Trial Outcomes & Findings for B-Enhancement of HBV Vaccination in Persons Living With HIV (BEe-HIVe): Evaluation of HEPLISAV-B (NCT NCT04193189)

NCT ID: NCT04193189

Last Updated: 2025-07-20

Results Overview

Primary seroprotection response was defined as antibody titer against hepatitis B surface antigen (anti-HBs) ≥10 mIU/mL at 8 weeks after 2-dose vaccination series and at 4 weeks after 3-dose vaccination series. If the completion of the vaccine series was delayed (a delay of ≤4 weeks was allowed), the trial protocol specified obtaining an antibody result at 8 weeks for the 2-dose series or at 4 weeks for the 3-dose series after vaccine completion for use in the primary outcome analysis. The study was designed separately for the two study populations (Groups A and B), and the analysis was conducted separately, as prespecified in the study protocol and Statistical Analysis Plan (SAP). In Group A, two-sided 97.5% confidence intervals (CI) were specified for the SPR differences between study arms (presented in the Statistical Analyses sections below). In Group B, two-sided 95% Wilson CI around the single-arm estimate was specified (presented in the Data Table below).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

638 participants

Primary outcome timeframe

Week 12 in Group A 2-CpG, Week 28 in Group A 3-CpG and 3-alum and in Group B

Results posted on

2025-07-20

Participant Flow

Participants were enrolled from December 2020 to February 2023 at sites in USA and select countries in Africa, Asia and South America.

Participant milestones

Participant milestones
Measure	Group A: 2-CpG Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by intramuscular injection at Weeks 0 and 4.	Group A: 3-CpG Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by intramuscular injection at Weeks 0, 4, and 24.	Group A: 3-alum Participants were prescribed 1 mL of ENGERIX-B (conventional 3-dose hepatitis B vaccine with an aluminum hydroxide adjuvant) by intramuscular injection at Weeks 0, 4, and 24.	Group B Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by intramuscular injection at Weeks 0, 4, and 24.
Overall Study STARTED	187	189	187	75
Overall Study Eligible Participants Who Initiated Study Vaccination	187	188	186	74
Overall Study COMPLETED	176	179	176	74
Overall Study NOT COMPLETED	11	10	11	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Group A: 2-CpG Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by intramuscular injection at Weeks 0 and 4.	Group A: 3-CpG Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by intramuscular injection at Weeks 0, 4, and 24.	Group A: 3-alum Participants were prescribed 1 mL of ENGERIX-B (conventional 3-dose hepatitis B vaccine with an aluminum hydroxide adjuvant) by intramuscular injection at Weeks 0, 4, and 24.	Group B Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by intramuscular injection at Weeks 0, 4, and 24.
Overall Study Lost to Follow-up	9	7	9	0
Overall Study Withdrawal by Subject	1	2	2	0
Overall Study Death	1	1	0	0
Overall Study Protocol Violation	0	0	0	1

