepatitis B viral protein and is an indicator of active viral replication. Analyses of binary efficacy endpoint during on-treatment period focused on participants who received treatment and used the analysis of noncompleter=failure (NC=F). All participants who received treatment were included in the denominator, and participants with missing measurements were counted as nonresponders for the specific endpoints.

Outcome measures

Outcome measures
Measure	ETV 0.5 mg n=126 Participants Entecavir (ETV) 0.5 mg monotherapy given once daily (QD) for 100 weeks	ETV 0.5 mg +TDF 300 mg n=138 Participants ETV 0.5 mg plus Tenofovir (TDF) 300 mg combination therapy given QD for 100 weeks
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 48 and 96 Week 48	25.4 Percentage of participants	19.6 Percentage of participants
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 48 and 96 Week 96	3.97 Percentage of participants	29.7 Percentage of participants

SECONDARY outcome

Timeframe: At Weeks 48 and 96

Population: Treated HBeAg-positive participants. A participant missing the efficacy assessments for a visit was considered a failure and was counted as evaluable.

HBeAg seroconversion=HBeAg loss and presence of hepatitis B e antibody (HBeAb). HBeAg is a hepatitis B viral protein and is an indicator of active viral replication.

Outcome measures

Outcome measures
Measure	ETV 0.5 mg n=126 Participants Entecavir (ETV) 0.5 mg monotherapy given once daily (QD) for 100 weeks	ETV 0.5 mg +TDF 300 mg n=138 Participants ETV 0.5 mg plus Tenofovir (TDF) 300 mg combination therapy given QD for 100 weeks
Percentage of Participants With HBeAg Seroconversion [( at Weeks 48 and 96 Week 48	22.2 Percentage of participants	18.1 Percentage of participants
Percentage of Participants With HBeAg Seroconversion [( at Weeks 48 and 96 Week 96	32.5 Percentage of participants	21.7 Percentage of participants

SECONDARY outcome

Timeframe: At Weeks 48 and 96

Population: Treated HBeAg-positive participants. If a participant was missing the efficacy assessments for a visit, this is considered a failure and was counted as evaluable.

HBsAg = A part of the hepatitis B virus. When found in the blood, HBsAg is an early marker of infection. Analyses of binary efficacy endpoint during on-treatment period focused on participants who received treatment and used the analysis of noncompleter=failure (NC=F). All participants who received treatment were included in the denominator, and participants with missing measurements were counted as nonresponders for the specific endpoints.

Outcome measures

Outcome measures
Measure	ETV 0.5 mg n=126 Participants Entecavir (ETV) 0.5 mg monotherapy given once daily (QD) for 100 weeks	ETV 0.5 mg +TDF 300 mg n=138 Participants ETV 0.5 mg plus Tenofovir (TDF) 300 mg combination therapy given QD for 100 weeks
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48 and 96 Week 48	3.2 Percent of participants	1.4 Percent of participants
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48 and 96 Week 96	4.0 Percent of participants	5.1 Percent of participants

SECONDARY outcome

Timeframe: At Weeks 48 and 96

Population: Treated HBeAg-positive participants. If a participant was missing the efficacy assessments for a visit, this is considered a failure and was counted as evaluable.

HBsAg = a part of the hepatitis B virus that, when in the blood, is an early marker of infection.

Outcome measures

Outcome measures
Measure	ETV 0.5 mg n=126 Participants Entecavir (ETV) 0.5 mg monotherapy given once daily (QD) for 100 weeks	ETV 0.5 mg +TDF 300 mg n=138 Participants ETV 0.5 mg plus Tenofovir (TDF) 300 mg combination therapy given QD for 100 weeks
Percentage of Participants With HBsAg Seroconversion at Weeks 48 and 96 Week 48	0.8 Percentage of participants	0.7 Percentage of participants
Percentage of Participants With HBsAg Seroconversion at Weeks 48 and 96 Week 96	1.6 Percentage of participants	2.9 Percentage of participants

SECONDARY outcome

Timeframe: At Weeks 48 and 96

Population: All treated participants.

Using the Roche COBAS TaqMan - HPS assay. Lower limit of Quantitation (LOQ) is the level above which quantitative results may be obtained with a specified degree of confidence. The LOQ is mathematically defined as equal to 10 times the standard deviation of the results for a series of replicates used to determine a justifiable limit of detection. Limits of quantitation are matrix-, method-, and analyte-specific.