Baseline Characteristics

Eligible participants who initiated study vaccination series, and had anti-HBs results available at entry.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group A: 2-CpG n=187 Participants Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by intramuscular injection at Weeks 0 and 4.	Group A: 3-CpG n=188 Participants Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by intramuscular injection at Weeks 0, 4, and 24.	Group A: 3-alum n=186 Participants Participants were prescribed 1 mL of ENGERIX-B (conventional 3-dose hepatitis B vaccine with an aluminum hydroxide adjuvant) by intramuscular injection at Weeks 0, 4, and 24.	Group B n=74 Participants Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by intramuscular injection at Weeks 0, 4, and 24.	Total n=635 Participants Total of all reporting groups
Age, Customized 18-26 years	42 Participants n=187 Participants	34 Participants n=188 Participants	32 Participants n=186 Participants	4 Participants n=74 Participants	112 Participants n=635 Participants
Age, Customized 27-39 years	30 Participants n=187 Participants	35 Participants n=188 Participants	33 Participants n=186 Participants	14 Participants n=74 Participants	112 Participants n=635 Participants
Age, Customized 40-49 years	30 Participants n=187 Participants	45 Participants n=188 Participants	42 Participants n=186 Participants	30 Participants n=74 Participants	147 Participants n=635 Participants
Age, Customized 50-59 years	58 Participants n=187 Participants	53 Participants n=188 Participants	43 Participants n=186 Participants	19 Participants n=74 Participants	173 Participants n=635 Participants
Age, Customized ≥60 years	27 Participants n=187 Participants	21 Participants n=188 Participants	36 Participants n=186 Participants	7 Participants n=74 Participants	91 Participants n=635 Participants
Sex/Gender, Customized Cisgender	184 Participants n=187 Participants	181 Participants n=188 Participants	180 Participants n=186 Participants	72 Participants n=74 Participants	617 Participants n=635 Participants
Sex/Gender, Customized Transgender spectrum	3 Participants n=187 Participants	6 Participants n=188 Participants	5 Participants n=186 Participants	2 Participants n=74 Participants	16 Participants n=635 Participants
Sex/Gender, Customized Not reported	0 Participants n=187 Participants	1 Participants n=188 Participants	1 Participants n=186 Participants	0 Participants n=74 Participants	2 Participants n=635 Participants
Sex: Female, Male Female	67 Participants n=187 Participants	68 Participants n=188 Participants	67 Participants n=186 Participants	40 Participants n=74 Participants	242 Participants n=635 Participants
Sex: Female, Male Male	120 Participants n=187 Participants	120 Participants n=188 Participants	119 Participants n=186 Participants	34 Participants n=74 Participants	393 Participants n=635 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	39 Participants n=187 Participants	42 Participants n=188 Participants	40 Participants n=186 Participants	11 Participants n=74 Participants	132 Participants n=635 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	148 Participants n=187 Participants	145 Participants n=188 Participants	144 Participants n=186 Participants	63 Participants n=74 Participants	500 Participants n=635 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=187 Participants	1 Participants n=188 Participants	2 Participants n=186 Participants	0 Participants n=74 Participants	3 Participants n=635 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=187 Participants	2 Participants n=188 Participants	1 Participants n=186 Participants	0 Participants n=74 Participants	4 Participants n=635 Participants
Race/Ethnicity, Customized Asian	29 Participants n=187 Participants	35 Participants n=188 Participants	33 Participants n=186 Participants	49 Participants n=74 Participants	146 Participants n=635 Participants
Race/Ethnicity, Customized Black or African American	85 Participants n=187 Participants	76 Participants n=188 Participants	74 Participants n=186 Participants	12 Participants n=74 Participants	247 Participants n=635 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=187 Participants	0 Participants n=188 Participants	0 Participants n=186 Participants	1 Participants n=74 Participants	1 Participants n=635 Participants
Race/Ethnicity, Customized White	62 Participants n=187 Participants	62 Participants n=188 Participants	72 Participants n=186 Participants	11 Participants n=74 Participants	207 Participants n=635 Participants
Race/Ethnicity, Customized Other	2 Participants n=187 Participants	4 Participants n=188 Participants	1 Participants n=186 Participants	0 Participants n=74 Participants	7 Participants n=635 Participants
Race/Ethnicity, Customized Multiple	2 Participants n=187 Participants	1 Participants n=188 Participants	2 Participants n=186 Participants	0 Participants n=74 Participants	5 Participants n=635 Participants
Race/Ethnicity, Customized Unknown	6 Participants n=187 Participants	8 Participants n=188 Participants	3 Participants n=186 Participants	1 Participants n=74 Participants	18 Participants n=635 Participants
Region of Enrollment Vietnam	10 Participants n=187 Participants	13 Participants n=188 Participants	12 Participants n=186 Participants	0 Participants n=74 Participants	35 Participants n=635 Participants
Region of Enrollment United States	103 Participants n=187 Participants	102 Participants n=188 Participants	107 Participants n=186 Participants	20 Participants n=74 Participants	332 Participants n=635 Participants
Region of Enrollment Malawi	5 Participants n=187 Participants	5 Participants n=188 Participants	6 Participants n=186 Participants	0 Participants n=74 Participants	16 Participants n=635 Participants
Region of Enrollment Botswana	10 Participants n=187 Participants	9 Participants n=188 Participants	10 Participants n=186 Participants	0 Participants n=74 Participants	29 Participants n=635 Participants
Region of Enrollment Brazil	13 Participants n=187 Participants	13 Participants n=188 Participants	11 Participants n=186 Participants	0 Participants n=74 Participants	37 Participants n=635 Participants
Region of Enrollment South Africa	14 Participants n=187 Participants	12 Participants n=188 Participants	11 Participants n=186 Participants	6 Participants n=74 Participants	43 Participants n=635 Participants
Region of Enrollment Uganda	5 Participants n=187 Participants	5 Participants n=188 Participants	4 Participants n=186 Participants	0 Participants n=74 Participants	14 Participants n=635 Participants
Region of Enrollment Kenya	8 Participants n=187 Participants	8 Participants n=188 Participants	5 Participants n=186 Participants	0 Participants n=74 Participants	21 Participants n=635 Participants
Region of Enrollment Thailand	18 Participants n=187 Participants	17 Participants n=188 Participants	19 Participants n=186 Participants	48 Participants n=74 Participants	102 Participants n=635 Participants
Region of Enrollment Philippines	1 Participants n=187 Participants	4 Participants n=188 Participants	1 Participants n=186 Participants	0 Participants n=74 Participants	6 Participants n=635 Participants
CD4 cell count <200 cells/mm^3	6 Participants n=187 Participants	3 Participants n=188 Participants	6 Participants n=186 Participants	1 Participants n=74 Participants	16 Participants n=635 Participants
CD4 cell count 200-<350 cells/mm^3	19 Participants n=187 Participants	13 Participants n=188 Participants	11 Participants n=186 Participants	10 Participants n=74 Participants	53 Participants n=635 Participants
CD4 cell count 350-<500 cells/mm^3	35 Participants n=187 Participants	28 Participants n=188 Participants	34 Participants n=186 Participants	11 Participants n=74 Participants	108 Participants n=635 Participants
CD4 cell count ≥500 cells/mm^3	127 Participants n=187 Participants	144 Participants n=188 Participants	135 Participants n=186 Participants	52 Participants n=74 Participants	458 Participants n=635 Participants
HIV-1 RNA <40 copies/mL	175 Participants n=187 Participants	176 Participants n=188 Participants	175 Participants n=186 Participants	68 Participants n=74 Participants	594 Participants n=635 Participants
HIV-1 RNA ≥40 copies/mL	12 Participants n=187 Participants	12 Participants n=188 Participants	11 Participants n=186 Participants	5 Participants n=74 Participants	40 Participants n=635 Participants
HIV-1 RNA Indeterminate	0 Participants n=187 Participants	0 Participants n=188 Participants	0 Participants n=186 Participants	1 Participants n=74 Participants	1 Participants n=635 Participants
Diabetes status Diabetes	25 Participants n=187 Participants	23 Participants n=188 Participants	26 Participants n=186 Participants	7 Participants n=74 Participants	81 Participants n=635 Participants
Diabetes status No diabetes	162 Participants n=187 Participants	165 Participants n=188 Participants	160 Participants n=186 Participants	67 Participants n=74 Participants	554 Participants n=635 Participants
Anti-HBs <10 mIU/mL	182 Participants n=185 Participants • Eligible participants who initiated study vaccination series, and had anti-HBs results available at entry.	185 Participants n=188 Participants • Eligible participants who initiated study vaccination series, and had anti-HBs results available at entry.	182 Participants n=186 Participants • Eligible participants who initiated study vaccination series, and had anti-HBs results available at entry.	74 Participants n=74 Participants • Eligible participants who initiated study vaccination series, and had anti-HBs results available at entry.	623 Participants n=633 Participants • Eligible participants who initiated study vaccination series, and had anti-HBs results available at entry.
Anti-HBs ≥10 mIU/mL	3 Participants n=185 Participants • Eligible participants who initiated study vaccination series, and had anti-HBs results available at entry.	3 Participants n=188 Participants • Eligible participants who initiated study vaccination series, and had anti-HBs results available at entry.	4 Participants n=186 Participants • Eligible participants who initiated study vaccination series, and had anti-HBs results available at entry.	0 Participants n=74 Participants • Eligible participants who initiated study vaccination series, and had anti-HBs results available at entry.	10 Participants n=633 Participants • Eligible participants who initiated study vaccination series, and had anti-HBs results available at entry.