Outcome measures

Outcome measures
Measure	ETV 0.5 mg n=182 Participants Entecavir (ETV) 0.5 mg monotherapy given once daily (QD) for 100 weeks	ETV 0.5 mg +TDF 300 mg n=197 Participants ETV 0.5 mg plus Tenofovir (TDF) 300 mg combination therapy given QD for 100 weeks
Number of Participants With HBV DNA in Relevant Categories at Weeks 48 and 96 Missing at Week 96	9.3 Percentage of participants	13.7 Percentage of participants
Number of Participants With HBV DNA in Relevant Categories at Weeks 48 and 96 < LOQ (29 IU/mL) at Week 48	67.6 Percentage of participants	74.6 Percentage of participants
Number of Participants With HBV DNA in Relevant Categories at Weeks 48 and 96 LOQ - <50 IU/mL at Week 48	2.7 Percentage of participants	5.6 Percentage of participants
Number of Participants With HBV DNA in Relevant Categories at Weeks 48 and 96 50 - <172 IU/mL at Week 48	7.1 Percentage of participants	6.6 Percentage of participants
Number of Participants With HBV DNA in Relevant Categories at Weeks 48 and 96 172 - <1720 IU/mL at Week 48	7.7 Percentage of participants	4.1 Percentage of participants
Number of Participants With HBV DNA in Relevant Categories at Weeks 48 and 96 1720 - <17,200 IU/mL at Week 48	9.3 Percentage of participants	0.5 Percentage of participants
Number of Participants With HBV DNA in Relevant Categories at Weeks 48 and 96 17,200 - <172,000 IU/mL at Week 48	1.6 Percentage of participants	0 Percentage of participants
Number of Participants With HBV DNA in Relevant Categories at Weeks 48 and 96 ≥172,000 IU/mL at Week 48	0.5 Percentage of participants	0 Percentage of participants
Number of Participants With HBV DNA in Relevant Categories at Weeks 48 and 96 Missing at Week 48	3.3 Percentage of participants	8.6 Percentage of participants
Number of Participants With HBV DNA in Relevant Categories at Weeks 48 and 96 < LOQ (29 IU/mL) at Week 96	74.7 Percentage of participants	81.7 Percentage of participants
Number of Participants With HBV DNA in Relevant Categories at Weeks 48 and 96 LOQ - <50 IU/mL at Week 96	1.6 Percentage of participants	1.5 Percentage of participants
Number of Participants With HBV DNA in Relevant Categories at Weeks 48 and 96 50 - <172 IU/mL at Week 96	3.3 Percentage of participants	1.0 Percentage of participants
Number of Participants With HBV DNA in Relevant Categories at Weeks 48 and 96 172 - <1720 IU/mL at Week 96	5.5 Percentage of participants	1.5 Percentage of participants
Number of Participants With HBV DNA in Relevant Categories at Weeks 48 and 96 1720 - <17,200 IU/mL at Week 96	4.9 Percentage of participants	0 Percentage of participants
Number of Participants With HBV DNA in Relevant Categories at Weeks 48 and 96 17,200 - <172,000 IU/mL at Week 96	0.5 Percentage of participants	0 Percentage of participants
Number of Participants With HBV DNA in Relevant Categories at Weeks 48 and 96 ≥172,000 IU/mL at Week 96	0 Percentage of participants	0.5 Percentage of participants

SECONDARY outcome

Timeframe: From enrollment through Week 100 + 24-week follow-up

Population: All treated participants.

AE: any new untoward medical occurrence/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Participants who discontinued the study due to any AEs were recorded.

Outcome measures

Outcome measures
Measure	ETV 0.5 mg n=182 Participants Entecavir (ETV) 0.5 mg monotherapy given once daily (QD) for 100 weeks	ETV 0.5 mg +TDF 300 mg n=197 Participants ETV 0.5 mg plus Tenofovir (TDF) 300 mg combination therapy given QD for 100 weeks
Number of Participants With Adverse Events, Serious Adverse Events, and Discontinuations From Study Drug Due to Adverse Events or Laboratory Abnormalities Deaths	0 Participants	3 Participants
Number of Participants With Adverse Events, Serious Adverse Events, and Discontinuations From Study Drug Due to Adverse Events or Laboratory Abnormalities SAEs	12 Participants	14 Participants
Number of Participants With Adverse Events, Serious Adverse Events, and Discontinuations From Study Drug Due to Adverse Events or Laboratory Abnormalities Adverse events	132 Participants	131 Participants
Number of Participants With Adverse Events, Serious Adverse Events, and Discontinuations From Study Drug Due to Adverse Events or Laboratory Abnormalities Discontinuations due to AEs	2 Participants	5 Participants
Number of Participants With Adverse Events, Serious Adverse Events, and Discontinuations From Study Drug Due to Adverse Events or Laboratory Abnormalities Related AEs	39 Participants	49 Participants