PRIMARY outcome

Timeframe: Week 12 in Group A 2-CpG, Week 28 in Group A 3-CpG and 3-alum and in Group B

Population: Eligible participants who initiated study vaccination series and had anti-HBs data available at the specified time point

Outcome measures

Outcome measures
Measure	Group A: 2-CpG n=174 Participants Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by intramuscular injection at Weeks 0 and 4.	Group A: 3-CpG n=169 Participants Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by intramuscular injection at Weeks 0, 4, and 24.	Group A: 3-alum n=165 Participants Participants were prescribed 1 mL of ENGERIX-B (conventional 3-dose hepatitis B vaccine with an aluminum hydroxide adjuvant) by intramuscular injection at Weeks 0, 4, and 24.	Group B n=68 Participants Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by intramuscular injection at Weeks 0, 4, and 24.
Percentage of Participants With Primary Seroprotection Response	93.1 percentage of participants In Group A, CIs are provided for comparisons between study arms only (in Statistical Analyses below), as specified in the study SAP. Group B is single-arm and CI around the estimate is provided in the Data Table.	99.4 percentage of participants In Group A, CIs are provided for comparisons between study arms only (in Statistical Analyses below), as specified in the study SAP. Group B is single-arm and CI around the estimate is provided in the Data Table.	80.6 percentage of participants In Group A, CIs are provided for comparisons between study arms only (in Statistical Analyses below), as specified in the study SAP. Group B is single-arm and CI around the estimate is provided in the Data Table.	100 percentage of participants Interval 94.7 to 100.0

PRIMARY outcome

Timeframe: From study entry to study discontinuation (Week 72 or premature discontinuation)

Population: Eligible participants who initiated study vaccination series

The protocol required reporting of (1) Grade ≥2 AEs, (2) AEs that led to a change in study treatment regardless of grade, (3) AEs meeting serious AE (SAE) definition or expedited AE (EAE) reporting requirement, (4) Grade ≥1 local and systemic injection reactions within 7 days of any study vaccine injection, (5) medically attended adverse events (MAAE) regardless of grade, and (6) potential immune-mediated AEs regardless of grade. Grading was per DAIDS AE Grading Table (Version 2.1): Grade 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening) and 5 (death). DAIDS EAE Manual (V1.0) was used. Wilson method was used for confidence intervals.

Outcome measures

Outcome measures
Measure	Group A: 2-CpG n=187 Participants Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by intramuscular injection at Weeks 0 and 4.	Group A: 3-CpG n=188 Participants Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by intramuscular injection at Weeks 0, 4, and 24.	Group A: 3-alum n=186 Participants Participants were prescribed 1 mL of ENGERIX-B (conventional 3-dose hepatitis B vaccine with an aluminum hydroxide adjuvant) by intramuscular injection at Weeks 0, 4, and 24.	Group B n=74 Participants Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by intramuscular injection at Weeks 0, 4, and 24.
Percentage of Participants With Adverse Events (AEs)	73.3 percentage of participants Interval 66.5 to 79.1	77.7 percentage of participants Interval 71.2 to 83.0	73.7 percentage of participants Interval 66.9 to 79.5	87.8 percentage of participants Interval 78.5 to 93.5

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 24, 28, 32 (Group A 3-CpG and 3-alum and Group B), 48 (Group A 3-CpG and 3-alum and Group B), 52 (Group A 2-CpG) and 72. The visit schedule differed between the study arms.

Population: Eligible participants who initiated study vaccination series, and had anti-HBs data available at the given time point

Seroprotection response (SPR) was defined as antibody titer against hepatitis B surface antigen (anti-HBs) ≥10 mIU/mL. Study visit weeks are according to protocol-specified visit windows; anti-HBs results outside visit windows were not included. These are snapshots at scheduled visits irrespective of delayed vaccinations, unlike the visits defined in Primary Outcome 1. The study was designed separately for the two study populations (Groups A and B), and the analysis was conducted separately, as prespecified in the study protocol and Statistical Analysis Plan (SAP). In Group A, two-sided 97.5% confidence intervals (CI) were specified for the SPR differences between study arms (presented in the Statistical Analyses sections below). In Group B, two-sided 95% Wilson CIs around the single-arm estimates were specified (presented in the Data Table below).