SECONDARY outcome

Timeframe: Week 48

Population: All participants who received study drug and with HBV DNA levels \>=50 IU/mL

ETVr=entecavir resistance; TDFr=tenofovir resistance. HBV polymerase using the Trugene® HBV Genotyping Kit. HBV resistance: genotyping of HBV polymerase will be performed on stored viral samples at any timepoint when considered appropriate based on virologic response, including any specimen with detectable HBV DNA. When appropriate, phenotyping will also be used.

Outcome measures

Outcome measures
Measure	ETV 0.5 mg n=51 Participants Entecavir (ETV) 0.5 mg monotherapy given once daily (QD) for 100 weeks	ETV 0.5 mg +TDF 300 mg n=33 Participants ETV 0.5 mg plus Tenofovir (TDF) 300 mg combination therapy given QD for 100 weeks
Number of Participants With HBV Resistance Through Week 48 ETVr	0 Participants	0 Participants
Number of Participants With HBV Resistance Through Week 48 TDFr	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Week 96

Population: Participants who received study drug and with HBV DNA levels \>=50 IU/mL.

ETVr=entecavir resistance; TFDr=tenofovir resistance. HBV polymerase using the Trugene® HBV Genotyping Kit. HBV resistance: genotyping of HBV polymerase will be performed on stored viral samples at any timepoint when considered appropriate based on virologic response, including any specimen with detectable HBV DNA. When appropriate, phenotyping will also be used.

Outcome measures

Outcome measures
Measure	ETV 0.5 mg n=33 Participants Entecavir (ETV) 0.5 mg monotherapy given once daily (QD) for 100 weeks	ETV 0.5 mg +TDF 300 mg n=10 Participants ETV 0.5 mg plus Tenofovir (TDF) 300 mg combination therapy given QD for 100 weeks
Number of Participants With HBV Resistance at Week 96 ETVr	0 Participants	0 Participants
Number of Participants With HBV Resistance at Week 96 TDFr	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Week 48

Population: Participants with confirmed \>=1 log10 increase in HBV DNA from the on-treatment nadir

ETVr=entecavir resistance; TFDr=tenofovir resistance. Virologic breakthrough= confirmed \>= 1 log10 increase in HBV DNA from the on-treatment nadir

Outcome measures

Outcome measures
Measure	ETV 0.5 mg n=1 Participants Entecavir (ETV) 0.5 mg monotherapy given once daily (QD) for 100 weeks	ETV 0.5 mg +TDF 300 mg n=7 Participants ETV 0.5 mg plus Tenofovir (TDF) 300 mg combination therapy given QD for 100 weeks
Number of Participants With Virologic Breakthrough at Week 48 ETVr	0 Participants	0 Participants
Number of Participants With Virologic Breakthrough at Week 48 TDFr	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Week 96

Population: Participants with confirmed \>= 1 log10 increase in HBV DNA from moving nadir

ETVr=entecavir resistance; TFDr=tenofovir resistance. Virologic breakthrough=confirmed \>=1 log10 increase in HBV DNA from moving nadir

Outcome measures

Outcome measures
Measure	ETV 0.5 mg n=1 Participants Entecavir (ETV) 0.5 mg monotherapy given once daily (QD) for 100 weeks	ETV 0.5 mg +TDF 300 mg n=7 Participants ETV 0.5 mg plus Tenofovir (TDF) 300 mg combination therapy given QD for 100 weeks
Number of Participants With Virologic Breakthrough at Week 96 ETVr	0 Participants	0 Participants
Number of Participants With Virologic Breakthrough at Week 96 TDFr	0 Participants	0 Participants