Outcome measures

Outcome measures
Measure	Group A: 2-CpG n=187 Participants Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by intramuscular injection at Weeks 0 and 4.	Group A: 3-CpG n=188 Participants Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by intramuscular injection at Weeks 0, 4, and 24.	Group A: 3-alum n=186 Participants Participants were prescribed 1 mL of ENGERIX-B (conventional 3-dose hepatitis B vaccine with an aluminum hydroxide adjuvant) by intramuscular injection at Weeks 0, 4, and 24.	Group B n=74 Participants Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by intramuscular injection at Weeks 0, 4, and 24.
Percentage of Participants With Seroprotection Response Week 8: SPR	89.1 percentage of participants In Group A, CIs are provided for comparisons between study arms only (in the Statistical Analyses below), as specified in the study SAP. Group B is single-arm and CIs around the estimates are provided in the Data Table.	90.8 percentage of participants In Group A, CIs are provided for comparisons between study arms only (in the Statistical Analyses below), as specified in the study SAP. Group B is single-arm and CIs around the estimates are provided in the Data Table.	64.2 percentage of participants In Group A, CIs are provided for comparisons between study arms only (in the Statistical Analyses below), as specified in the study SAP. Group B is single-arm and CIs around the estimates are provided in the Data Table.	87.0 percentage of participants Interval 77.0 to 93.0
Percentage of Participants With Seroprotection Response Week 28: SPR	92.6 percentage of participants In Group A, CIs are provided for comparisons between study arms only (in the Statistical Analyses below), as specified in the study SAP. Group B is single-arm and CIs around the estimates are provided in the Data Table.	99.4 percentage of participants In Group A, CIs are provided for comparisons between study arms only (in the Statistical Analyses below), as specified in the study SAP. Group B is single-arm and CIs around the estimates are provided in the Data Table.	80.0 percentage of participants In Group A, CIs are provided for comparisons between study arms only (in the Statistical Analyses below), as specified in the study SAP. Group B is single-arm and CIs around the estimates are provided in the Data Table.	100 percentage of participants Interval 94.7 to 100.0
Percentage of Participants With Seroprotection Response Week 48: SPR	—	97.6 percentage of participants In Group A, CIs are provided for comparisons between study arms only (in the Statistical Analyses below), as specified in the study SAP. Group B is single-arm and CIs around the estimates are provided in the Data Table.	65.0 percentage of participants In Group A, CIs are provided for comparisons between study arms only (in the Statistical Analyses below), as specified in the study SAP. Group B is single-arm and CIs around the estimates are provided in the Data Table.	98.6 percentage of participants Interval 92.3 to 99.7
Percentage of Participants With Seroprotection Response Week 4: SPR	66.1 percentage of participants In Group A, CIs are provided for comparisons between study arms only (in the Statistical Analyses below), as specified in the study SAP. Group B is single-arm and CIs around the estimates are provided in the Data Table.	66.7 percentage of participants In Group A, CIs are provided for comparisons between study arms only (in the Statistical Analyses below), as specified in the study SAP. Group B is single-arm and CIs around the estimates are provided in the Data Table.	51.7 percentage of participants In Group A, CIs are provided for comparisons between study arms only (in the Statistical Analyses below), as specified in the study SAP. Group B is single-arm and CIs around the estimates are provided in the Data Table.	30.1 percentage of participants Interval 20.8 to 41.4
Percentage of Participants With Seroprotection Response Week 12: SPR	93.6 percentage of participants In Group A, CIs are provided for comparisons between study arms only (in the Statistical Analyses below), as specified in the study SAP. Group B is single-arm and CIs around the estimates are provided in the Data Table.	92.9 percentage of participants In Group A, CIs are provided for comparisons between study arms only (in the Statistical Analyses below), as specified in the study SAP. Group B is single-arm and CIs around the estimates are provided in the Data Table.	66.5 percentage of participants In Group A, CIs are provided for comparisons between study arms only (in the Statistical Analyses below), as specified in the study SAP. Group B is single-arm and CIs around the estimates are provided in the Data Table.	94.4 percentage of participants Interval 86.6 to 97.8
Percentage of Participants With Seroprotection Response Week 24: SPR	95.1 percentage of participants In Group A, CIs are provided for comparisons between study arms only (in the Statistical Analyses below), as specified in the study SAP. Group B is single-arm and CIs around the estimates are provided in the Data Table.	95.0 percentage of participants In Group A, CIs are provided for comparisons between study arms only (in the Statistical Analyses below), as specified in the study SAP. Group B is single-arm and CIs around the estimates are provided in the Data Table.	61.6 percentage of participants In Group A, CIs are provided for comparisons between study arms only (in the Statistical Analyses below), as specified in the study SAP. Group B is single-arm and CIs around the estimates are provided in the Data Table.	98.5 percentage of participants Interval 92.1 to 99.7
Percentage of Participants With Seroprotection Response Week 32: SPR	—	98.8 percentage of participants In Group A, CIs are provided for comparisons between study arms only (in the Statistical Analyses below), as specified in the study SAP. Group B is single-arm and CIs around the estimates are provided in the Data Table.	74.5 percentage of participants In Group A, CIs are provided for comparisons between study arms only (in the Statistical Analyses below), as specified in the study SAP. Group B is single-arm and CIs around the estimates are provided in the Data Table.	100 percentage of participants Interval 94.7 to 100.0
Percentage of Participants With Seroprotection Response Week 52: SPR	89.5 percentage of participants In Group A, CIs are provided for comparisons between study arms only (in the Statistical Analyses below), as specified in the study SAP. Group B is single-arm and CIs around the estimates are provided in the Data Table.	—	—	—
Percentage of Participants With Seroprotection Response Week 72: SPR	86.1 percentage of participants In Group A, CIs are provided for comparisons between study arms only (in the Statistical Analyses below), as specified in the study SAP. Group B is single-arm and CIs around the estimates are provided in the Data Table.	96.9 percentage of participants In Group A, CIs are provided for comparisons between study arms only (in the Statistical Analyses below), as specified in the study SAP. Group B is single-arm and CIs around the estimates are provided in the Data Table.	57.5 percentage of participants In Group A, CIs are provided for comparisons between study arms only (in the Statistical Analyses below), as specified in the study SAP. Group B is single-arm and CIs around the estimates are provided in the Data Table.	97.2 percentage of participants Interval 90.3 to 99.2

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 24, 28, 32 (Group A 3-CpG and 3-alum and Group B), 48 (Group A 3-CpG and 3-alum and Group B), 52 (Group A 2-CpG) and 72. The visit schedule differed between the study arms.

Population: Eligible participants who initiated study vaccination series, and had anti-HBs data available at the given time point

Count of participants by antibody titer against hepatitis B surface antigen (anti-HBs), categorized using cutoffs at 5, 10, 100 and 1000 mIU/mL. The testing assay lower limit of quantitation was 5 mIU/mL and upper limit 1000 mIU/mL. Study visit weeks are according to protocol-specified visit windows; anti-HBs results outside visit windows were not included. Because high proportions of participants achieved anti-HBs above the assay upper limit of quantitation, the planned geometric mean analysis was not conducted. Instead, anti-HBs were summarized according to the categories shown in the Data Table below.

Outcome measures

Outcome measures
Measure	Group A: 2-CpG n=187 Participants Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by intramuscular injection at Weeks 0 and 4.	Group A: 3-CpG n=188 Participants Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by intramuscular injection at Weeks 0, 4, and 24.	Group A: 3-alum n=186 Participants Participants were prescribed 1 mL of ENGERIX-B (conventional 3-dose hepatitis B vaccine with an aluminum hydroxide adjuvant) by intramuscular injection at Weeks 0, 4, and 24.	Group B n=74 Participants Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by intramuscular injection at Weeks 0, 4, and 24.
Count of Participants by Anti-HBs Titer Categories Week 12: anti-HBs · <5 mIU/mL	8 Participants	6 Participants	47 Participants	4 Participants
Count of Participants by Anti-HBs Titer Categories Week 12: anti-HBs · 10-99 mIU/mL	39 Participants	38 Participants	42 Participants	19 Participants
Count of Participants by Anti-HBs Titer Categories Week 24: anti-HBs · >1000 mIU/mL	38 Participants	49 Participants	9 Participants	19 Participants
Count of Participants by Anti-HBs Titer Categories Week 32: anti-HBs · 5-9 mIU/mL	—	0 Participants	10 Participants	0 Participants
Count of Participants by Anti-HBs Titer Categories Week 4: anti-HBs · <5 mIU/mL	47 Participants	52 Participants	80 Participants	46 Participants
Count of Participants by Anti-HBs Titer Categories Week 4: anti-HBs · 5-9 mIU/mL	13 Participants	7 Participants	4 Participants	5 Participants
Count of Participants by Anti-HBs Titer Categories Week 4: anti-HBs · 10-99 mIU/mL	34 Participants	46 Participants	36 Participants	10 Participants
Count of Participants by Anti-HBs Titer Categories Week 4: anti-HBs · 100-1000 mIU/mL	65 Participants	49 Participants	36 Participants	8 Participants
Count of Participants by Anti-HBs Titer Categories Week 4: anti-HBs · >1000 mIU/mL	18 Participants	23 Participants	18 Participants	4 Participants
Count of Participants by Anti-HBs Titer Categories Week 8: anti-HBs · <5 mIU/mL	16 Participants	9 Participants	52 Participants	7 Participants
Count of Participants by Anti-HBs Titer Categories Week 8: anti-HBs · 5-9 mIU/mL	3 Participants	7 Participants	10 Participants	2 Participants
Count of Participants by Anti-HBs Titer Categories Week 8: anti-HBs · 10-99 mIU/mL	33 Participants	37 Participants	36 Participants	24 Participants
Count of Participants by Anti-HBs Titer Categories Week 8: anti-HBs · 100-1000 mIU/mL	72 Participants	68 Participants	46 Participants	28 Participants
Count of Participants by Anti-HBs Titer Categories Week 8: anti-HBs · >1000 mIU/mL	51 Participants	53 Participants	29 Participants	8 Participants
Count of Participants by Anti-HBs Titer Categories Week 12: anti-HBs · 5-9 mIU/mL	3 Participants	6 Participants	9 Participants	0 Participants
Count of Participants by Anti-HBs Titer Categories Week 12: anti-HBs · 100-1000 mIU/mL	76 Participants	71 Participants	50 Participants	38 Participants
Count of Participants by Anti-HBs Titer Categories Week 12: anti-HBs · >1000 mIU/mL	46 Participants	48 Participants	19 Participants	11 Participants
Count of Participants by Anti-HBs Titer Categories Week 24: anti-HBs · <5 mIU/mL	6 Participants	5 Participants	50 Participants	1 Participants
Count of Participants by Anti-HBs Titer Categories Week 24: anti-HBs · 5-9 mIU/mL	2 Participants	3 Participants	13 Participants	0 Participants
Count of Participants by Anti-HBs Titer Categories Week 24: anti-HBs · 10-99 mIU/mL	31 Participants	27 Participants	50 Participants	14 Participants
Count of Participants by Anti-HBs Titer Categories Week 24: anti-HBs · 100-1000 mIU/mL	85 Participants	79 Participants	42 Participants	34 Participants
Count of Participants by Anti-HBs Titer Categories Week 28: anti-HBs · <5 mIU/mL	6 Participants	1 Participants	25 Participants	0 Participants
Count of Participants by Anti-HBs Titer Categories Week 28: anti-HBs · 5-9 mIU/mL	6 Participants	0 Participants	7 Participants	0 Participants
Count of Participants by Anti-HBs Titer Categories Week 28: anti-HBs · 10-99 mIU/mL	29 Participants	6 Participants	28 Participants	2 Participants
Count of Participants by Anti-HBs Titer Categories Week 28: anti-HBs · 100-1000 mIU/mL	81 Participants	28 Participants	43 Participants	9 Participants
Count of Participants by Anti-HBs Titer Categories Week 28: anti-HBs · >1000 mIU/mL	41 Participants	127 Participants	57 Participants	57 Participants
Count of Participants by Anti-HBs Titer Categories Week 32: anti-HBs · <5 mIU/mL	—	2 Participants	31 Participants	0 Participants
Count of Participants by Anti-HBs Titer Categories Week 32: anti-HBs · 10-99 mIU/mL	—	8 Participants	27 Participants	2 Participants
Count of Participants by Anti-HBs Titer Categories Week 32: anti-HBs · 100-1000 mIU/mL	—	39 Participants	47 Participants	11 Participants
Count of Participants by Anti-HBs Titer Categories Week 32: anti-HBs · >1000 mIU/mL	—	112 Participants	46 Participants	56 Participants
Count of Participants by Anti-HBs Titer Categories Week 48: anti-HBs · <5 mIU/mL	—	3 Participants	45 Participants	0 Participants
Count of Participants by Anti-HBs Titer Categories Week 48: anti-HBs · 5-9 mIU/mL	—	1 Participants	11 Participants	1 Participants
Count of Participants by Anti-HBs Titer Categories Week 48: anti-HBs · 10-99 mIU/mL	—	15 Participants	32 Participants	5 Participants
Count of Participants by Anti-HBs Titer Categories Week 48: anti-HBs · 100-1000 mIU/mL	—	70 Participants	48 Participants	25 Participants
Count of Participants by Anti-HBs Titer Categories Week 48: anti-HBs · >1000 mIU/mL	—	79 Participants	24 Participants	39 Participants
Count of Participants by Anti-HBs Titer Categories Week 52: anti-HBs · <5 mIU/mL	12 Participants	—	—	—
Count of Participants by Anti-HBs Titer Categories Week 52: anti-HBs · 5-9 mIU/mL	5 Participants	—	—	—
Count of Participants by Anti-HBs Titer Categories Week 52: anti-HBs · 10-99 mIU/mL	39 Participants	—	—	—
Count of Participants by Anti-HBs Titer Categories Week 52: anti-HBs · 100-1000 mIU/mL	84 Participants	—	—	—
Count of Participants by Anti-HBs Titer Categories Week 52: anti-HBs · >1000 mIU/mL	22 Participants	—	—	—
Count of Participants by Anti-HBs Titer Categories Week 72: anti-HBs · <5 mIU/mL	16 Participants	5 Participants	53 Participants	1 Participants
Count of Participants by Anti-HBs Titer Categories Week 72: anti-HBs · 5-9 mIU/mL	6 Participants	0 Participants	12 Participants	1 Participants
Count of Participants by Anti-HBs Titer Categories Week 72: anti-HBs · 10-99 mIU/mL	45 Participants	25 Participants	32 Participants	10 Participants
Count of Participants by Anti-HBs Titer Categories Week 72: anti-HBs · 100-1000 mIU/mL	77 Participants	76 Participants	39 Participants	32 Participants
Count of Participants by Anti-HBs Titer Categories Week 72: anti-HBs · >1000 mIU/mL	15 Participants	55 Participants	17 Participants	27 Participants