Adverse Events

ETV 0.5 mg

Serious events: 13 serious events

Other events: 69 other events

Deaths: 0 deaths

ETV/TDF 0.5 mg +TDF 300 mg

Serious events: 14 serious events

Other events: 73 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	ETV 0.5 mg n=182 participants at risk ETV 0.5 mg monotherapy given QD for 100 weeks	ETV/TDF 0.5 mg +TDF 300 mg n=197 participants at risk ETV 0.5 mg plus TDF 300 mg combination therapy given once daily (QD) for 100 weeks
Musculoskeletal and connective tissue disorders BACK PAIN	7.1% 13/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	4.6% 9/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Gastrointestinal disorders DIARRHOEA	6.0% 11/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	6.6% 13/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Respiratory, thoracic and mediastinal disorders COUGH	3.8% 7/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	6.6% 13/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
General disorders FATIGUE	6.0% 11/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	6.1% 12/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Gastrointestinal disorders ABDOMINAL PAIN UPPER	7.1% 13/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	4.1% 8/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Nervous system disorders HEADACHE	10.4% 19/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	11.2% 22/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Gastrointestinal disorders NAUSEA	4.9% 9/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	10.2% 20/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Infections and infestations NASOPHARYNGITIS	6.0% 11/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	9.1% 18/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.

Additional Information

BMS Study Director

Bristol-Myers Squibb

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication
Publication restrictions are in place

Restriction type: OTHER

Measure	ETV 0.5 mg n=182 participants at risk ETV 0.5 mg monotherapy given QD for 100 weeks	ETV/TDF 0.5 mg +TDF 300 mg n=197 participants at risk ETV 0.5 mg plus TDF 300 mg combination therapy given once daily (QD) for 100 weeks
Psychiatric disorders ACUTE PSYCHOSIS	0.55% 1/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	0.00% 0/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Gastrointestinal disorders COLITIS ULCERATIVE	0.00% 0/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	0.51% 1/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Hepatobiliary disorders HEPATITIS	0.00% 0/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	0.51% 1/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Infections and infestations HEPATITIS A	0.00% 0/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	0.51% 1/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Reproductive system and breast disorders OVARIAN CYST	0.55% 1/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	0.00% 0/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Nervous system disorders CEREBRAL ISCHAEMIA	0.55% 1/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	0.00% 0/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Nervous system disorders CEREBROVASCULAR ACCIDENT	0.55% 1/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	0.00% 0/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) HEPATIC NEOPLASM MALIGNANT	1.6% 3/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	0.00% 0/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Gastrointestinal disorders OESOPHAGEAL VARICES HAEMORRHAGE	0.00% 0/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	0.51% 1/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Injury, poisoning and procedural complications ANKLE FRACTURE	0.00% 0/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	0.51% 1/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Cardiac disorders CARDIAC ARREST	0.00% 0/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	0.51% 1/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Gastrointestinal disorders GASTRIC ULCER HAEMORRHAGE	0.00% 0/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	0.51% 1/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Injury, poisoning and procedural complications HAND FRACTURE	0.00% 0/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	0.51% 1/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Infections and infestations HEPATITIS B	0.00% 0/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	0.51% 1/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Injury, poisoning and procedural complications TRAUMATIC BRAIN INJURY	0.00% 0/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	1.0% 2/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Hepatobiliary disorders CHOLELITHIASIS	0.55% 1/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	0.00% 0/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Metabolism and nutrition disorders DIABETIC COMPLICATION	0.55% 1/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	0.00% 0/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) BREAST CANCER	0.00% 0/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	0.51% 1/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Gastrointestinal disorders PEPTIC ULCER	0.00% 0/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	0.51% 1/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Infections and infestations ACUTE SINUSITIS	0.00% 0/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	0.51% 1/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Investigations BLOOD AMYLASE INCREASED	0.55% 1/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	0.00% 0/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) GASTRIC CANCER	0.55% 1/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	0.00% 0/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Vascular disorders RAYNAUD'S PHENOMENON	0.55% 1/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	0.00% 0/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Musculoskeletal and connective tissue disorders SPINAL OSTEOARTHRITIS	0.00% 0/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	0.51% 1/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Gastrointestinal disorders DIVERTICULUM INTESTINAL HAEMORRHAGIC	0.55% 1/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	0.00% 0/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Gastrointestinal disorders GASTRIC ULCER	0.00% 0/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	0.51% 1/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Gastrointestinal disorders HAEMORRHOIDS	0.55% 1/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	0.00% 0/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) HEPATIC NEOPLASM	0.00% 0/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	0.51% 1/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Nervous system disorders ISCHAEMIC STROKE	0.55% 1/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	0.00% 0/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.
Nervous system disorders SUBARACHNOID HAEMORRHAGE	0.55% 1/182 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.	0.00% 0/197 • Week 0 to Week 100 (on study), Post-dosing follow-up - 24 Weeks Participants who have study medication completed or discontinued permanently were followed for 24 weeks post-dosing for safety.