SECONDARY outcome

Timeframe: From study vaccination initiation to 4 weeks after last study vaccination (Week 8 in Group A 2-CpG, Week 28 in Group A 3-CpG and 3-alum and Group B)

Population: Eligible participants who initiated study vaccination series

The protocol required reporting of (1) Grade ≥2 AEs, (2) AEs that led to a change in study treatment regardless of grade, (3) AEs meeting serious AE (SAE) definition or expedited AE (EAE) reporting requirement, (4) Grade ≥1 local and systemic injection reactions within 7 days of any study vaccine injection, (5) medically attended adverse events (MAAE) regardless of grade, and (6) potential immune-mediated AEs regardless of grade. This outcome is limited to the Grade ≥2 AEs that occurred within 4 weeks after any study vaccination. Grading was per DAIDS AE Grading Table (Version 2.1): Grade 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening) and 5 (death). DAIDS EAE Manual (V1.0) was used. Wilson method was used for confidence intervals.

Outcome measures

Outcome measures
Measure	Group A: 2-CpG n=187 Participants Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by intramuscular injection at Weeks 0 and 4.	Group A: 3-CpG n=188 Participants Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by intramuscular injection at Weeks 0, 4, and 24.	Group A: 3-alum n=186 Participants Participants were prescribed 1 mL of ENGERIX-B (conventional 3-dose hepatitis B vaccine with an aluminum hydroxide adjuvant) by intramuscular injection at Weeks 0, 4, and 24.	Group B n=74 Participants Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by intramuscular injection at Weeks 0, 4, and 24.
Percentage of Participants With Grade ≥2 AEs Post-vaccination Adverse Events	33.7 percentage of participants Interval 27.3 to 40.7	45.7 percentage of participants Interval 38.8 to 52.9	43.5 percentage of participants Interval 36.6 to 50.7	48.6 percentage of participants Interval 37.6 to 59.8

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 12 in Group A 2-CpG, Week 28 in Group A 3-CpG and 3-alum and in Group B

Population: Eligible participants who initiated study vaccination series and had anti-HBs data available at the specified time point

Subgroup analysis of the primary seroprotection response outcome measure (as described in the Primary Outcome Measure 1 above) by sex. Descriptive summary of the SPR by subgroups; the study was not powered for testing the success of HEPLISAV-B vaccination within subgroups.

Outcome measures

Outcome measures
Measure	Group A: 2-CpG n=174 Participants Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by intramuscular injection at Weeks 0 and 4.	Group A: 3-CpG n=169 Participants Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by intramuscular injection at Weeks 0, 4, and 24.	Group A: 3-alum n=165 Participants Participants were prescribed 1 mL of ENGERIX-B (conventional 3-dose hepatitis B vaccine with an aluminum hydroxide adjuvant) by intramuscular injection at Weeks 0, 4, and 24.	Group B n=68 Participants Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by intramuscular injection at Weeks 0, 4, and 24.
Percentage of Participants With Primary Seroprotection Response by Sex Among females	98.4 percentage of participants	98.5 percentage of participants	89.7 percentage of participants	100 percentage of participants
Percentage of Participants With Primary Seroprotection Response by Sex Among males	90.0 percentage of participants	100 percentage of participants	75.7 percentage of participants	100 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 12 in Group A 2-CpG, Week 28 in Group A 3-CpG and 3-alum and in Group B

Population: Eligible participants who initiated study vaccination series and had anti-HBs data available at the specified time point

Subgroup analysis of the primary seroprotection response outcome measure (as described in the Primary Outcome Measure 1 above) by race. Descriptive summary of the SPR by subgroups; the study was not powered for testing the success of HEPLISAV-B vaccination within subgroups.

Outcome measures

Outcome measures
Measure	Group A: 2-CpG n=174 Participants Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by intramuscular injection at Weeks 0 and 4.	Group A: 3-CpG n=169 Participants Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by intramuscular injection at Weeks 0, 4, and 24.	Group A: 3-alum n=165 Participants Participants were prescribed 1 mL of ENGERIX-B (conventional 3-dose hepatitis B vaccine with an aluminum hydroxide adjuvant) by intramuscular injection at Weeks 0, 4, and 24.	Group B n=68 Participants Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by intramuscular injection at Weeks 0, 4, and 24.
Percentage of Participants With Primary Seroprotection Response by Race Among Black race	97.5 percentage of participants	100 percentage of participants	92.3 percentage of participants	100 percentage of participants
Percentage of Participants With Primary Seroprotection Response by Race Among White race	90.7 percentage of participants	98.0 percentage of participants	67.7 percentage of participants	100 percentage of participants
Percentage of Participants With Primary Seroprotection Response by Race Among Other or Unknown race	63.6 percentage of participants	100 percentage of participants	100 percentage of participants	100 percentage of participants
Percentage of Participants With Primary Seroprotection Response by Race Among Asian race	96.4 percentage of participants	100 percentage of participants	80.0 percentage of participants	100 percentage of participants

Adverse Events

Group A: 2-CpG

Serious events: 12 serious events

Other events: 133 other events

Deaths: 1 deaths

Group A: 3-CpG

Serious events: 15 serious events

Other events: 146 other events

Deaths: 1 deaths

Group A: 3-alum

Serious events: 11 serious events

Other events: 134 other events

Deaths: 0 deaths

Group B

Serious events: 4 serious events

Other events: 64 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

ACTG Clinicaltrials.gov Coordinator

ACTG Network Coordinating Center, Social and Scientific Systems, a DLH Holdings Company

Phone: (301) 628-3348

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER